Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted globally. The aim of this trial is to investigate Efficacy and Safety of Oral Semaglutide versus Empagliflozin in Subjects with Type 2 Diabetes Mellitus.
Interventions
DRUGsemaglutide
Oral administration once-daily.
DRUGempagliflozin
Oral administration once-daily.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial * Male or female, age above or equal to 18 years at the time of signing informed consent * Diagnosed with type 2 diabetes mellitus at least 90 days prior to day of screening * HbA1c (glycosylated haemoglobin) of 7.0-10.5 % (53-91 mmol/mol) (both inclusive) * Stable daily dose of metformin (at least 1500 mg or maximum tolerated dose as documented in the subject medical record) at least 90 days prior to the day of screening
Exclusion criteria
* Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice).For certain specific countries: Additional specific requirements apply * Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol * Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma * History of pancreatitis (acute or chronic) * History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery) * Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening * Subjects presently classified as being in New York Heart Association Class IV * Planned coronary, carotid or peripheral artery revascularisation known on the day of screening * Subjects with ALT (alanine aminotransferase) above 2.5 x upper normal limit * Renal impairment defined as Estimated Glomerular Filtration Rate below 60 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) * Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of below or equal to 14 days * Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation * History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ) * History of diabetic ketoacidosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c | Week 0, week 26 | Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c (%) | Week 0, week 52 | Change from baseline (week 0) in HbA1c was evaluated at week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Body Weight (kg) | Week 0, week 52 | Change from baseline (week 0) in body weight was evaluated at week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Fasting Plasma Glucose | Week 0, week 26, week 52 | Change from baseline (week 0) in fasting plasma glucose was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in SMPG : Mean of the 7-point Profile | Week 0, week 26 and week 52 | Change from baseline (week 0) in mean of the 7-point self-measured plasma glucose (SMPG) (i.e. before and after breakfast, lunch and dinner, and at bedtime) profile was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in SMPG : Mean Postprandial Increment Over All Meals | Week 0, week 26 and week 52 | Change from baseline (week 0) in mean postprandial glucose increment was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Fasting C-peptide (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in fasting C-peptide (Nanomoles per liter \[nmol/L\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Fasting Insulin (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in fasting insulin (picomoles per liter \[pmol/L\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Fasting Pro-insulin (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in fasting pro-insulin (pmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Fasting Glucagon (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in fasting glucagon (picograms per milliliter \[pg/mL\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in HOMA-IR (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in homeostatic model assessment index of insulin resistance (HOMA-IR) (%) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in HOMA-B (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in homeostatic model assessment index of beta-cell function (HOMA-B) (%) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in C-reactive Protein (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in C-reactive protein (milligrams per liter \[mg/L\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Body Weight (%) | Week 0, week 26, week 52 | Relative change from baseline (week 0) in body weight (kg) was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Body Mass Index | Week 0, week 26, week 52 | Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Waist Circumference | Week 0, week 26, week 52 | Change from baseline (week 0) in waist circumference was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Fasting Total Cholesterol (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in fasting total cholesterol (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Fasting LDL Cholesterol (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in fasting low density lipoprotein (LDL) cholesterol (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Fasting HDL Cholesterol (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in fasting high density lipoprotein (HDL) cholesterol (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Fasting VLDL Cholesterol (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in fasting very low density lipoprotein (VLDL) cholesterol (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Fasting Free Fatty Acids (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in fasting free fatty acids (FFA) (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. Because of an issue with the handling of the blood samples for FFA, all FFA data are considered invalid for this trial; thus, no conclusion with regards to FFA levels can be made based on the FFA data. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Fasting Triglycerides (Ratio to Baseline) | Week 0, week 26 and week 52 | Change from baseline (week 0) in fasting triglycerides (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) | Week 26 and week 52 | Participants who achieved HbA1c \<7.0% (53 mmol/mol) (American Diabetes Association (ADA) target) at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | Week 26 and week 52 | Participants who achieved HbA1c ≤6.5% (48 mmol/mol) (American Association of Clinical Endocrinologists (AACE) target) at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Participants Who Achieve Weight Loss ≥5% (Yes/no) | Week 26 and week 52 | Participants who achieved weight loss of ≥5% at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Participants Who Achieve Weight Loss ≥10% (Yes/no) | Week 26 and week 52 | Participants who achieved weight loss of ≥10% at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) | Week 26 and week 52 | Participants who achieved HbA1c \<7.0% (53 mmol/mol) without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain at week 26 and week 52. Severe or BG-confirmed symptomatic hypoglycaemia: an episode, that is severe according to the ADA classification or BG-confirmed by a plasma glucose value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | Week 26 and week 52 | Participants who achieved HbA1c reduction ≥1%-point and weight loss of ≥3% at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Time to Additional Anti-diabetic Medication | Weeks 0-52 | Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Additional anti-diabetic medication: use of new anti-diabetic medication for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 26/week 52), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Time to Rescue Medication | Weeks 0-52 | Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Rescue medication: use of new antidiabetic medication as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 0) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period: the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication. |
| Number of Treatment-emergent Adverse Events (TEAE) | Weeks 0-57 | A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) with onset in the on-treatment observation period (the time period where participants are considered treated with trial product) and was assessed up to approximately 57 weeks (52-week treatment period plus the 5-week follow-up period). |
| Change in Amylase (Ratio to Baseline) | Week 0, week 26, week 52 | Change from baseline (week 0) in amylase (units per liter \[U/L\]) at week 26 and week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
| Change in Lipase (Ratio to Baseline) | Week 0, week 26, week 52 | Change from baseline (week 0) in lipase (U/L) at week 26 and week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
| Change in Pulse Rate | Week 0, week 26, week 52 | Change from baseline (week 0) in pulse rate was evaluated at week 26 and week 52. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
| Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | Week 0, week 26, week 52 | Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 26 and week 52. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
| Change in ECG | Week 0, week 26, week 52 | Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at week 26 and week 52. Change from baseline results are presented as shift in findings (normal, abnormal and not clinically significant (NCS), and abnormal and clinically significant (CS)) from week 0 to week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Physical Examination | Week -2, week 52 | The physical examination findings (normal, abnormal NCS and abnormal CS) of the participants at week -2 and week 52 are presented for the following examinations: Cardiovascular system, Nervous system (central and peripheral); Gastrointestinal system, incl. mouth; General appearance; Head (ears, eyes, nose), throat, neck; Lymph node palpation; Musculoskeletal system; Respiratory system; Skin; Thyroid gland. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Eye Examination | Week -2, week 52 | The eye examination findings (normal, abnormal NCS and abnormal CS) of the participants at baseline (week -2) and week 52 are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Occurrence of Anti-semaglutide Binding Antibodies (Yes/no) | Weeks 0-57 | This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide binding antibodies anytime during post-baseline visits (week 0 to week 57) are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no) | Weeks 0-57 | This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide neutralising antibodies anytime during post-baseline visits (week 0 to week 57) are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no) | Weeks 0-57 | This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide binding antibodies cross reacting with native glucagon-like peptide-1 (GLP-1) anytime during post-baseline visits (week 0 to week 57) are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no) | Weeks 0-57 | This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide neutralising antibodies cross reacting with native GLP-1 anytime during post-baseline visits (week 0 to week 57) are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Anti-semaglutide Binding Antibody Levels | Weeks 0-57 | This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. It is based on the data from participants who were measured with anti-semaglutide antibodies anytime during post-baseline visits (week 0 to week 57). Results are presented as percentage of bound radioactivity-labelled semaglutide /total added radioactivity-labelled semaglutide (%B/T). The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. |
| Change in Body Weight (Kg) | Week 0, week 26 | Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication. |
| Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no) | Weeks 0-57 | Number of participants with treatment-emergent severe or BG-confirmed symptomatic hypoglycaemic episodes was recorded during week 0-57. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
| Semaglutide Plasma Concentrations for Population PK Analyses | Weeks 0-52 | Semaglutide plasma concentrations were measured after 25 minutes post-dose at week 4, 26 and 52. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
| SNAC Plasma Concentrations | Weeks 0-52 | This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Sodium N-\[8-(2-hydroxybenzoyl) amino\]caprylate (SNAC) plasma concentrations were measured after 25 and 40 minutes post-dose at week 4, 26 and 52. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
| Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 0, week 26, week 52 | SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at weeks 26 and 52. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period. |
| Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 0, week 26, week 52 | Change from baseline (week 0) in Control of Eating Questionnaire (CoEQ) was evaluated at weeks 26 and 52. The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control' (items 9-12, 19), 'positive mood' (items 5-8), 'craving for savoury' (items 4, 16-18) and 'craving for sweet' (items 3, 13-15). The 19 items were scored on an 11-point graded response scale ranging from 10 to 0, with items relating to each of the 4 domains being averaged to create a final score. A low score in the domains 'craving for sweet and 'craving for savoury' represents a low level of craving; whereas a high score in the domains 'craving control' and 'positive mood' represents good control and a good mood, respectively. Results are based on the data from the in-trial observation period. |
| Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-57 | Treatment-emergent hypoglycaemia is an episode with onset in the on-treatment observation period (the time period where participants are considered treated with trial product) and was assessed up to approximately 57 weeks (52-week treatment period plus the 5-week follow-up period). Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
Countries
Argentina, Brazil, Croatia, Greece, Hungary, Italy, Poland, Russia, Serbia, Spain, Thailand, United States
Participant flow
Recruitment details
The trial was conducted at 108 sites in 12 countries as follows: Argentina (4), Brazil (3), Croatia (4), Greece (7), Hungary (7), Italy (5), Poland (6), Russian Federation (6), Serbia (5), Spain (8), Thailand (3), United States (46). 1 site each in Croatia and Italy, and 2 sites in the United States screened, but didn't randomise any subjects.
Pre-assignment details
Data presented in participant flow is based on the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Participants by arm
| Arm | Count |
|---|---|
| Oral Semaglutide 14 mg Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52). | 411 |
| Empagliflozin 25 mg Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52. | 410 |
| Total | 821 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Died | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 10 |
| Overall Study | Withdrawal by Subject | 7 | 12 |
Baseline characteristics
| Characteristic | Empagliflozin 25 mg | Total | Oral Semaglutide 14 mg |
|---|---|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 10 | 58 years STANDARD_DEVIATION 10 | 57 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 108 Participants | 199 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 302 Participants | 622 Participants | 320 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HbA1c | 8.1 percentage of HbA1c STANDARD_DEVIATION 0.9 | 8.1 percentage of HbA1c STANDARD_DEVIATION 0.9 | 8.1 percentage of HbA1c STANDARD_DEVIATION 0.9 |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 21 Participants | 49 Participants | 28 Participants |
| Race/Ethnicity, Customized Race Black or African American | 33 Participants | 59 Participants | 26 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 353 Participants | 708 Participants | 355 Participants |
| Sex: Female, Male Female | 201 Participants | 406 Participants | 205 Participants |
| Sex: Female, Male Male | 209 Participants | 415 Participants | 206 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 410 | 1 / 409 |
| other Total, other adverse events | 128 / 410 | 44 / 409 |
| serious Total, serious adverse events | 27 / 410 | 37 / 409 |
Outcome results
Primary
Change in HbA1c
Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in HbA1c | In-trial | -1.3 Percentage-point of HbA1c | Standard Deviation 1.1 |
| Oral Semaglutide 14 mg | Change in HbA1c | On-treatment without rescue medication | -1.5 Percentage-point of HbA1c | Standard Deviation 1.1 |
| Empagliflozin 25 mg | Change in HbA1c | In-trial | -0.9 Percentage-point of HbA1c | Standard Deviation 0.9 |
| Empagliflozin 25 mg | Change in HbA1c | On-treatment without rescue medication | -0.9 Percentage-point of HbA1c | Standard Deviation 0.9 |
Comparison: The analysis was based on a pattern mixture model using multiple imputation to handle missing week 26 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using an analysis of covariance (ANCOVA) model with treatment and region as categorical fixed effects and baseline HbA1c value as covariate for each of the 1000 imputed complete data sets, and pooled by Rubin's rule to draw inference.p-value: <0.000195% CI: [-0.6, -0.3]Pattern mixture model
Comparison: The analysis was based on a pattern mixture model using multiple imputation to handle missing week 26 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using an ANCOVA model with treatment and region as categorical fixed effects and baseline HbA1c value as covariate for each of the 1000 imputed complete data sets, and pooled by Rubin's rule to draw inference.p-value: <0.000195% CI: [-0.6, -0.3]Pattern mixture model
Comparison: The analysis was based on a mixed model for repeated measurements (MMRM) that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 26. The independent effects were treatment and region as categorical fixed effects and the baseline HbA1c value as a covariate, all nested within visit, and an unstructured residual covariance matrix.p-value: <0.000195% CI: [-0.7, -0.4]MMRM
Comparison: The analysis was based on a MMRM that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 26. The independent effects were treatment and region as categorical fixed effects and the baseline HbA1c value as a covariate, all nested within visit, and an unstructured residual covariance matrix.p-value: <0.000195% CI: [-0.7, -0.4]MMRM
Secondary
Anti-semaglutide Binding Antibody Levels
This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. It is based on the data from participants who were measured with anti-semaglutide antibodies anytime during post-baseline visits (week 0 to week 57). Results are presented as percentage of bound radioactivity-labelled semaglutide /total added radioactivity-labelled semaglutide (%B/T). The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Weeks 0-57
Population: Overall number of participants analysed = participants who were found positive for anti-semaglutide antibodies.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Anti-semaglutide Binding Antibody Levels | Week 4 | 2.75 %B/T | Standard Deviation 0 |
| Oral Semaglutide 14 mg | Anti-semaglutide Binding Antibody Levels | Week 8 | 2.17 %B/T | Standard Deviation 0 |
Secondary
Change in Amylase (Ratio to Baseline)
Change from baseline (week 0) in amylase (units per liter \[U/L\]) at week 26 and week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Week 0, week 26, week 52
Population: Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Amylase (Ratio to Baseline) | Week 52 | 1.13 Ratio of amylase | Geometric Coefficient of Variation 31.5 |
| Oral Semaglutide 14 mg | Change in Amylase (Ratio to Baseline) | Week 26 | 1.15 Ratio of amylase | Geometric Coefficient of Variation 30.1 |
| Empagliflozin 25 mg | Change in Amylase (Ratio to Baseline) | Week 26 | 1.10 Ratio of amylase | Geometric Coefficient of Variation 24.8 |
| Empagliflozin 25 mg | Change in Amylase (Ratio to Baseline) | Week 52 | 1.11 Ratio of amylase | Geometric Coefficient of Variation 26.8 |
Secondary
Change in Blood Pressure (Systolic and Diastolic Blood Pressure)
Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 26 and week 52. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Week 0, week 26, week 52
Population: Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | SBP, week 26 | -5 Millimeters of mercury (mmHg) | Standard Deviation 15 |
| Oral Semaglutide 14 mg | Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | SBP, week 52 | -5 Millimeters of mercury (mmHg) | Standard Deviation 13 |
| Oral Semaglutide 14 mg | Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | DBP, week 26 | -2 Millimeters of mercury (mmHg) | Standard Deviation 9 |
| Oral Semaglutide 14 mg | Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | DBP, week 52 | -3 Millimeters of mercury (mmHg) | Standard Deviation 10 |
| Empagliflozin 25 mg | Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | DBP, week 52 | -3 Millimeters of mercury (mmHg) | Standard Deviation 9 |
| Empagliflozin 25 mg | Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | SBP, week 26 | -5 Millimeters of mercury (mmHg) | Standard Deviation 14 |
| Empagliflozin 25 mg | Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | DBP, week 26 | -3 Millimeters of mercury (mmHg) | Standard Deviation 9 |
| Empagliflozin 25 mg | Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | SBP, week 52 | -4 Millimeters of mercury (mmHg) | Standard Deviation 15 |
Secondary
Change in Body Mass Index
Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26, week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Body Mass Index | Week 26 | -1.4 Kilograms per square meter (kg/m^2) | Standard Deviation 1.6 |
| Oral Semaglutide 14 mg | Change in Body Mass Index | Week 52 | -1.5 Kilograms per square meter (kg/m^2) | Standard Deviation 2 |
| Empagliflozin 25 mg | Change in Body Mass Index | Week 26 | -1.4 Kilograms per square meter (kg/m^2) | Standard Deviation 1.4 |
| Empagliflozin 25 mg | Change in Body Mass Index | Week 52 | -1.4 Kilograms per square meter (kg/m^2) | Standard Deviation 1.6 |
Secondary
Change in Body Weight (%)
Relative change from baseline (week 0) in body weight (kg) was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26, week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Body Weight (%) | Week 26 | -4.34 Percentage change | Standard Deviation 4.51 |
| Oral Semaglutide 14 mg | Change in Body Weight (%) | Week 52 | -4.38 Percentage change | Standard Deviation 5.76 |
| Empagliflozin 25 mg | Change in Body Weight (%) | Week 26 | -4.14 Percentage change | Standard Deviation 4.12 |
| Empagliflozin 25 mg | Change in Body Weight (%) | Week 52 | -4.09 Percentage change | Standard Deviation 4.78 |
Secondary
Change in Body Weight (kg)
Change from baseline (week 0) in body weight was evaluated at week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Body Weight (kg) | -4.0 Kg | Standard Deviation 5.5 |
| Empagliflozin 25 mg | Change in Body Weight (kg) | -3.7 Kg | Standard Deviation 4.3 |
Secondary
Change in Body Weight (Kg)
Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Body Weight (Kg) | In-trial | -3.9 Kilogram (Kg) | Standard Deviation 4.4 |
| Oral Semaglutide 14 mg | Change in Body Weight (Kg) | On-treatment without rescue medication | -4.3 Kilogram (Kg) | Standard Deviation 4.4 |
| Empagliflozin 25 mg | Change in Body Weight (Kg) | In-trial | -3.8 Kilogram (Kg) | Standard Deviation 3.8 |
| Empagliflozin 25 mg | Change in Body Weight (Kg) | On-treatment without rescue medication | -3.9 Kilogram (Kg) | Standard Deviation 3.8 |
Comparison: The analysis was based on a pattern mixture model using multiple imputation to handle missing week 26 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using an ANCOVA model with treatment and region as categorical fixed effects and baseline body weight value as covariate for each of the 1000 imputed complete data sets, and pooled by Rubin's rule to draw inference.p-value: =0.759395% CI: [-0.7, 0.5]Pattern mixture model
Comparison: The analysis was based on a MMRM that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 26. The independent effects were treatment and region as categorical fixed effects and the baseline body weight value as a covariate, all nested within visit, and an unstructured residual covariance matrix.p-value: =0.135895% CI: [-1, 0.1]MMRM
Secondary
Change in CoEQ: Scores From the 4 Domains and the 19 Items
Change from baseline (week 0) in Control of Eating Questionnaire (CoEQ) was evaluated at weeks 26 and 52. The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control' (items 9-12, 19), 'positive mood' (items 5-8), 'craving for savoury' (items 4, 16-18) and 'craving for sweet' (items 3, 13-15). The 19 items were scored on an 11-point graded response scale ranging from 10 to 0, with items relating to each of the 4 domains being averaged to create a final score. A low score in the domains 'craving for sweet and 'craving for savoury' represents a low level of craving; whereas a high score in the domains 'craving control' and 'positive mood' represents good control and a good mood, respectively. Results are based on the data from the in-trial observation period.
Time frame: Week 0, week 26, week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 8.Feeling of contentment | 0.23 Score on a scale | Standard Deviation 2.54 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 3.Desire to eat sweet foods | -0.35 Score on a scale | Standard Deviation 3.04 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 9.Food cravings during 7 days | -0.43 Score on a scale | Standard Deviation 3.25 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: Positive Mood | 0.08 Score on a scale | Standard Deviation 1.52 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 9.Food cravings during 7 days | -0.42 Score on a scale | Standard Deviation 3.23 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 3.Desire to eat sweet foods | -0.36 Score on a scale | Standard Deviation 3.23 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 10.Strength of food cravings | -0.27 Score on a scale | Standard Deviation 3.11 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: Craving for Sweet | -0.21 Score on a scale | Standard Deviation 2.23 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 10.Strength of food cravings | -0.32 Score on a scale | Standard Deviation 3.13 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 4.Desire to eat savoury foods | -0.82 Score on a scale | Standard Deviation 2.99 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 11.Difficulty to resist food cravings | -0.47 Score on a scale | Standard Deviation 3.41 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: Craving for Savoury | -0.68 Score on a scale | Standard Deviation 2.13 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 11.Difficulty to resist food cravings | -0.33 Score on a scale | Standard Deviation 3.26 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 4.Desire to eat savoury foods | -0.82 Score on a scale | Standard Deviation 3.15 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 12.Eating in response to food cravings | -0.19 Score on a scale | Standard Deviation 2.94 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 1.Feeling of hunger | -0.80 Score on a scale | Standard Deviation 2.69 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 12.Eating in response to food cravings | -0.17 Score on a scale | Standard Deviation 2.97 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 5.Feeling of happiness | 0.00 Score on a scale | Standard Deviation 2.24 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 13.Cravings for chocolate | -0.10 Score on a scale | Standard Deviation 3.03 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: Craving control | 0.44 Score on a scale | Standard Deviation 2.54 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 13.Cravings for chocolate | 0.08 Score on a scale | Standard Deviation 3.13 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 5.Feeling of happiness | 0.13 Score on a scale | Standard Deviation 2.61 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 14.Cravings for other sweet foods | -0.39 Score on a scale | Standard Deviation 2.91 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 1.Feeling of hunger | -0.60 Score on a scale | Standard Deviation 2.82 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 14.Cravings for other sweet foods | -0.33 Score on a scale | Standard Deviation 2.9 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 6.Feeling of anxiousness | -0.21 Score on a scale | Standard Deviation 2.92 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 15.Cravings for fruit or fruit juice | -0.15 Score on a scale | Standard Deviation 3.29 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: Craving for Savoury | -0.66 Score on a scale | Standard Deviation 2.16 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 15.Cravings for fruit or fruit juice | -0.22 Score on a scale | Standard Deviation 3.31 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 6.Feeling of anxiousness | -0.19 Score on a scale | Standard Deviation 3.03 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 16.Cravings for dairy foods | -0.48 Score on a scale | Standard Deviation 3.05 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 2.Feeling of fullness | 0.40 Score on a scale | Standard Deviation 2.65 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 16.Cravings for dairy foods | -0.42 Score on a scale | Standard Deviation 3.11 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 7.Feeling of alertness | 0.01 Score on a scale | Standard Deviation 2.68 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 17.Cravings for starchy foods | -0.81 Score on a scale | Standard Deviation 2.99 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: Positive Mood | 0.15 Score on a scale | Standard Deviation 1.75 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 17.Cravings for starchy foods | -0.78 Score on a scale | Standard Deviation 3.04 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 7.Feeling of alertness | 0.07 Score on a scale | Standard Deviation 2.73 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 18.Cravings for savoury foods | -0.61 Score on a scale | Standard Deviation 3.02 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 2.Feeling of fullness | 0.35 Score on a scale | Standard Deviation 2.75 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 18.Cravings for savoury foods | -0.60 Score on a scale | Standard Deviation 2.92 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 8.Feeling of contentment | 0.08 Score on a scale | Standard Deviation 2.37 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 19.Difficulty to control eating general | -0.90 Score on a scale | Standard Deviation 3.09 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: Craving for Sweet | -0.25 Score on a scale | Standard Deviation 2.15 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 19.Difficulty to control eating general | -0.97 Score on a scale | Standard Deviation 3.01 |
| Oral Semaglutide 14 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: Craving control | 0.46 Score on a scale | Standard Deviation 2.6 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 19.Difficulty to control eating general | -0.27 Score on a scale | Standard Deviation 2.82 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: Craving control | 0.21 Score on a scale | Standard Deviation 2.26 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: Craving control | 0.18 Score on a scale | Standard Deviation 2.38 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: Positive Mood | 0.19 Score on a scale | Standard Deviation 1.62 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: Positive Mood | 0.17 Score on a scale | Standard Deviation 1.64 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: Craving for Savoury | -0.54 Score on a scale | Standard Deviation 2.05 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: Craving for Savoury | -0.44 Score on a scale | Standard Deviation 2.14 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: Craving for Sweet | -0.21 Score on a scale | Standard Deviation 2.04 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: Craving for Sweet | -0.17 Score on a scale | Standard Deviation 2.13 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 1.Feeling of hunger | -0.09 Score on a scale | Standard Deviation 2.59 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 1.Feeling of hunger | 0.07 Score on a scale | Standard Deviation 2.56 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 2.Feeling of fullness | 0.29 Score on a scale | Standard Deviation 2.63 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 2.Feeling of fullness | 0.06 Score on a scale | Standard Deviation 2.67 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 3.Desire to eat sweet foods | -0.22 Score on a scale | Standard Deviation 2.95 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 3.Desire to eat sweet foods | -0.18 Score on a scale | Standard Deviation 2.85 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 4.Desire to eat savoury foods | -0.56 Score on a scale | Standard Deviation 3.09 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 4.Desire to eat savoury foods | -0.57 Score on a scale | Standard Deviation 2.93 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 5.Feeling of happiness | 0.21 Score on a scale | Standard Deviation 2.31 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 5.Feeling of happiness | 0.21 Score on a scale | Standard Deviation 2.36 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 6.Feeling of anxiousness | -0.31 Score on a scale | Standard Deviation 3.22 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 6.Feeling of anxiousness | -0.21 Score on a scale | Standard Deviation 3.02 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 7.Feeling of alertness | 0.02 Score on a scale | Standard Deviation 2.57 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 7.Feeling of alertness | 0.08 Score on a scale | Standard Deviation 2.63 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 8.Feeling of contentment | 0.22 Score on a scale | Standard Deviation 2.42 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 8.Feeling of contentment | 0.17 Score on a scale | Standard Deviation 2.3 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 9.Food cravings during 7 days | -0.03 Score on a scale | Standard Deviation 3.03 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 9.Food cravings during 7 days | -0.17 Score on a scale | Standard Deviation 2.98 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 10.Strength of food cravings | -0.18 Score on a scale | Standard Deviation 2.97 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 10.Strength of food cravings | -0.14 Score on a scale | Standard Deviation 3.01 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 11.Difficulty to resist food cravings | -0.35 Score on a scale | Standard Deviation 3.18 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 11.Difficulty to resist food cravings | -0.30 Score on a scale | Standard Deviation 3.24 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 12.Eating in response to food cravings | -0.12 Score on a scale | Standard Deviation 2.75 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 12.Eating in response to food cravings | -0.01 Score on a scale | Standard Deviation 2.93 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 13.Cravings for chocolate | -0.26 Score on a scale | Standard Deviation 3.02 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 13.Cravings for chocolate | -0.12 Score on a scale | Standard Deviation 3 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 14.Cravings for other sweet foods | -0.36 Score on a scale | Standard Deviation 2.94 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 14.Cravings for other sweet foods | -0.24 Score on a scale | Standard Deviation 3.13 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 15.Cravings for fruit or fruit juice | 0.01 Score on a scale | Standard Deviation 3.11 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 15.Cravings for fruit or fruit juice | -0.15 Score on a scale | Standard Deviation 3.14 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 16.Cravings for dairy foods | -0.43 Score on a scale | Standard Deviation 2.88 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 16.Cravings for dairy foods | -0.16 Score on a scale | Standard Deviation 2.92 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 17.Cravings for starchy foods | -0.59 Score on a scale | Standard Deviation 2.64 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 17.Cravings for starchy foods | -0.51 Score on a scale | Standard Deviation 2.99 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 18.Cravings for savoury foods | -0.56 Score on a scale | Standard Deviation 2.93 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 52: 18.Cravings for savoury foods | -0.50 Score on a scale | Standard Deviation 3.09 |
| Empagliflozin 25 mg | Change in CoEQ: Scores From the 4 Domains and the 19 Items | Week 26: 19.Difficulty to control eating general | -0.36 Score on a scale | Standard Deviation 2.79 |
Secondary
Change in C-reactive Protein (Ratio to Baseline)
Change from baseline (week 0) in C-reactive protein (milligrams per liter \[mg/L\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in C-reactive Protein (Ratio to Baseline) | Week 26 | 0.69 Ratio of C-reactive protein | Geometric Coefficient of Variation 121.5 |
| Oral Semaglutide 14 mg | Change in C-reactive Protein (Ratio to Baseline) | Week 52 | 0.68 Ratio of C-reactive protein | Geometric Coefficient of Variation 129.7 |
| Empagliflozin 25 mg | Change in C-reactive Protein (Ratio to Baseline) | Week 26 | 0.98 Ratio of C-reactive protein | Geometric Coefficient of Variation 115.7 |
| Empagliflozin 25 mg | Change in C-reactive Protein (Ratio to Baseline) | Week 52 | 0.90 Ratio of C-reactive protein | Geometric Coefficient of Variation 126.3 |
Secondary
Change in ECG
Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at week 26 and week 52. Change from baseline results are presented as shift in findings (normal, abnormal and not clinically significant (NCS), and abnormal and clinically significant (CS)) from week 0 to week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26, week 52
Population: Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in ECG | Normal (week 0) to normal (week 26) | 207 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Normal (week 0) to abnormal NCS (week 26) | 30 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Normal (week 0) to abnormal CS (week 26) | 1 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal NCS (week 0) to normal (week 26) | 50 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal NCS (week 0) to abnormal NCS (week 26) | 97 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal NCS (week 0) to abnormal CS (week 26) | 0 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal CS (week 0) to normal (week 26) | 1 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal CS (week 0) CS to abnormal NCS (week 26) | 2 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal CS (week 0) to abnormal CS (week 26) | 1 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Normal (week 0) to normal (week 52) | 196 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Normal (week 0) to abnormal NCS (week 52) | 39 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Normal (week 0) to abnormal CS (week 52) | 0 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal (week 0) NCS to normal (week 52) | 46 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal (week 0) NCS to abnormal NCS (week 52) | 98 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal (week 0) NCS to abnormal CS (week 52) | 1 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal CS (week 0) to normal (week 52) | 1 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal CS (week 0) to abnormal NCS (week 52) | 2 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal CS (week 0) to abnormal CS (week 52) | 1 Participants |
| Empagliflozin 25 mg | Change in ECG | Abnormal (week 0) NCS to abnormal NCS (week 52) | 97 Participants |
| Empagliflozin 25 mg | Change in ECG | Normal (week 0) to normal (week 26) | 203 Participants |
| Empagliflozin 25 mg | Change in ECG | Normal (week 0) to normal (week 52) | 194 Participants |
| Empagliflozin 25 mg | Change in ECG | Normal (week 0) to abnormal NCS (week 26) | 37 Participants |
| Empagliflozin 25 mg | Change in ECG | Abnormal CS (week 0) to abnormal CS (week 52) | 1 Participants |
| Empagliflozin 25 mg | Change in ECG | Normal (week 0) to abnormal CS (week 26) | 2 Participants |
| Empagliflozin 25 mg | Change in ECG | Normal (week 0) to abnormal NCS (week 52) | 39 Participants |
| Empagliflozin 25 mg | Change in ECG | Abnormal NCS (week 0) to normal (week 26) | 41 Participants |
| Empagliflozin 25 mg | Change in ECG | Abnormal (week 0) NCS to abnormal CS (week 52) | 2 Participants |
| Empagliflozin 25 mg | Change in ECG | Abnormal NCS (week 0) to abnormal NCS (week 26) | 110 Participants |
| Empagliflozin 25 mg | Change in ECG | Normal (week 0) to abnormal CS (week 52) | 2 Participants |
| Empagliflozin 25 mg | Change in ECG | Abnormal NCS (week 0) to abnormal CS (week 26) | 0 Participants |
| Empagliflozin 25 mg | Change in ECG | Abnormal CS (week 0) to abnormal NCS (week 52) | 0 Participants |
| Empagliflozin 25 mg | Change in ECG | Abnormal CS (week 0) to normal (week 26) | 0 Participants |
| Empagliflozin 25 mg | Change in ECG | Abnormal (week 0) NCS to normal (week 52) | 45 Participants |
| Empagliflozin 25 mg | Change in ECG | Abnormal CS (week 0) CS to abnormal NCS (week 26) | 0 Participants |
| Empagliflozin 25 mg | Change in ECG | Abnormal CS (week 0) to normal (week 52) | 0 Participants |
| Empagliflozin 25 mg | Change in ECG | Abnormal CS (week 0) to abnormal CS (week 26) | 1 Participants |
Secondary
Change in Eye Examination
The eye examination findings (normal, abnormal NCS and abnormal CS) of the participants at baseline (week -2) and week 52 are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week -2, week 52
Population: Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Eye Examination | Left eye (week -2) | Abnormal NCS | 107 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Right eye (week 52) | Abnormal CS | 11 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Left eye (week -2) | Normal | 295 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Left eye (week -2) | Abnormal CS | 7 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Left eye (week 52) | Normal | 264 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Left eye (week 52) | Abnormal NCS | 103 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Left eye (week 52) | Abnormal CS | 8 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Right eye (week -2) | Normal | 294 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Right eye (week -2) | Abnormal NCS | 109 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Right eye (week -2) | Abnormal CS | 6 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Right eye (week 52) | Normal | 267 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Right eye (week 52) | Abnormal NCS | 96 Participants |
| Empagliflozin 25 mg | Change in Eye Examination | Right eye (week 52) | Normal | 269 Participants |
| Empagliflozin 25 mg | Change in Eye Examination | Left eye (week 52) | Abnormal CS | 10 Participants |
| Empagliflozin 25 mg | Change in Eye Examination | Right eye (week 52) | Abnormal CS | 11 Participants |
| Empagliflozin 25 mg | Change in Eye Examination | Right eye (week -2) | Abnormal CS | 9 Participants |
| Empagliflozin 25 mg | Change in Eye Examination | Left eye (week -2) | Normal | 295 Participants |
| Empagliflozin 25 mg | Change in Eye Examination | Left eye (week -2) | Abnormal NCS | 102 Participants |
| Empagliflozin 25 mg | Change in Eye Examination | Right eye (week -2) | Normal | 293 Participants |
| Empagliflozin 25 mg | Change in Eye Examination | Left eye (week -2) | Abnormal CS | 10 Participants |
| Empagliflozin 25 mg | Change in Eye Examination | Right eye (week 52) | Abnormal NCS | 93 Participants |
| Empagliflozin 25 mg | Change in Eye Examination | Left eye (week 52) | Normal | 269 Participants |
| Empagliflozin 25 mg | Change in Eye Examination | Right eye (week -2) | Abnormal NCS | 107 Participants |
| Empagliflozin 25 mg | Change in Eye Examination | Left eye (week 52) | Abnormal NCS | 93 Participants |
Secondary
Change in Fasting C-peptide (Ratio to Baseline)
Change from baseline (week 0) in fasting C-peptide (Nanomoles per liter \[nmol/L\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Fasting C-peptide (Ratio to Baseline) | week 26 | 1.10 Ratio of C-peptide | Geometric Coefficient of Variation 35.7 |
| Oral Semaglutide 14 mg | Change in Fasting C-peptide (Ratio to Baseline) | week 52 | 1.09 Ratio of C-peptide | Geometric Coefficient of Variation 37.2 |
| Empagliflozin 25 mg | Change in Fasting C-peptide (Ratio to Baseline) | week 26 | 0.89 Ratio of C-peptide | Geometric Coefficient of Variation 29.4 |
| Empagliflozin 25 mg | Change in Fasting C-peptide (Ratio to Baseline) | week 52 | 0.92 Ratio of C-peptide | Geometric Coefficient of Variation 31.6 |
Secondary
Change in Fasting Free Fatty Acids (Ratio to Baseline)
Change from baseline (week 0) in fasting free fatty acids (FFA) (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. Because of an issue with the handling of the blood samples for FFA, all FFA data are considered invalid for this trial; thus, no conclusion with regards to FFA levels can be made based on the FFA data. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Fasting Free Fatty Acids (Ratio to Baseline) | Week 26 | 0.95 Ratio of FFA | Geometric Coefficient of Variation 51.3 |
| Oral Semaglutide 14 mg | Change in Fasting Free Fatty Acids (Ratio to Baseline) | Week 52 | 0.88 Ratio of FFA | Geometric Coefficient of Variation 53 |
| Empagliflozin 25 mg | Change in Fasting Free Fatty Acids (Ratio to Baseline) | Week 26 | 1.05 Ratio of FFA | Geometric Coefficient of Variation 46.9 |
| Empagliflozin 25 mg | Change in Fasting Free Fatty Acids (Ratio to Baseline) | Week 52 | 0.97 Ratio of FFA | Geometric Coefficient of Variation 49.2 |
Secondary
Change in Fasting Glucagon (Ratio to Baseline)
Change from baseline (week 0) in fasting glucagon (picograms per milliliter \[pg/mL\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Fasting Glucagon (Ratio to Baseline) | Week 26 | 0.91 Ratio of glucagon | Geometric Coefficient of Variation 28 |
| Oral Semaglutide 14 mg | Change in Fasting Glucagon (Ratio to Baseline) | Week 52 | 0.89 Ratio of glucagon | Geometric Coefficient of Variation 27.8 |
| Empagliflozin 25 mg | Change in Fasting Glucagon (Ratio to Baseline) | Week 26 | 1.01 Ratio of glucagon | Geometric Coefficient of Variation 27.5 |
| Empagliflozin 25 mg | Change in Fasting Glucagon (Ratio to Baseline) | Week 52 | 0.95 Ratio of glucagon | Geometric Coefficient of Variation 27.6 |
Secondary
Change in Fasting HDL Cholesterol (Ratio to Baseline)
Change from baseline (week 0) in fasting high density lipoprotein (HDL) cholesterol (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Fasting HDL Cholesterol (Ratio to Baseline) | Week 26 | 1.01 Ratio of HDL cholesterol | Geometric Coefficient of Variation 13 |
| Oral Semaglutide 14 mg | Change in Fasting HDL Cholesterol (Ratio to Baseline) | Week 52 | 1.01 Ratio of HDL cholesterol | Geometric Coefficient of Variation 13.9 |
| Empagliflozin 25 mg | Change in Fasting HDL Cholesterol (Ratio to Baseline) | Week 26 | 1.07 Ratio of HDL cholesterol | Geometric Coefficient of Variation 15.9 |
| Empagliflozin 25 mg | Change in Fasting HDL Cholesterol (Ratio to Baseline) | Week 52 | 1.06 Ratio of HDL cholesterol | Geometric Coefficient of Variation 14 |
Secondary
Change in Fasting Insulin (Ratio to Baseline)
Change from baseline (week 0) in fasting insulin (picomoles per liter \[pmol/L\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Fasting Insulin (Ratio to Baseline) | Week 26 | 1.06 Ratio of insulin | Geometric Coefficient of Variation 50.5 |
| Oral Semaglutide 14 mg | Change in Fasting Insulin (Ratio to Baseline) | Week 52 | 1.03 Ratio of insulin | Geometric Coefficient of Variation 52.8 |
| Empagliflozin 25 mg | Change in Fasting Insulin (Ratio to Baseline) | Week 26 | 0.77 Ratio of insulin | Geometric Coefficient of Variation 54.1 |
| Empagliflozin 25 mg | Change in Fasting Insulin (Ratio to Baseline) | Week 52 | 0.77 Ratio of insulin | Geometric Coefficient of Variation 53.7 |
Secondary
Change in Fasting LDL Cholesterol (Ratio to Baseline)
Change from baseline (week 0) in fasting low density lipoprotein (LDL) cholesterol (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Fasting LDL Cholesterol (Ratio to Baseline) | Week 26 | 0.96 Ratio of LDL cholesterol | Geometric Coefficient of Variation 38.3 |
| Oral Semaglutide 14 mg | Change in Fasting LDL Cholesterol (Ratio to Baseline) | Week 52 | 0.97 Ratio of LDL cholesterol | Geometric Coefficient of Variation 30.1 |
| Empagliflozin 25 mg | Change in Fasting LDL Cholesterol (Ratio to Baseline) | Week 26 | 1.03 Ratio of LDL cholesterol | Geometric Coefficient of Variation 24.6 |
| Empagliflozin 25 mg | Change in Fasting LDL Cholesterol (Ratio to Baseline) | Week 52 | 1.03 Ratio of LDL cholesterol | Geometric Coefficient of Variation 27.2 |
Secondary
Change in Fasting Plasma Glucose
Change from baseline (week 0) in fasting plasma glucose was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26, week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Fasting Plasma Glucose | Week 26 | -2.01 Millimoles per liter (mmol/L) | Standard Deviation 2.56 |
| Oral Semaglutide 14 mg | Change in Fasting Plasma Glucose | Week 52 | -2.04 Millimoles per liter (mmol/L) | Standard Deviation 2.5 |
| Empagliflozin 25 mg | Change in Fasting Plasma Glucose | Week 26 | -2.08 Millimoles per liter (mmol/L) | Standard Deviation 2.17 |
| Empagliflozin 25 mg | Change in Fasting Plasma Glucose | Week 52 | -2.14 Millimoles per liter (mmol/L) | Standard Deviation 2.36 |
Secondary
Change in Fasting Pro-insulin (Ratio to Baseline)
Change from baseline (week 0) in fasting pro-insulin (pmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Fasting Pro-insulin (Ratio to Baseline) | Week 26 | 0.72 Ratio of pro-insulin | Geometric Coefficient of Variation 74.6 |
| Oral Semaglutide 14 mg | Change in Fasting Pro-insulin (Ratio to Baseline) | Week 52 | 0.74 Ratio of pro-insulin | Geometric Coefficient of Variation 80.5 |
| Empagliflozin 25 mg | Change in Fasting Pro-insulin (Ratio to Baseline) | Week 26 | 0.66 Ratio of pro-insulin | Geometric Coefficient of Variation 61.9 |
| Empagliflozin 25 mg | Change in Fasting Pro-insulin (Ratio to Baseline) | Week 52 | 0.69 Ratio of pro-insulin | Geometric Coefficient of Variation 57.8 |
Secondary
Change in Fasting Total Cholesterol (Ratio to Baseline)
Change from baseline (week 0) in fasting total cholesterol (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Fasting Total Cholesterol (Ratio to Baseline) | Week 26 | 0.96 Ratio of total cholesterol | Geometric Coefficient of Variation 18.1 |
| Oral Semaglutide 14 mg | Change in Fasting Total Cholesterol (Ratio to Baseline) | Week 52 | 0.97 Ratio of total cholesterol | Geometric Coefficient of Variation 18.1 |
| Empagliflozin 25 mg | Change in Fasting Total Cholesterol (Ratio to Baseline) | Week 26 | 1.02 Ratio of total cholesterol | Geometric Coefficient of Variation 15.2 |
| Empagliflozin 25 mg | Change in Fasting Total Cholesterol (Ratio to Baseline) | Week 52 | 1.01 Ratio of total cholesterol | Geometric Coefficient of Variation 17.1 |
Secondary
Change in Fasting Triglycerides (Ratio to Baseline)
Change from baseline (week 0) in fasting triglycerides (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Fasting Triglycerides (Ratio to Baseline) | Week 26 | 0.88 Ratio of triglycerides | Geometric Coefficient of Variation 40.5 |
| Oral Semaglutide 14 mg | Change in Fasting Triglycerides (Ratio to Baseline) | Week 52 | 0.89 Ratio of triglycerides | Geometric Coefficient of Variation 42.3 |
| Empagliflozin 25 mg | Change in Fasting Triglycerides (Ratio to Baseline) | Week 26 | 0.90 Ratio of triglycerides | Geometric Coefficient of Variation 36.1 |
| Empagliflozin 25 mg | Change in Fasting Triglycerides (Ratio to Baseline) | Week 52 | 0.90 Ratio of triglycerides | Geometric Coefficient of Variation 39.3 |
Secondary
Change in Fasting VLDL Cholesterol (Ratio to Baseline)
Change from baseline (week 0) in fasting very low density lipoprotein (VLDL) cholesterol (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Fasting VLDL Cholesterol (Ratio to Baseline) | Week 26 | 0.89 Ratio of VLDL cholesterol | Geometric Coefficient of Variation 39 |
| Oral Semaglutide 14 mg | Change in Fasting VLDL Cholesterol (Ratio to Baseline) | Week 52 | 0.89 Ratio of VLDL cholesterol | Geometric Coefficient of Variation 39.3 |
| Empagliflozin 25 mg | Change in Fasting VLDL Cholesterol (Ratio to Baseline) | Week 26 | 0.91 Ratio of VLDL cholesterol | Geometric Coefficient of Variation 34.7 |
| Empagliflozin 25 mg | Change in Fasting VLDL Cholesterol (Ratio to Baseline) | Week 52 | 0.90 Ratio of VLDL cholesterol | Geometric Coefficient of Variation 37.6 |
Secondary
Change in HbA1c (%)
Change from baseline (week 0) in HbA1c was evaluated at week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in HbA1c (%) | -1.3 Percentage of HbA1c | Standard Deviation 1.2 |
| Empagliflozin 25 mg | Change in HbA1c (%) | -0.9 Percentage of HbA1c | Standard Deviation 1 |
Secondary
Change in HOMA-B (Ratio to Baseline)
Change from baseline (week 0) in homeostatic model assessment index of beta-cell function (HOMA-B) (%) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in HOMA-B (Ratio to Baseline) | Week 26 | 1.67 Ratio of HOMA-B | Geometric Coefficient of Variation 69.5 |
| Oral Semaglutide 14 mg | Change in HOMA-B (Ratio to Baseline) | Week 52 | 1.66 Ratio of HOMA-B | Geometric Coefficient of Variation 72.9 |
| Empagliflozin 25 mg | Change in HOMA-B (Ratio to Baseline) | Week 26 | 1.16 Ratio of HOMA-B | Geometric Coefficient of Variation 65 |
| Empagliflozin 25 mg | Change in HOMA-B (Ratio to Baseline) | Week 52 | 1.17 Ratio of HOMA-B | Geometric Coefficient of Variation 69.9 |
Secondary
Change in HOMA-IR (Ratio to Baseline)
Change from baseline (week 0) in homeostatic model assessment index of insulin resistance (HOMA-IR) (%) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in HOMA-IR (Ratio to Baseline) | Week 26 | 0.83 Ratio of HOMA-IR | Geometric Coefficient of Variation 63.8 |
| Oral Semaglutide 14 mg | Change in HOMA-IR (Ratio to Baseline) | Week 52 | 0.81 Ratio of HOMA-IR | Geometric Coefficient of Variation 64.9 |
| Empagliflozin 25 mg | Change in HOMA-IR (Ratio to Baseline) | Week 26 | 0.61 Ratio of HOMA-IR | Geometric Coefficient of Variation 58.7 |
| Empagliflozin 25 mg | Change in HOMA-IR (Ratio to Baseline) | Week 52 | 0.60 Ratio of HOMA-IR | Geometric Coefficient of Variation 60.4 |
Secondary
Change in Lipase (Ratio to Baseline)
Change from baseline (week 0) in lipase (U/L) at week 26 and week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Week 0, week 26, week 52
Population: Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Lipase (Ratio to Baseline) | Week 26 | 1.37 Ratio of lipase | Geometric Coefficient of Variation 62 |
| Oral Semaglutide 14 mg | Change in Lipase (Ratio to Baseline) | Week 52 | 1.27 Ratio of lipase | Geometric Coefficient of Variation 63.6 |
| Empagliflozin 25 mg | Change in Lipase (Ratio to Baseline) | Week 26 | 1.10 Ratio of lipase | Geometric Coefficient of Variation 50.8 |
| Empagliflozin 25 mg | Change in Lipase (Ratio to Baseline) | Week 52 | 1.07 Ratio of lipase | Geometric Coefficient of Variation 47.2 |
Secondary
Change in Physical Examination
The physical examination findings (normal, abnormal NCS and abnormal CS) of the participants at week -2 and week 52 are presented for the following examinations: Cardiovascular system, Nervous system (central and peripheral); Gastrointestinal system, incl. mouth; General appearance; Head (ears, eyes, nose), throat, neck; Lymph node palpation; Musculoskeletal system; Respiratory system; Skin; Thyroid gland. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week -2, week 52
Population: Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Physical Examination | Head, throat, neck (week 52) | Normal | 376 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Head, throat, neck (week 52) | Abnormal NCS | 8 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Nervous system (week 52) | Abnormal CS | 1 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Head, throat, neck (week 52) | Abnormal CS | 1 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Gastrointestinal system (week -2) | Normal | 387 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Lymph node palpation (week -2) | Normal | 409 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Thyroid gland (week 52) | Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Lymph node palpation (week -2) | Abnormal NCS | 1 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Gastrointestinal system (week -2) | Abnormal NCS | 23 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Lymph node palpation (week -2) | Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Cardiovascular system (week 52) | Abnormal NCS | 21 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Lymph node palpation (week 52) | Normal | 385 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Gastrointestinal system (week -2) | Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Lymph node palpation (week 52) | Abnormal NCS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Lymph node palpation (week 52) | Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Cardiovascular system (week -2) | Normal | 381 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Musculoskeletal system (week -2) | Normal | 389 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Gastrointestinal system (week 52) | Normal | 366 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Musculoskeletal system (week -2) | Abnormal NCS | 18 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Cardiovascular system (week 52) | Abnormal CS | 4 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Musculoskeletal system (week -2) | Abnormal CS | 3 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Gastrointestinal system (week 52) | Abnormal NCS | 18 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Musculoskeletal system (week 52) | Normal | 370 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | General appearance (week -2) | Abnormal NCS | 47 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Musculoskeletal system (week 52) | Abnormal NCS | 15 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Gastrointestinal system (week 52) | Abnormal CS | 1 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Musculoskeletal system (week 52) | Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Nervous system (week -2) | Normal | 390 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Respiratory system (week -2) | Normal | 400 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | General appearance (week -2) | Normal | 354 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Respiratory system (week -2) | Abnormal CS | 1 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Cardiovascular system (week -2) | Abnormal NCS | 24 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Respiratory system (week 52) | Normal | 375 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Nervous system (week -2) | Abnormal NCS | 20 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Thyroid gland (week 52) | Abnormal NCS | 9 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | General appearance (week -2) | Abnormal CS | 9 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Respiratory system (week 52) | Abnormal NCS | 8 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Respiratory system (week -2) | Abnormal NCS | 9 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Respiratory system (week 52) | Abnormal CS | 2 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | General appearance (week 52) | Normal | 345 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Skin (week -2) | Normal | 357 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Nervous system (week -2) | Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Skin (week -2) | Abnormal NCS | 50 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | General appearance (week 52) | Abnormal NCS | 36 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Skin (week -2) | Abnormal CS | 3 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Cardiovascular system (week -2) | Abnormal CS | 5 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Skin (week 52) | Normal | 346 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | General appearance (week 52) | Abnormal CS | 4 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Skin (week 52) | Abnormal NCS | 37 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Nervous system (week 52) | Normal | 371 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Skin (week 52) | Abnormal CS | 2 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Head, throat, neck (week -2) | Normal | 389 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Thyroid gland (week -2) | Normal | 399 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Thyroid gland (week -2) | Abnormal NCS | 11 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Head, throat, neck (week -2) | Abnormal NCS | 18 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Thyroid gland (week -2) | Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Nervous system (week 52) | Abnormal NCS | 13 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Thyroid gland (week 52) | Normal | 376 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Head, throat, neck (week -2) | Abnormal CS | 3 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | Cardiovascular system (week 52) | Normal | 360 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Thyroid gland (week 52) | Abnormal CS | 0 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Head, throat, neck (week 52) | Normal | 362 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Lymph node palpation (week 52) | Abnormal NCS | 0 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Respiratory system (week -2) | Normal | 403 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Cardiovascular system (week -2) | Normal | 372 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Cardiovascular system (week -2) | Abnormal NCS | 34 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Cardiovascular system (week -2) | Abnormal CS | 3 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Cardiovascular system (week 52) | Normal | 351 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Cardiovascular system (week 52) | Abnormal NCS | 29 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Cardiovascular system (week 52) | Abnormal CS | 2 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Nervous system (week -2) | Normal | 376 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Nervous system (week -2) | Abnormal NCS | 30 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Nervous system (week -2) | Abnormal CS | 3 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Nervous system (week 52) | Normal | 365 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Nervous system (week 52) | Abnormal NCS | 17 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Gastrointestinal system (week -2) | Normal | 384 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Gastrointestinal system (week -2) | Abnormal NCS | 24 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Gastrointestinal system (week -2) | Abnormal CS | 1 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Gastrointestinal system (week 52) | Normal | 360 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Gastrointestinal system (week 52) | Abnormal NCS | 22 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Gastrointestinal system (week 52) | Abnormal CS | 0 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | General appearance (week -2) | Normal | 354 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | General appearance (week -2) | Abnormal NCS | 49 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | General appearance (week -2) | Abnormal CS | 6 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | General appearance (week 52) | Normal | 338 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | General appearance (week 52) | Abnormal NCS | 41 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | General appearance (week 52) | Abnormal CS | 4 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Head, throat, neck (week -2) | Normal | 382 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Head, throat, neck (week -2) | Abnormal NCS | 26 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Head, throat, neck (week -2) | Abnormal CS | 1 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Head, throat, neck (week 52) | Abnormal NCS | 19 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Head, throat, neck (week 52) | Abnormal CS | 2 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Lymph node palpation (week -2) | Normal | 409 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Lymph node palpation (week -2) | Abnormal NCS | 0 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Lymph node palpation (week -2) | Abnormal CS | 0 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Lymph node palpation (week 52) | Normal | 381 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Lymph node palpation (week 52) | Abnormal CS | 0 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Musculoskeletal system (week -2) | Normal | 384 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Musculoskeletal system (week -2) | Abnormal NCS | 25 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Musculoskeletal system (week -2) | Abnormal CS | 0 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Musculoskeletal system (week 52) | Normal | 363 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Musculoskeletal system (week 52) | Abnormal NCS | 20 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Musculoskeletal system (week 52) | Abnormal CS | 0 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Respiratory system (week -2) | Abnormal NCS | 6 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Respiratory system (week -2) | Abnormal CS | 0 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Thyroid gland (week 52) | Normal | 367 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Respiratory system (week 52) | Normal | 378 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Respiratory system (week 52) | Abnormal NCS | 4 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Respiratory system (week 52) | Abnormal CS | 0 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Skin (week -2) | Normal | 354 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Skin (week -2) | Abnormal NCS | 53 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Skin (week -2) | Abnormal CS | 2 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Skin (week 52) | Normal | 340 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Skin (week 52) | Abnormal NCS | 42 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Skin (week 52) | Abnormal CS | 1 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Thyroid gland (week -2) | Normal | 389 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Thyroid gland (week -2) | Abnormal NCS | 18 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Thyroid gland (week -2) | Abnormal CS | 2 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Thyroid gland (week 52) | Abnormal NCS | 16 Participants |
| Empagliflozin 25 mg | Change in Physical Examination | Nervous system (week 52) | Abnormal CS | 1 Participants |
Secondary
Change in Pulse Rate
Change from baseline (week 0) in pulse rate was evaluated at week 26 and week 52. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Week 0, week 26, week 52
Population: Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Pulse Rate | Week 26 | 1 Beats/minute | Standard Deviation 10 |
| Oral Semaglutide 14 mg | Change in Pulse Rate | Week 52 | 1 Beats/minute | Standard Deviation 10 |
| Empagliflozin 25 mg | Change in Pulse Rate | Week 26 | -2 Beats/minute | Standard Deviation 9 |
| Empagliflozin 25 mg | Change in Pulse Rate | Week 52 | -2 Beats/minute | Standard Deviation 9 |
Secondary
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS)
SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at weeks 26 and 52. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.
Time frame: Week 0, week 26, week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Physical Functioning | 0.57 Score on a scale | Standard Deviation 6.79 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Vitality | 0.83 Score on a scale | Standard Deviation 7.72 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Bodily pain | -0.32 Score on a scale | Standard Deviation 9.77 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Social functioning | 0.50 Score on a scale | Standard Deviation 7.28 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Physical Functioning | 0.87 Score on a scale | Standard Deviation 7.35 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Social functioning | -0.18 Score on a scale | Standard Deviation 8.35 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Bodily pain | -0.33 Score on a scale | Standard Deviation 10.07 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Role emotional | 0.67 Score on a scale | Standard Deviation 9.47 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Role functioning | 0.07 Score on a scale | Standard Deviation 6.82 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Role emotional | 0.30 Score on a scale | Standard Deviation 9.63 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: General health | 2.26 Score on a scale | Standard Deviation 6.59 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Mental health | 0.94 Score on a scale | Standard Deviation 8.06 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: MCS | 0.83 Score on a scale | Standard Deviation 7.54 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Mental health | 0.29 Score on a scale | Standard Deviation 8.71 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: General health | 2.47 Score on a scale | Standard Deviation 7.35 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: PCS | 0.53 Score on a scale | Standard Deviation 6.36 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Role functioning | -0.61 Score on a scale | Standard Deviation 6.78 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: PCS | 0.44 Score on a scale | Standard Deviation 6.26 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: MCS | 0.35 Score on a scale | Standard Deviation 8.36 |
| Oral Semaglutide 14 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Vitality | 0.66 Score on a scale | Standard Deviation 7.58 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: MCS | -0.09 Score on a scale | Standard Deviation 8.64 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: MCS | -0.23 Score on a scale | Standard Deviation 8.4 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Physical Functioning | 0.99 Score on a scale | Standard Deviation 7.11 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Physical Functioning | 0.84 Score on a scale | Standard Deviation 7.32 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Role functioning | 0.56 Score on a scale | Standard Deviation 8.36 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Role functioning | 0.52 Score on a scale | Standard Deviation 7.93 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Bodily pain | 1.04 Score on a scale | Standard Deviation 9.53 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Bodily pain | 1.20 Score on a scale | Standard Deviation 9.54 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: General health | 1.36 Score on a scale | Standard Deviation 6.56 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: General health | 1.86 Score on a scale | Standard Deviation 7.66 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Vitality | 0.49 Score on a scale | Standard Deviation 7.6 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Vitality | 1.15 Score on a scale | Standard Deviation 7.48 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Social functioning | -0.54 Score on a scale | Standard Deviation 8.15 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Social functioning | -0.54 Score on a scale | Standard Deviation 8.63 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Role emotional | 0.53 Score on a scale | Standard Deviation 9.49 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Role emotional | 0.42 Score on a scale | Standard Deviation 9.93 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: Mental health | -0.03 Score on a scale | Standard Deviation 8.7 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: Mental health | -0.03 Score on a scale | Standard Deviation 9.21 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 26: PCS | 1.21 Score on a scale | Standard Deviation 6.39 |
| Empagliflozin 25 mg | Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) | Week 52: PCS | 1.36 Score on a scale | Standard Deviation 6.5 |
Secondary
Change in SMPG : Mean of the 7-point Profile
Change from baseline (week 0) in mean of the 7-point self-measured plasma glucose (SMPG) (i.e. before and after breakfast, lunch and dinner, and at bedtime) profile was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in SMPG : Mean of the 7-point Profile | Week 26 | -2.3 mmol/L | Standard Deviation 2.1 |
| Oral Semaglutide 14 mg | Change in SMPG : Mean of the 7-point Profile | Week 52 | -2.3 mmol/L | Standard Deviation 2.3 |
| Empagliflozin 25 mg | Change in SMPG : Mean of the 7-point Profile | Week 26 | -1.9 mmol/L | Standard Deviation 2.1 |
| Empagliflozin 25 mg | Change in SMPG : Mean of the 7-point Profile | Week 52 | -2.1 mmol/L | Standard Deviation 2.3 |
Secondary
Change in SMPG : Mean Postprandial Increment Over All Meals
Change from baseline (week 0) in mean postprandial glucose increment was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in SMPG : Mean Postprandial Increment Over All Meals | Week 26 | -0.5 mmol/L | Standard Deviation 1.8 |
| Oral Semaglutide 14 mg | Change in SMPG : Mean Postprandial Increment Over All Meals | Week 52 | -0.6 mmol/L | Standard Deviation 1.8 |
| Empagliflozin 25 mg | Change in SMPG : Mean Postprandial Increment Over All Meals | Week 26 | -0.4 mmol/L | Standard Deviation 2 |
| Empagliflozin 25 mg | Change in SMPG : Mean Postprandial Increment Over All Meals | Week 52 | -0.4 mmol/L | Standard Deviation 1.9 |
Secondary
Change in Waist Circumference
Change from baseline (week 0) in waist circumference was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 0, week 26, week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Waist Circumference | Week 26 | -3.9 Centimetre (cm) | Standard Deviation 5.1 |
| Oral Semaglutide 14 mg | Change in Waist Circumference | Week 52 | -3.7 Centimetre (cm) | Standard Deviation 5.5 |
| Empagliflozin 25 mg | Change in Waist Circumference | Week 26 | -2.9 Centimetre (cm) | Standard Deviation 5 |
| Empagliflozin 25 mg | Change in Waist Circumference | Week 52 | -2.9 Centimetre (cm) | Standard Deviation 5.8 |
Secondary
Number of Treatment-emergent Adverse Events (TEAE)
A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) with onset in the on-treatment observation period (the time period where participants are considered treated with trial product) and was assessed up to approximately 57 weeks (52-week treatment period plus the 5-week follow-up period).
Time frame: Weeks 0-57
Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants who received at least one dose of trial product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Semaglutide 14 mg | Number of Treatment-emergent Adverse Events (TEAE) | 1022 Events |
| Empagliflozin 25 mg | Number of Treatment-emergent Adverse Events (TEAE) | 948 Events |
Secondary
Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes
Treatment-emergent hypoglycaemia is an episode with onset in the on-treatment observation period (the time period where participants are considered treated with trial product) and was assessed up to approximately 57 weeks (52-week treatment period plus the 5-week follow-up period). Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Weeks 0-57
Population: Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Semaglutide 14 mg | Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes | 10 Episodes |
| Empagliflozin 25 mg | Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes | 9 Episodes |
Secondary
Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no)
This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide binding antibodies cross reacting with native glucagon-like peptide-1 (GLP-1) anytime during post-baseline visits (week 0 to week 57) are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Weeks 0-57
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Semaglutide 14 mg | Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no) | 0 Participants |
Secondary
Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)
This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide binding antibodies anytime during post-baseline visits (week 0 to week 57) are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Weeks 0-57
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Semaglutide 14 mg | Occurrence of Anti-semaglutide Binding Antibodies (Yes/no) | 2 Participants |
Secondary
Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no)
This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide neutralising antibodies cross reacting with native GLP-1 anytime during post-baseline visits (week 0 to week 57) are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Weeks 0-57
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Semaglutide 14 mg | Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no) | 0 Participants |
Secondary
Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)
This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide neutralising antibodies anytime during post-baseline visits (week 0 to week 57) are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Weeks 0-57
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Semaglutide 14 mg | Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no) | 0 Participants |
Secondary
Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no)
Participants who achieved HbA1c ≤6.5% (48 mmol/mol) (American Association of Clinical Endocrinologists (AACE) target) at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | Week 26 | Yes | 186 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | Week 26 | No | 206 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | Week 52 | Yes | 182 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | Week 52 | No | 202 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | Week 52 | No | 299 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | Week 26 | Yes | 68 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | Week 52 | Yes | 83 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | Week 26 | No | 327 Participants |
Secondary
Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no)
Participants who achieved HbA1c \<7.0% (53 mmol/mol) (American Diabetes Association (ADA) target) at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) | Week 26 | Yes | 262 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) | Week 26 | No | 130 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) | Week 52 | Yes | 254 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) | Week 52 | No | 130 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) | Week 52 | No | 217 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) | Week 26 | Yes | 158 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) | Week 52 | Yes | 165 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) | Week 26 | No | 237 Participants |
Secondary
Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)
Participants who achieved HbA1c \<7.0% (53 mmol/mol) without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain at week 26 and week 52. Severe or BG-confirmed symptomatic hypoglycaemia: an episode, that is severe according to the ADA classification or BG-confirmed by a plasma glucose value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) | Week 26 | Yes | 237 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) | Week 26 | No | 155 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) | Week 52 | Yes | 214 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) | Week 52 | No | 170 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) | Week 52 | No | 233 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) | Week 26 | Yes | 141 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) | Week 52 | Yes | 149 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) | Week 26 | No | 254 Participants |
Secondary
Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)
Participants who achieved HbA1c reduction ≥1%-point and weight loss of ≥3% at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | week 26 | Yes | 177 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | week 26 | No | 215 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | week 52 | Yes | 164 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | week 52 | No | 220 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | week 52 | No | 281 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | week 26 | Yes | 111 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | week 52 | Yes | 101 Participants |
| Empagliflozin 25 mg | Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | week 26 | No | 284 Participants |
Secondary
Participants Who Achieve Weight Loss ≥10% (Yes/no)
Participants who achieved weight loss of ≥10% at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Participants Who Achieve Weight Loss ≥10% (Yes/no) | Week 26 | Yes | 49 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve Weight Loss ≥10% (Yes/no) | Week 26 | No | 344 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve Weight Loss ≥10% (Yes/no) | Week 52 | Yes | 58 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve Weight Loss ≥10% (Yes/no) | Week 52 | No | 328 Participants |
| Empagliflozin 25 mg | Participants Who Achieve Weight Loss ≥10% (Yes/no) | Week 52 | No | 353 Participants |
| Empagliflozin 25 mg | Participants Who Achieve Weight Loss ≥10% (Yes/no) | Week 26 | Yes | 27 Participants |
| Empagliflozin 25 mg | Participants Who Achieve Weight Loss ≥10% (Yes/no) | Week 52 | Yes | 30 Participants |
| Empagliflozin 25 mg | Participants Who Achieve Weight Loss ≥10% (Yes/no) | Week 26 | No | 369 Participants |
Secondary
Participants Who Achieve Weight Loss ≥5% (Yes/no)
Participants who achieved weight loss of ≥5% at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Week 26 and week 52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Participants Who Achieve Weight Loss ≥5% (Yes/no) | Week 26 | Yes | 162 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve Weight Loss ≥5% (Yes/no) | Week 26 | No | 231 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve Weight Loss ≥5% (Yes/no) | Week 52 | Yes | 156 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve Weight Loss ≥5% (Yes/no) | Week 52 | No | 230 Participants |
| Empagliflozin 25 mg | Participants Who Achieve Weight Loss ≥5% (Yes/no) | Week 52 | No | 233 Participants |
| Empagliflozin 25 mg | Participants Who Achieve Weight Loss ≥5% (Yes/no) | Week 26 | Yes | 143 Participants |
| Empagliflozin 25 mg | Participants Who Achieve Weight Loss ≥5% (Yes/no) | Week 52 | Yes | 150 Participants |
| Empagliflozin 25 mg | Participants Who Achieve Weight Loss ≥5% (Yes/no) | Week 26 | No | 253 Participants |
Secondary
Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)
Number of participants with treatment-emergent severe or BG-confirmed symptomatic hypoglycaemic episodes was recorded during week 0-57. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Weeks 0-57
Population: Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Semaglutide 14 mg | Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no) | 7 Participants |
| Empagliflozin 25 mg | Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no) | 8 Participants |
Secondary
Semaglutide Plasma Concentrations for Population PK Analyses
Semaglutide plasma concentrations were measured after 25 minutes post-dose at week 4, 26 and 52. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Weeks 0-52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Semaglutide Plasma Concentrations for Population PK Analyses | Week 4 | 3.5 Nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 84.5 |
| Oral Semaglutide 14 mg | Semaglutide Plasma Concentrations for Population PK Analyses | Week 26 | 15.6 Nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 112.4 |
| Oral Semaglutide 14 mg | Semaglutide Plasma Concentrations for Population PK Analyses | Week 52 | 14.4 Nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 136.6 |
Secondary
SNAC Plasma Concentrations
This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Sodium N-\[8-(2-hydroxybenzoyl) amino\]caprylate (SNAC) plasma concentrations were measured after 25 and 40 minutes post-dose at week 4, 26 and 52. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Weeks 0-52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | SNAC Plasma Concentrations | Week 52: 40 minutes post-dose | 301 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 290.2 |
| Oral Semaglutide 14 mg | SNAC Plasma Concentrations | Week 4: 25 minutes post-dose | 559 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 224.6 |
| Oral Semaglutide 14 mg | SNAC Plasma Concentrations | Week 4: 40 minutes post-dose | 375 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 210.4 |
| Oral Semaglutide 14 mg | SNAC Plasma Concentrations | Week 26: 25 minutes post-dose | 474 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 272.7 |
| Oral Semaglutide 14 mg | SNAC Plasma Concentrations | Week 26: 40 minutes post-dose | 373 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 200.6 |
| Oral Semaglutide 14 mg | SNAC Plasma Concentrations | Week 52: 25 minutes post-dose | 448 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 377.5 |
Secondary
Time to Additional Anti-diabetic Medication
Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Additional anti-diabetic medication: use of new anti-diabetic medication for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 26/week 52), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Time frame: Weeks 0-52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Semaglutide 14 mg | Time to Additional Anti-diabetic Medication | Week 0-26 | 17 Participants |
| Oral Semaglutide 14 mg | Time to Additional Anti-diabetic Medication | Week 0-52 | 52 Participants |
| Empagliflozin 25 mg | Time to Additional Anti-diabetic Medication | Week 0-26 | 13 Participants |
| Empagliflozin 25 mg | Time to Additional Anti-diabetic Medication | Week 0-52 | 56 Participants |
Comparison: Time to initiation of additional anti-diabetic medication was analysed using a Cox proportional hazards model with treatment and region as categorical fixed effects and baseline HbA1c as covariate. Withdrawal for any reason or lost to follow-up contributed to the analysis as events (initiation of additional anti-diabetic medication). Censoring time was one day before planned end of treatment.p-value: 0.355295% CI: [0.6, 1.2]Regression, Cox
Secondary
Time to Rescue Medication
Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Rescue medication: use of new antidiabetic medication as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 0) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period: the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Time frame: Weeks 0-52
Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Semaglutide 14 mg | Time to Rescue Medication | Week 0-26 | 8 Participants |
| Oral Semaglutide 14 mg | Time to Rescue Medication | Week 0-52 | 31 Participants |
| Empagliflozin 25 mg | Time to Rescue Medication | Week 0-26 | 5 Participants |
| Empagliflozin 25 mg | Time to Rescue Medication | Week 0-52 | 44 Participants |
Comparison: Time to initiation of rescue medication was analysed using a Cox proportional hazards model with treatment and region as categorical fixed effects and baseline HbA1c as covariate. Censoring time was one day before last day on trial product.p-value: 0.22595% CI: [0.47, 1.19]Cox proportional hazards model