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 placebo in subjects with type 2 diabetes and moderate renal impairment.
Interventions
DRUGsemaglutide
Oral administration once daily.
DRUGplacebo
Oral administration once daily.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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 for at least 90 days prior to day of screening * HbA1c (glycosylated haemoglobin) of 7.0-9.5% (53-80 mmol/mol) (both inclusive) * Moderate renal impairment defined as estimated glomerular filtration rate of 30-59 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration formula * Stable daily dose(s) within 90 days prior to the day of screening of any of the following treatment regimens: * 1-2 of the following oral anti-diabetic drugs: * Metformin equal or above 1500 mg or maximum tolerated dose documented in the subject medical record), * Sulfonylurea (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record) * Basal insulin alone (20% change in total daily dose of insulin glargine, insulin detemir, insulin degludec or NPH insulin) or * Metformin (equal or above 1500 mg or maximum tolerated dose documented in the subject medical record) in combination with basal insulin (20% change in total daily dose of insulin glargine, insulin detemir, insulin degludec or NPH insulin)
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 and randomisation * 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 alanine aminotransferase above 2.5 x upper normal limit * Rapidly progressing renal disease (e.g. such as acute glomerulonephritis) as judged by the investigator or known nephrotic albuminuria (above 2200 mg/24 hours or above 2200 mg/g) * Use of systemic immunosuppressive treatment within 90 days prior to screening * 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 * Known hypoglycaemic unawareness and/or recurrent severe hypoglycaemic episodes as judged by the investigator * 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)
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 the 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 and/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 and/or premature trial product discontinuation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 the 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 and/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 and/or premature trial product discontinuation. |
| Change in FPG | Week 0, week 26 | Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product. |
| Change in Body Weight (%) | Week 0, week 26 | Relative change from baseline (week 0) in body weight (kg) was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product. |
| Change in BMI | Week 0, week 26 | Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product. |
| Change in Waist Circumference | Week 0, week 26 | Change from baseline (week 0) in waist circumference was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product. |
| Participants Who Achieve HbA1c <7.0% (53 mmol/Mol), ADA Target (Yes/no) | Week 26 | Participants who achieved HbA1c \<7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product. |
| Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | Week 26 | Participants who achieved HbA1c ≤6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no), was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product. |
| Participants Who Achieve Weight Loss ≥5% (Yes/no) | Week 26 | Participants who achieved weight loss ≥5% of their baseline body weight (yes/no) was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product. |
| Participants Who Achieve Weight Loss ≥10% (Yes/no) | Week 26 | Participants who achieved weight loss of ≥10% of their baseline body weight (yes/no) was evaluated at week 26. Results are based on the 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 and/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 | Participants who achieved HbA1c \<7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) was evaluated at week 26. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the 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 and/or premature discontinuation of trial product. |
| Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | Week 26 | Participants who achieved HbA1c reduction ≥1% and weight loss of ≥3% (yes/no) was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product. |
| Change in Total Cholesterol (Ratio to Baseline) | Week 0, week 26 | Change from baseline (week 0) in total cholesterol (mmol/L) at week 26 is presented as ratio to baseline. Results are based on the 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 and/or premature discontinuation of trial product. |
| Change in LDL Cholesterol (Ratio to Baseline) | Week 0, week 26 | Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at week 26 is presented as ratio to baseline. Results are based on the 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 and/or premature discontinuation of trial product. |
| Change in HDL Cholesterol (Ratio to Baseline) | Week 0, week 26 | Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at week 26 is presented as ratio to baseline. Results are based on the 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 and/or premature discontinuation of trial product. |
| Change in CRP (Ratio to Baseline) | Week 0, week 26 | Change from baseline (week 0) in C-reactive protein (CRP) (mg/L) at week 26 is presented as ratio to baseline. Results are based on the 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 and/or premature discontinuation of trial product. |
| Time to Additional Anti-diabetic Medication | Weeks 0-26 | Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the period, from week 0 to week 26. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 26), 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. Results are based on the 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 and/or premature discontinuation of trial product. |
| Time to Rescue Medication | Weeks 0-26 | Presented results are the number of participants who had taken rescue medication anytime during the period, from week 0 to week 26. Rescue medication was defined as any new anti-diabetic medication used 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, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation. |
| Number of TEAEs | Weeks 0-31 | Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
| Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-31 | Treatment emergent severe or BG-confirmed symptomatic hypoglycaemic episodes were recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the first dose of trial product until last dose of trial product were considered treatment -emergent. Severe or BG-confirmed symptomatic hypoglycaemia was defined as 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. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
| Change in Triglycerides (Ratio to Baseline) | Week 0, week 26 | Change from baseline (week 0) in triglycerides (mmol/L) at week 26 is presented as ratio to baseline. Results are based on the 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 and/or premature discontinuation of trial product. |
| Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no) | Weeks 0-31 | Number of participants with treatment emergent severe or BG-confirmed symptomatic hypoglycaemic episodes was recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the first dose of trial product until last dose of trial product were considered treatment -emergent. Severe or BG-confirmed symptomatic hypoglycaemia was defined as 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. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
| Change in Amylase (Ratio to Baseline) | Week 0, week 26 | Change from baseline (week 0) in amylase (units/litre (U/L)) at week 26 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was 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 | Change from baseline (week 0) in lipase (U/L) at week 26 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was 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 | Change from baseline (week 0) in pulse rate was evaluated at week 26. Results are based on the data from the on-treatment observation period which was 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 | Change from baseline (week 0) in systolic and diastolic blood pressure was evaluated at week 26. Results are based on the data from the on-treatment observation period which was 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 | Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at week 26. 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. Results are based on the 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 and/or premature discontinuation of trial product. |
| Change in Physical Examination | Week -2, week 26 | Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (week \[wk\] -2) and wk 26 are presented. Results are based on the 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 and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system; 2) Nervous system (central and peripheral); 3) Gastrointestinal system, incl. mouth; 4) General appearance; 5) Head (ears, eyes, nose), throat, neck; 6) Lymph node palpation; 7) Musculoskeletal system; 8) Respiratory system; 9) Skin; 10) Thyroid gland. |
| Change in Eye Examination | Week -2, week 26 | Participants with eye examination findings, normal, abnormal NCS and abnormal CS at baseline (week -2) and week 26 are presented. Results are based on the 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 and/or premature discontinuation of trial product. |
| Occurrence of Anti-semaglutide Binding Antibodies (Yes/no) | Weeks 0-31 | 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 (weeks 0-31) are presented. Results are based on the 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 and/or premature discontinuation of trial product. |
| Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no) | Weeks 0-31 | 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 (weeks 0-31) are presented. Results are based on the 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 and/or premature discontinuation of trial product. |
| Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no) | Weeks 0-31 | 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 (weeks 0-31) are presented. Results are based on the 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 and/or premature discontinuation of trial product. |
| Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no) | Weeks 0-31 | 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 (weeks 0-31) are presented. Results are based on the 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 and/or premature discontinuation of trial product. |
| Anti-semaglutide Binding Antibody Levels | Weeks 0-31 | 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 (weeks 0-31). Results are presented as percentage of bound radioactivity-labelled semaglutide /total added radioactivity-labelled semaglutide (%B/T). Results are based on the 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 and/or premature discontinuation of trial product. |
| Semaglutide Plasma Concentrations for Population PK Analyses | Weeks 0-26 | This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Semaglutide plasma concentrations were measured at weeks 4, 8, 14 and 26. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
| SNAC Plasma Concentrations | Weeks 0-26 | 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 weeks 4, 14 and 26. Results are based on the data from the on-treatment observation period which was 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 | 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 week 26. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period. |
| Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | Week 0, week 26 | Change from baseline (week 0) in Diabetes Treatment Satisfaction Questionnaire - status version (DTSQs) was evaluated at week 26. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of hyperglycaemia and hypoglycaemia, respectively. Thus, lower scores indicate a perception of blood glucose levels being none of the time unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score has a minimum of 0 and a maximum of 36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. |
| Change in Urinalysis | Week -2, week 26 | Participants with urinalysis, leukocytes and erythrocytes findings, negative, trace, small, moderate or large at baseline (week \[wk\] 0) and wk 26 are presented. Participants with urinalysis, nitrit findings, negative or positive at baseline (wk 0) and wk 26 are presented. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
| Change in Urinary Albumin to Creatinine Ratio (Ratio to Baseline) | Week 0, week 26 | Change from baseline (week 0) in urinary albumin to creatinine ratio (mg/mmol) at week 26 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. |
Countries
Denmark, Finland, Israel, Poland, Russia, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The trial was conducted in 8 countries (107 sites screened/88 randomised subjects), as follows: Denmark: 7/4; Finland: 7/7; Israel: 7/6; Poland: 2/2; Russian Federation: 19/18; Sweden: 6/4; United Kingdom: 9/7; United States (US):50/40. In addition, 10 sites in the US were approved by the institutional review board, but didn't randomise any subject
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 were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26. | 163 |
| Placebo Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26. | 161 |
| Total | 324 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 2 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Oral Semaglutide 14 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 71 Years STANDARD_DEVIATION 8 | 70 Years STANDARD_DEVIATION 8 | 70 Years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 14 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 156 Participants | 147 Participants | 303 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Glycosylated haemoglobin (HbA1c) | 8.0 Percentage of HbA1c STANDARD_DEVIATION 0.7 | 7.9 Percentage of HbA1c STANDARD_DEVIATION 0.7 | 8.0 Percentage of HbA1c STANDARD_DEVIATION 0.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 9 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 158 Participants | 152 Participants | 310 Participants |
| Sex: Female, Male Female | 80 Participants | 88 Participants | 168 Participants |
| Sex: Female, Male Male | 83 Participants | 73 Participants | 156 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 163 | 2 / 161 |
| other Total, other adverse events | 75 / 163 | 32 / 161 |
| serious Total, serious adverse events | 17 / 163 | 17 / 161 |
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 the 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 and/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 and/or premature trial product discontinuation.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in HbA1c | In-trial | -1.1 Percentage of HbA1c | Standard Deviation 1 |
| Oral Semaglutide 14 mg | Change in HbA1c | On-treatment without rescue medication | -1.2 Percentage of HbA1c | Standard Deviation 0.9 |
| Placebo | Change in HbA1c | In-trial | -0.2 Percentage of HbA1c | Standard Deviation 0.9 |
| Placebo | Change in HbA1c | On-treatment without rescue medication | -0.1 Percentage 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, strata, 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: [-1, -0.6]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, strata, interaction strata and region as categorical fixed effects and the baseline value as covariate, all nested within visit, and an unstructured residual covariance matrix.p-value: <0.000195% CI: [-1.2, -0.8]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 (weeks 0-31). Results are presented as percentage of bound radioactivity-labelled semaglutide /total added radioactivity-labelled semaglutide (%B/T). Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Weeks 0-31
Population: Overall number of participants analysed = participants who were found positive for anti-semaglutide antibodies. As only one subject was analyzed, standard deviation could not be calculated.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Oral Semaglutide 14 mg | Anti-semaglutide Binding Antibody Levels | Week 4 | 3.1 %B/T |
| Oral Semaglutide 14 mg | Anti-semaglutide Binding Antibody Levels | Week 31 | 2.2 %B/T |
Secondary
Change in Amylase (Ratio to Baseline)
Change from baseline (week 0) in amylase (units/litre (U/L)) at week 26 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was 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
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Amylase (Ratio to Baseline) | 1.09 Ratio of amylase | Geometric Coefficient of Variation 22.9 |
| Placebo | Change in Amylase (Ratio to Baseline) | 0.99 Ratio of amylase | Geometric Coefficient of Variation 25.6 |
Secondary
Change in Blood Pressure (Systolic and Diastolic Blood Pressure)
Change from baseline (week 0) in systolic and diastolic blood pressure was evaluated at week 26. Results are based on the data from the on-treatment observation period which was 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
Population: Overall number of participants 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) | Systolic blood pressure | -8 mmHg | Standard Deviation 14 |
| Oral Semaglutide 14 mg | Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | Diastolic blood pressure | -3 mmHg | Standard Deviation 9 |
| Placebo | Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | Systolic blood pressure | 0 mmHg | Standard Deviation 13 |
| Placebo | Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | Diastolic blood pressure | 0 mmHg | Standard Deviation 8 |
Secondary
Change in BMI
Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in BMI | -1.2 kg/m^2 | Standard Deviation 1.3 |
| Placebo | Change in BMI | -0.3 kg/m^2 | Standard Deviation 1 |
Secondary
Change in Body Weight (%)
Relative change from baseline (week 0) in body weight (kg) was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 0, week 26
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 (%) | -3.75 Percentage change | Standard Deviation 4.1 |
| Placebo | Change in Body Weight (%) | -0.92 Percentage change | Standard Deviation 3.13 |
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 the 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 and/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 and/or premature trial product discontinuation.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = FAS which comprised all randomised participants. 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 | -3.5 kg | Standard Deviation 3.8 |
| Oral Semaglutide 14 mg | Change in Body Weight (kg) | On-treatment without rescue medication | -3.9 kg | Standard Deviation 3.6 |
| Placebo | Change in Body Weight (kg) | In-trial | -0.9 kg | Standard Deviation 2.9 |
| Placebo | Change in Body Weight (kg) | On-treatment without rescue medication | -0.9 kg | Standard Deviation 2.9 |
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 ANCOVA model with treatment, strata, 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: <0.000195% CI: [-3.2, -1.8]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, strata, interaction strata and region as categorical fixed effects and the baseline value as covariate, all nested within visit, and an unstructured residual covariance matrix.p-value: <0.000195% CI: [-3.5, -1.9]MMRM
Secondary
Change in CRP (Ratio to Baseline)
Change from baseline (week 0) in C-reactive protein (CRP) (mg/L) at week 26 is presented as ratio to baseline. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in CRP (Ratio to Baseline) | 0.86 Ratio of CRP | Geometric Coefficient of Variation 135.1 |
| Placebo | Change in CRP (Ratio to Baseline) | 1.00 Ratio of CRP | Geometric Coefficient of Variation 136 |
Secondary
Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed)
Change from baseline (week 0) in Diabetes Treatment Satisfaction Questionnaire - status version (DTSQs) was evaluated at week 26. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of hyperglycaemia and hypoglycaemia, respectively. Thus, lower scores indicate a perception of blood glucose levels being none of the time unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score has a minimum of 0 and a maximum of 36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 2) Feeling of unacceptably high blood sugars | -1.26 Score | Standard Deviation 2.17 |
| Oral Semaglutide 14 mg | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 6) Satisfaction with understanding of diabetes | 0.31 Score | Standard Deviation 1.42 |
| Oral Semaglutide 14 mg | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 3) Feeling of unacceptably low blood sugars | 0.11 Score | Standard Deviation 1.84 |
| Oral Semaglutide 14 mg | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 7) Recommending treatment to others | 0.71 Score | Standard Deviation 1.73 |
| Oral Semaglutide 14 mg | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 4) Convenience of treatment | 0.43 Score | Standard Deviation 1.41 |
| Oral Semaglutide 14 mg | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 8) Satisfaction to continue with present treatment | 0.58 Score | Standard Deviation 1.84 |
| Oral Semaglutide 14 mg | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 5) Flexibility of treatment | 0.37 Score | Standard Deviation 1.45 |
| Oral Semaglutide 14 mg | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | Total treatment satisfaction | 2.82 Score | Standard Deviation 6.61 |
| Oral Semaglutide 14 mg | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 1) Satisfaction with treatment | 0.41 Score | Standard Deviation 1.56 |
| Placebo | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | Total treatment satisfaction | 3.13 Score | Standard Deviation 7.25 |
| Placebo | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 1) Satisfaction with treatment | 0.74 Score | Standard Deviation 1.57 |
| Placebo | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 2) Feeling of unacceptably high blood sugars | -0.30 Score | Standard Deviation 2.08 |
| Placebo | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 3) Feeling of unacceptably low blood sugars | -0.32 Score | Standard Deviation 1.82 |
| Placebo | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 4) Convenience of treatment | 0.42 Score | Standard Deviation 1.76 |
| Placebo | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 5) Flexibility of treatment | 0.52 Score | Standard Deviation 1.45 |
| Placebo | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 6) Satisfaction with understanding of diabetes | 0.60 Score | Standard Deviation 1.59 |
| Placebo | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 7) Recommending treatment to others | 0.37 Score | Standard Deviation 1.61 |
| Placebo | Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) | 8) Satisfaction to continue with present treatment | 0.47 Score | Standard Deviation 1.87 |
Secondary
Change in ECG
Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at week 26. 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. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 0, week 26
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 | Abnormal (week 0) CS to abnormal CS (week 26) | 4 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Normal (week 0) to normal (week 26) | 38 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Normal (week 0) to abnormal NCS (week 26) | 13 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 (week 0) NCS to normal (week 26) | 12 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal (week 0) NCS to abnormal NCS (week 26) | 84 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal (week 0) NCS to abnormal CS (week 26) | 1 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal (week 0) CS to normal (week 26) | 0 Participants |
| Oral Semaglutide 14 mg | Change in ECG | Abnormal (week 0) CS to abnormal NCS (week 26) | 1 Participants |
| Placebo | Change in ECG | Abnormal (week 0) CS to normal (week 26) | 0 Participants |
| Placebo | Change in ECG | Abnormal (week 0) CS to abnormal CS (week 26) | 2 Participants |
| Placebo | Change in ECG | Abnormal (week 0) NCS to abnormal NCS (week 26) | 88 Participants |
| Placebo | Change in ECG | Normal (week 0) to normal (week 26) | 39 Participants |
| Placebo | Change in ECG | Abnormal (week 0) NCS to normal (week 26) | 13 Participants |
| Placebo | Change in ECG | Normal (week 0) to abnormal NCS (week 26) | 9 Participants |
| Placebo | Change in ECG | Abnormal (week 0) NCS to abnormal CS (week 26) | 2 Participants |
| Placebo | Change in ECG | Normal (week 0) to abnormal CS (week 26) | 0 Participants |
| Placebo | Change in ECG | Abnormal (week 0) CS to abnormal NCS (week 26) | 0 Participants |
Secondary
Change in Eye Examination
Participants with eye examination findings, normal, abnormal NCS and abnormal CS at baseline (week -2) and week 26 are presented. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week -2, week 26
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 Eye Examination | Left eye (week 26): Normal | 54 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Right eye (week -2): Normal | 59 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Right eye (week -2): Abnormal NCS | 97 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Left eye (week -2): Abnormal CS | 8 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Right eye (week -2): Abnormal CS | 7 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Left eye (week -2): Normal | 57 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Right eye (week 26): Normal | 52 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Left eye (week 26): Abnormal CS | 5 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Right eye (week 26): Abnormal NCS | 97 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Left eye (week -2): Abnormal NCS | 98 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Right eye (week 26): Abnormal CS | 2 Participants |
| Oral Semaglutide 14 mg | Change in Eye Examination | Left eye (week 26): Abnormal NCS | 92 Participants |
| Placebo | Change in Eye Examination | Right eye (week 26): Abnormal CS | 0 Participants |
| Placebo | Change in Eye Examination | Left eye (week 26): Abnormal NCS | 95 Participants |
| Placebo | Change in Eye Examination | Left eye (week 26): Abnormal CS | 0 Participants |
| Placebo | Change in Eye Examination | Right eye (week -2): Normal | 66 Participants |
| Placebo | Change in Eye Examination | Left eye (week -2): Normal | 66 Participants |
| Placebo | Change in Eye Examination | Left eye (week -2): Abnormal CS | 0 Participants |
| Placebo | Change in Eye Examination | Left eye (week 26): Normal | 55 Participants |
| Placebo | Change in Eye Examination | Right eye (week -2): Abnormal NCS | 93 Participants |
| Placebo | Change in Eye Examination | Right eye (week -2): Abnormal CS | 0 Participants |
| Placebo | Change in Eye Examination | Right eye (week 26): Normal | 55 Participants |
| Placebo | Change in Eye Examination | Right eye (week 26): Abnormal NCS | 95 Participants |
| Placebo | Change in Eye Examination | Left eye (week -2): Abnormal NCS | 93 Participants |
Secondary
Change in FPG
Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in FPG | -1.58 mmol/L | Standard Deviation 2.96 |
| Placebo | Change in FPG | -0.34 mmol/L | Standard Deviation 3.03 |
Secondary
Change in HDL Cholesterol (Ratio to Baseline)
Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at week 26 is presented as ratio to baseline. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in HDL Cholesterol (Ratio to Baseline) | 1.02 Ratio of HDL cholesterol | Geometric Coefficient of Variation 17.5 |
| Placebo | Change in HDL Cholesterol (Ratio to Baseline) | 1.02 Ratio of HDL cholesterol | Geometric Coefficient of Variation 15.4 |
Secondary
Change in LDL Cholesterol (Ratio to Baseline)
Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at week 26 is presented as ratio to baseline. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in LDL Cholesterol (Ratio to Baseline) | 0.97 Ratio of LDL cholesterol | Geometric Coefficient of Variation 32.7 |
| Placebo | Change in LDL Cholesterol (Ratio to Baseline) | 1.00 Ratio of LDL cholesterol | Geometric Coefficient of Variation 38.2 |
Secondary
Change in Lipase (Ratio to Baseline)
Change from baseline (week 0) in lipase (U/L) at week 26 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was 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
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Lipase (Ratio to Baseline) | 1.16 Ratio of lipase | Geometric Coefficient of Variation 57.6 |
| Placebo | Change in Lipase (Ratio to Baseline) | 0.94 Ratio of lipase | Geometric Coefficient of Variation 52.5 |
Secondary
Change in Physical Examination
Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (week \[wk\] -2) and wk 26 are presented. Results are based on the 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 and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system; 2) Nervous system (central and peripheral); 3) Gastrointestinal system, incl. mouth; 4) General appearance; 5) Head (ears, eyes, nose), throat, neck; 6) Lymph node palpation; 7) Musculoskeletal system; 8) Respiratory system; 9) Skin; 10) Thyroid gland.
Time frame: Week -2, week 26
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 Physical Examination | 10) Thyroid gland (wk 26): Abnormal NCS | 12 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 1) Cardiovascular system (wk 26): Normal | 101 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 3) Gastrointestinal system (wk -2): Abnormal NCS | 14 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 7) Musculoskeletal system (wk -2): Normal | 131 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 7) Musculoskeletal system (wk -2): Abnormal NCS | 27 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 8) Respiratory system (wk -2): Abnormal NCS | 9 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 9) Skin (wk -2): Abnormal CS | 1 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 10) Thyroid gland (wk -2): Normal | 150 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 10) Thyroid gland (wk 26): Abnormal CS | 1 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 1) Cardiovascular system (wk -2): Abnormal NCS | 50 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 1) Cardiovascular system (wk -2): Abnormal CS | 6 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 1) Cardiovascular system (wk 26): Abnormal NCS | 48 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 1) Cardiovascular system (wk 26): Abnormal CS | 6 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 2) Nervous system (wk -2): Normal | 114 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 2) Nervous system (wk -2): Abnormal NCS | 41 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 2) Nervous system (wk -2): Abnormal CS | 8 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 2) Nervous system (wk 26): Normal | 109 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 2) Nervous system (wk 26): Abnormal NCS | 40 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 2) Nervous system (wk 26): Abnormal CS | 6 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 3) Gastrointestinal system (wk -2): Normal | 149 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 3) Gastrointestinal system (wk -2): Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 3) Gastrointestinal system (wk 26): Normal | 146 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 3) Gastrointestinal system (wk 26): Abnormal NCS | 9 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 3) Gastrointestinal system (wk 26): Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 4) General appearance (wk -2): Normal | 133 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 4) General appearance (wk -2): Abnormal NCS | 27 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 4) General appearance (wk -2): Abnormal CS | 3 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 4) General appearance (wk 26): Normal | 139 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 4) General appearance (wk 26): Abnormal NCS | 15 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 4) General appearance (wk 26): Abnormal CS | 1 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 5) Head, throat, neck (wk -2): Normal | 151 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 5) Head, throat, neck (wk -2): Abnormal NCS | 10 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 5) Head, throat, neck (wk -2): Abnormal CS | 2 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 5) Head, throat, neck (wk 26): Normal | 142 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 5) Head, throat, neck (wk 26): Abnormal NCS | 10 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 5) Head, throat, neck (wk 26): Abnormal CS | 3 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 6) Lymph node palpation (wk -2): Normal | 161 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 6) Lymph node palpation (wk -2): Abnormal NCS | 1 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 6) Lymph node palpation (wk -2): Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 6) Lymph node palpation (wk 26): Normal | 155 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 6) Lymph node palpation (wk 26): Abnormal NCS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 6) Lymph node palpation (wk 26): Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 7) Musculoskeletal system (wk -2): Abnormal CS | 5 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 7) Musculoskeletal system (wk 26): Normal | 131 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 7) Musculoskeletal system (wk 26): Abnormal NCS | 22 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 7) Musculoskeletal system (wk 26): Abnormal CS | 2 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 8) Respiratory system (wk -2): Normal | 154 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 8) Respiratory system (wk -2): Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 8) Respiratory system (wk 26): Normal | 151 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 8) Respiratory system (wk 26): Abnormal NCS | 4 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 8) Respiratory system (wk 26): Abnormal CS | 0 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 9) Skin (wk -2): Normal | 129 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 9) Skin (wk -2): Abnormal NCS | 33 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 9) Skin (wk 26): Normal | 128 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 9) Skin (wk 26): Abnormal NCS | 23 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 9) Skin (wk 26): Abnormal CS | 4 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 10) Thyroid gland (wk -2): Abnormal NCS | 12 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 10) Thyroid gland (wk -2): Abnormal CS | 1 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 10) Thyroid gland (wk 26): Normal | 142 Participants |
| Oral Semaglutide 14 mg | Change in Physical Examination | 1) Cardiovascular system (wk -2): Normal | 107 Participants |
| Placebo | Change in Physical Examination | 5) Head, throat, neck (wk -2): Abnormal NCS | 15 Participants |
| Placebo | Change in Physical Examination | 1) Cardiovascular system (wk -2): Abnormal NCS | 55 Participants |
| Placebo | Change in Physical Examination | 8) Respiratory system (wk -2): Normal | 150 Participants |
| Placebo | Change in Physical Examination | 2) Nervous system (wk -2): Abnormal NCS | 45 Participants |
| Placebo | Change in Physical Examination | 2) Nervous system (wk 26): Abnormal NCS | 39 Participants |
| Placebo | Change in Physical Examination | 5) Head, throat, neck (wk -2): Abnormal CS | 3 Participants |
| Placebo | Change in Physical Examination | 3) Gastrointestinal system (wk -2): Abnormal NCS | 9 Participants |
| Placebo | Change in Physical Examination | 3) Gastrointestinal system (wk 26): Abnormal CS | 1 Participants |
| Placebo | Change in Physical Examination | 8) Respiratory system (wk -2): Abnormal NCS | 8 Participants |
| Placebo | Change in Physical Examination | 5) Head, throat, neck (wk 26): Normal | 139 Participants |
| Placebo | Change in Physical Examination | 10) Thyroid gland (wk -2): Abnormal CS | 0 Participants |
| Placebo | Change in Physical Examination | 5) Head, throat, neck (wk 26): Abnormal NCS | 11 Participants |
| Placebo | Change in Physical Examination | 8) Respiratory system (wk -2): Abnormal CS | 3 Participants |
| Placebo | Change in Physical Examination | 10) Thyroid gland (wk -2): Normal | 146 Participants |
| Placebo | Change in Physical Examination | 10) Thyroid gland (wk 26): Abnormal NCS | 14 Participants |
| Placebo | Change in Physical Examination | 5) Head, throat, neck (wk 26): Abnormal CS | 3 Participants |
| Placebo | Change in Physical Examination | 10) Thyroid gland (wk 26): Abnormal CS | 0 Participants |
| Placebo | Change in Physical Examination | 1) Cardiovascular system (wk -2): Normal | 103 Participants |
| Placebo | Change in Physical Examination | 9) Skin (wk 26): Normal | 136 Participants |
| Placebo | Change in Physical Examination | 6) Lymph node palpation (wk -2): Normal | 161 Participants |
| Placebo | Change in Physical Examination | 1) Cardiovascular system (wk -2): Abnormal CS | 3 Participants |
| Placebo | Change in Physical Examination | 1) Cardiovascular system (wk 26): Normal | 104 Participants |
| Placebo | Change in Physical Examination | 8) Respiratory system (wk 26): Normal | 147 Participants |
| Placebo | Change in Physical Examination | 1) Cardiovascular system (wk 26): Abnormal NCS | 47 Participants |
| Placebo | Change in Physical Examination | 6) Lymph node palpation (wk -2): Abnormal NCS | 0 Participants |
| Placebo | Change in Physical Examination | 1) Cardiovascular system (wk 26): Abnormal CS | 3 Participants |
| Placebo | Change in Physical Examination | 10) Thyroid gland (wk -2): Abnormal NCS | 15 Participants |
| Placebo | Change in Physical Examination | 2) Nervous system (wk -2): Normal | 116 Participants |
| Placebo | Change in Physical Examination | 6) Lymph node palpation (wk -2): Abnormal CS | 0 Participants |
| Placebo | Change in Physical Examination | 8) Respiratory system (wk 26): Abnormal NCS | 5 Participants |
| Placebo | Change in Physical Examination | 2) Nervous system (wk -2): Abnormal CS | 0 Participants |
| Placebo | Change in Physical Examination | 6) Lymph node palpation (wk 26): Normal | 154 Participants |
| Placebo | Change in Physical Examination | 2) Nervous system (wk 26): Normal | 115 Participants |
| Placebo | Change in Physical Examination | 9) Skin (wk 26): Abnormal NCS | 18 Participants |
| Placebo | Change in Physical Examination | 6) Lymph node palpation (wk 26): Abnormal NCS | 0 Participants |
| Placebo | Change in Physical Examination | 2) Nervous system (wk 26): Abnormal CS | 0 Participants |
| Placebo | Change in Physical Examination | 8) Respiratory system (wk 26): Abnormal CS | 2 Participants |
| Placebo | Change in Physical Examination | 3) Gastrointestinal system (wk -2): Normal | 152 Participants |
| Placebo | Change in Physical Examination | 6) Lymph node palpation (wk 26): Abnormal CS | 0 Participants |
| Placebo | Change in Physical Examination | 3) Gastrointestinal system (wk -2): Abnormal CS | 0 Participants |
| Placebo | Change in Physical Examination | 7) Musculoskeletal system (wk -2): Normal | 135 Participants |
| Placebo | Change in Physical Examination | 3) Gastrointestinal system (wk 26): Normal | 145 Participants |
| Placebo | Change in Physical Examination | 7) Musculoskeletal system (wk -2): Abnormal NCS | 24 Participants |
| Placebo | Change in Physical Examination | 3) Gastrointestinal system (wk 26): Abnormal NCS | 7 Participants |
| Placebo | Change in Physical Examination | 10) Thyroid gland (wk 26): Normal | 140 Participants |
| Placebo | Change in Physical Examination | 7) Musculoskeletal system (wk -2): Abnormal CS | 2 Participants |
| Placebo | Change in Physical Examination | 4) General appearance (wk -2): Normal | 138 Participants |
| Placebo | Change in Physical Examination | 9) Skin (wk -2): Normal | 129 Participants |
| Placebo | Change in Physical Examination | 4) General appearance (wk -2): Abnormal NCS | 20 Participants |
| Placebo | Change in Physical Examination | 7) Musculoskeletal system (wk 26): Normal | 130 Participants |
| Placebo | Change in Physical Examination | 4) General appearance (wk -2): Abnormal CS | 3 Participants |
| Placebo | Change in Physical Examination | 9) Skin (wk 26): Abnormal CS | 0 Participants |
| Placebo | Change in Physical Examination | 4) General appearance (wk 26): Normal | 137 Participants |
| Placebo | Change in Physical Examination | 7) Musculoskeletal system (wk 26): Abnormal NCS | 21 Participants |
| Placebo | Change in Physical Examination | 4) General appearance (wk 26): Abnormal NCS | 16 Participants |
| Placebo | Change in Physical Examination | 9) Skin (wk -2): Abnormal NCS | 32 Participants |
| Placebo | Change in Physical Examination | 4) General appearance (wk 26): Abnormal CS | 1 Participants |
| Placebo | Change in Physical Examination | 7) Musculoskeletal system (wk 26): Abnormal CS | 2 Participants |
| Placebo | Change in Physical Examination | 5) Head, throat, neck (wk -2): Normal | 143 Participants |
| Placebo | Change in Physical Examination | 9) Skin (wk -2): Abnormal CS | 0 Participants |
Secondary
Change in Pulse Rate
Change from baseline (week 0) in pulse rate was evaluated at week 26. Results are based on the data from the on-treatment observation period which was 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
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Pulse Rate | 1 Beats/minute | Standard Deviation 9 |
| Placebo | Change in Pulse Rate | -1 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 week 26. 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
Population: Overall number of participants analyzed = FAS which comprised all randomised participants. 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) | 2) Role functioning | 1.97 Score | Standard Deviation 8.43 |
| 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) | 5) Vitality | 0.05 Score | Standard Deviation 7.53 |
| 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) | 1) Physical functioning | 0.71 Score | Standard Deviation 7.21 |
| 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) | 3) Bodily pain | 3.18 Score | Standard Deviation 10.14 |
| 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) | 4) General health | 0.18 Score | Standard Deviation 6.01 |
| 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) | 6) Social functioning | 1.87 Score | Standard Deviation 7.81 |
| 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) | 7) Role emotional | 0.62 Score | Standard Deviation 10.83 |
| 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) | 8) Mental health | 0.34 Score | Standard Deviation 8.72 |
| 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) | Physical component summary (PCS) | 1.78 Score | Standard Deviation 7.16 |
| 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) | Mental component summary (MCS) | 0.26 Score | Standard Deviation 8.74 |
| Placebo | 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) | 8) Mental health | -0.19 Score | Standard Deviation 9.48 |
| Placebo | 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) | 2) Role functioning | -0.36 Score | Standard Deviation 7.76 |
| Placebo | 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) | 6) Social functioning | -0.06 Score | Standard Deviation 9.64 |
| Placebo | 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) | Mental component summary (MCS) | -0.32 Score | Standard Deviation 10.15 |
| Placebo | 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) | 1) Physical functioning | -0.41 Score | Standard Deviation 6.43 |
| Placebo | 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) | 7) Role emotional | -1.18 Score | Standard Deviation 12.32 |
| Placebo | 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) | 3) Bodily pain | -0.33 Score | Standard Deviation 11.47 |
| Placebo | 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) | Physical component summary (PCS) | -0.15 Score | Standard Deviation 6.1 |
| Placebo | 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) | 4) General health | -0.13 Score | Standard Deviation 5.77 |
| Placebo | 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) | 5) Vitality | 0.56 Score | Standard Deviation 8.02 |
Secondary
Change in Total Cholesterol (Ratio to Baseline)
Change from baseline (week 0) in total cholesterol (mmol/L) at week 26 is presented as ratio to baseline. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Total Cholesterol (Ratio to Baseline) | 0.97 Ratio of total cholesterol | Geometric Coefficient of Variation 20.1 |
| Placebo | Change in Total Cholesterol (Ratio to Baseline) | 1.00 Ratio of total cholesterol | Geometric Coefficient of Variation 23 |
Secondary
Change in Triglycerides (Ratio to Baseline)
Change from baseline (week 0) in triglycerides (mmol/L) at week 26 is presented as ratio to baseline. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Triglycerides (Ratio to Baseline) | 0.87 Ratio of triglycerides | Geometric Coefficient of Variation 37.7 |
| Placebo | Change in Triglycerides (Ratio to Baseline) | 0.95 Ratio of triglycerides | Geometric Coefficient of Variation 37.1 |
Secondary
Change in Urinalysis
Participants with urinalysis, leukocytes and erythrocytes findings, negative, trace, small, moderate or large at baseline (week \[wk\] 0) and wk 26 are presented. Participants with urinalysis, nitrit findings, negative or positive at baseline (wk 0) and wk 26 are presented. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Week -2, week 26
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 Urinalysis | Leucocytes (wk 0): Small | 8 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Leucocytes (wk 26): Negative | 91 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Erythrocytes (wk 0): Negative | 147 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Leucocytes (wk 0): Negative | 121 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Leucocytes (wk 0): Trace | 14 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Leucocytes (wk 0): Moderate | 10 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Leucocytes (wk 0): Large | 5 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Leucocytes (wk 26): Trace | 9 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Leucocytes (wk 26): Small | 13 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Leucocytes (wk 26): Moderate | 10 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Leucocytes (wk 26): Large | 6 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Erythrocytes (wk 0): Trace | 4 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Erythrocytes (wk 0): Small | 4 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Erythrocytes (wk 0): Moderate | 1 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Erythrocytes (wk 0): Large | 2 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Erythrocytes (wk 26): Negative | 115 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Erythrocytes (wk 26): Trace | 6 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Erythrocytes (wk 26): Small | 6 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Erythrocytes (wk 26): Moderate | 2 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Erythrocytes (wk 26): Large | 0 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Nitrit (wk 0): Negative | 149 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Nitrit (wk 0): Positive | 9 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Nitrit (wk 26): Negative | 118 Participants |
| Oral Semaglutide 14 mg | Change in Urinalysis | Nitrit (wk 26): Positive | 11 Participants |
| Placebo | Change in Urinalysis | Nitrit (wk 0): Negative | 146 Participants |
| Placebo | Change in Urinalysis | Leucocytes (wk 0): Small | 12 Participants |
| Placebo | Change in Urinalysis | Erythrocytes (wk 26): Small | 3 Participants |
| Placebo | Change in Urinalysis | Leucocytes (wk 26): Negative | 103 Participants |
| Placebo | Change in Urinalysis | Leucocytes (wk 26): Trace | 11 Participants |
| Placebo | Change in Urinalysis | Leucocytes (wk 26): Large | 4 Participants |
| Placebo | Change in Urinalysis | Erythrocytes (wk 0): Small | 4 Participants |
| Placebo | Change in Urinalysis | Erythrocytes (wk 0): Trace | 10 Participants |
| Placebo | Change in Urinalysis | Erythrocytes (wk 26): Moderate | 4 Participants |
| Placebo | Change in Urinalysis | Nitrit (wk 26): Negative | 126 Participants |
| Placebo | Change in Urinalysis | Leucocytes (wk 0): Negative | 122 Participants |
| Placebo | Change in Urinalysis | Erythrocytes (wk 0): Moderate | 1 Participants |
| Placebo | Change in Urinalysis | Leucocytes (wk 0): Trace | 7 Participants |
| Placebo | Change in Urinalysis | Nitrit (wk 0): Positive | 9 Participants |
| Placebo | Change in Urinalysis | Leucocytes (wk 0): Moderate | 9 Participants |
| Placebo | Change in Urinalysis | Erythrocytes (wk 0): Large | 3 Participants |
| Placebo | Change in Urinalysis | Leucocytes (wk 0): Large | 5 Participants |
| Placebo | Change in Urinalysis | Erythrocytes (wk 26): Large | 2 Participants |
| Placebo | Change in Urinalysis | Erythrocytes (wk 26): Negative | 122 Participants |
| Placebo | Change in Urinalysis | Leucocytes (wk 26): Small | 10 Participants |
| Placebo | Change in Urinalysis | Nitrit (wk 26): Positive | 12 Participants |
| Placebo | Change in Urinalysis | Leucocytes (wk 26): Moderate | 10 Participants |
| Placebo | Change in Urinalysis | Erythrocytes (wk 26): Trace | 7 Participants |
| Placebo | Change in Urinalysis | Erythrocytes (wk 0): Negative | 137 Participants |
Secondary
Change in Urinary Albumin to Creatinine Ratio (Ratio to Baseline)
Change from baseline (week 0) in urinary albumin to creatinine ratio (mg/mmol) at week 26 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was 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
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Urinary Albumin to Creatinine Ratio (Ratio to Baseline) | 0.86 Ratio | Geometric Coefficient of Variation 119.7 |
| Placebo | Change in Urinary Albumin to Creatinine Ratio (Ratio to Baseline) | 1.19 Ratio | Geometric Coefficient of Variation 145.4 |
Secondary
Change in Waist Circumference
Change from baseline (week 0) in waist circumference was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 0, week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Semaglutide 14 mg | Change in Waist Circumference | -2.8 Centimetre (cm) | Standard Deviation 4.9 |
| Placebo | Change in Waist Circumference | -0.7 Centimetre (cm) | Standard Deviation 3.8 |
Secondary
Number of TEAEs
Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Weeks 0-31
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 TEAEs | 463 Events |
| Placebo | Number of TEAEs | 331 Events |
Secondary
Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes
Treatment emergent severe or BG-confirmed symptomatic hypoglycaemic episodes were recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the first dose of trial product until last dose of trial product were considered treatment -emergent. Severe or BG-confirmed symptomatic hypoglycaemia was defined as 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. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Weeks 0-31
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 BG-confirmed Symptomatic Hypoglycaemic Episodes | 17 Episodes |
| Placebo | Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes | 3 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 (weeks 0-31) are presented. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Weeks 0-31
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) | 1 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 (weeks 0-31) are presented. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Weeks 0-31
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) | 1 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 (weeks 0-31) are presented. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Weeks 0-31
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 (weeks 0-31) are presented. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Weeks 0-31
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% (American Association of Clinical Endocrinologists (AACE) target) (yes/no), was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | Yes | 60 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | No | 94 Participants |
| Placebo | Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | Yes | 12 Participants |
| Placebo | Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) | No | 143 Participants |
Secondary
Participants Who Achieve HbA1c <7.0% (53 mmol/Mol), ADA Target (Yes/no)
Participants who achieved HbA1c \<7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c <7.0% (53 mmol/Mol), ADA Target (Yes/no) | Yes | 89 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c <7.0% (53 mmol/Mol), ADA Target (Yes/no) | No | 65 Participants |
| Placebo | Participants Who Achieve HbA1c <7.0% (53 mmol/Mol), ADA Target (Yes/no) | Yes | 35 Participants |
| Placebo | Participants Who Achieve HbA1c <7.0% (53 mmol/Mol), ADA Target (Yes/no) | No | 120 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 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) was evaluated at week 26. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Group | 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) | Yes | 78 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) | No | 76 Participants |
| Placebo | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) | No | 128 Participants |
| Placebo | Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) | Yes | 27 Participants |
Secondary
Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)
Participants who achieved HbA1c reduction ≥1% and weight loss of ≥3% (yes/no) was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | Yes | 60 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | No | 94 Participants |
| Placebo | Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | Yes | 12 Participants |
| Placebo | Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) | No | 143 Participants |
Secondary
Participants Who Achieve Weight Loss ≥10% (Yes/no)
Participants who achieved weight loss of ≥10% of their baseline body weight (yes/no) was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Semaglutide 14 mg | Participants Who Achieve Weight Loss ≥10% (Yes/no) | Yes | 13 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve Weight Loss ≥10% (Yes/no) | No | 141 Participants |
| Placebo | Participants Who Achieve Weight Loss ≥10% (Yes/no) | Yes | 0 Participants |
| Placebo | Participants Who Achieve Weight Loss ≥10% (Yes/no) | No | 155 Participants |
Secondary
Participants Who Achieve Weight Loss ≥5% (Yes/no)
Participants who achieved weight loss ≥5% of their baseline body weight (yes/no) was evaluated at week 26. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Week 26
Population: Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Semaglutide 14 mg | Participants Who Achieve Weight Loss ≥5% (Yes/no) | Yes | 55 Participants |
| Oral Semaglutide 14 mg | Participants Who Achieve Weight Loss ≥5% (Yes/no) | No | 99 Participants |
| Placebo | Participants Who Achieve Weight Loss ≥5% (Yes/no) | Yes | 15 Participants |
| Placebo | Participants Who Achieve Weight Loss ≥5% (Yes/no) | No | 140 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 from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the first dose of trial product until last dose of trial product were considered treatment -emergent. Severe or BG-confirmed symptomatic hypoglycaemia was defined as 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. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Weeks 0-31
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) | 9 Participants |
| Placebo | Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no) | 3 Participants |
Secondary
Semaglutide Plasma Concentrations for Population PK Analyses
This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Semaglutide plasma concentrations were measured at weeks 4, 8, 14 and 26. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Weeks 0-26
Population: Overall number of participants analyzed = FAS which comprised all randomised participants. 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 | 1.8 Nanomoles per litre (nmol/L) | Geometric Coefficient of Variation 113.5 |
| Oral Semaglutide 14 mg | Semaglutide Plasma Concentrations for Population PK Analyses | Week 8 | 5.2 Nanomoles per litre (nmol/L) | Geometric Coefficient of Variation 143.4 |
| Oral Semaglutide 14 mg | Semaglutide Plasma Concentrations for Population PK Analyses | Week 14 | 9.4 Nanomoles per litre (nmol/L) | Geometric Coefficient of Variation 206.6 |
| Oral Semaglutide 14 mg | Semaglutide Plasma Concentrations for Population PK Analyses | Week 26 | 6.9 Nanomoles per litre (nmol/L) | Geometric Coefficient of Variation 251.3 |
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 weeks 4, 14 and 26. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time frame: Weeks 0-26
Population: Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oral Semaglutide 14 mg | SNAC Plasma Concentrations | Week 4: 40 minutes post-dose | 364 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 308.5 |
| Oral Semaglutide 14 mg | SNAC Plasma Concentrations | Week 14: 25 minutes post-dose | 418 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 389.7 |
| Oral Semaglutide 14 mg | SNAC Plasma Concentrations | Week 4: 25 minutes post-dose | 578 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 347.4 |
| Oral Semaglutide 14 mg | SNAC Plasma Concentrations | Week 14: 40 minutes post-dose | 330 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 349.2 |
| Oral Semaglutide 14 mg | SNAC Plasma Concentrations | Week 26: 25 minutes post-dose | 435 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 688 |
| Oral Semaglutide 14 mg | SNAC Plasma Concentrations | Week 26: 40 minutes post-dose | 288 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 596.1 |
Secondary
Time to Additional Anti-diabetic Medication
Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the period, from week 0 to week 26. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 26), 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. Results are based on the 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 and/or premature discontinuation of trial product.
Time frame: Weeks 0-26
Population: Overall number of participants analyzed = FAS which comprised all randomised participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Semaglutide 14 mg | Time to Additional Anti-diabetic Medication | 12 Participants |
| Placebo | Time to Additional Anti-diabetic Medication | 21 Participants |
Comparison: Time to initiation of additional anti-diabetic medication was analysed using a Cox proportional hazards model with treatment, strata, interaction strata, 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: =0.183495% CI: [0.34, 1.23]Regression, Cox
Secondary
Time to Rescue Medication
Presented results are the number of participants who had taken rescue medication anytime during the period, from week 0 to week 26. Rescue medication was defined as any new anti-diabetic medication used 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, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time frame: Weeks 0-26
Population: Overall number of participants analyzed = FAS which comprised all randomised participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Semaglutide 14 mg | Time to Rescue Medication | 7 Participants |
| Placebo | Time to Rescue Medication | 16 Participants |
Comparison: Time to initiation of rescue medication was analysed using a Cox proportional hazards model with treatment, strata, interaction strata, and region as categorical fixed effects and baseline HbA1c as covariate. Censoring time was one day before last day on trial product.p-value: =0.06195% CI: [0.17, 1.04]Regression, Cox