Diabetes Mellitus, Type 2
Conditions
Brief summary
This study compares the medicines semaglutide with empagliflozin or metformin in people with newly diagnosed type 2 diabetes. This study will look mainly at how well participant's blood sugar and body weight are controlled when they are taking the study medicines. Participants will either get semaglutide tablets, empagliflozin tablets or metformin tablets. Which treatment participants will get is decided by chance. Currently, doses of 3 milligram (mg), 7 mg and 14 mg semaglutide tablets (Rybelsus) can be prescribed in some countries. 25 mg and 50 mg semaglutide tablets are new doses. 10 mg and 25 mg empagliflozin tablets (Jardiance) can be prescribed in some countries. 500 mg metformin tablets (STADA) can be prescribed in some countries. Participants will get 1 to 4 tablets per day for 104 weeks. The study will last for about 2 years and 7 weeks (111 weeks). Participants should not have been treated for weight management 90 days before screening or never been treated with any medicine for type 2 diabetes (except diabetes during pregnancy) before screening. Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.
Interventions
DRUGSemaglutide
Administered as oral tablets.
DRUGEmpagliflozin
Administered as oral tablets.
DRUGMetformin
Administered as oral tablets.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male or female. * Age ≥18 and \<60 years at the time of signing the informed consent. * Diagnosed with type 2 diabetes mellitus within 24 months from the day of screening. * HbA1c of 7.0-10.0% (53-86 millimoles per mole \[mmol/mol\]) * Body mass index ≥25.0 kilogram per square meter (kg/m\^2)
Exclusion criteria
* Treatment with any medication for the indication of diabetes. Prior insulin treatment for gestational diabetes is allowed. * Treatment with any medication for the indication of weight management 90 days prior to screening. * Renal impairment measured as estimated glomerular filtration rate (eGFR) \<60 milliliters per minute per 1.73 meter sqaure (mL/min/1.73 m\^2) at screening. * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination. * C-peptide \<1.5 nanograms per milliliter (ng/mL) at screening. * Positive insulinoma associated-protein 2 (IA-2) antibodies ≥7.5 Units/mL or anti-glutamic acid decarboxylase (anti-GAD) antibodies greater than (\>) 5.0 international units per milliliter (IU/mL). * Impaired liver function, defined as Alanine aminotransferase (ALT) ≥2.5 times or Bilirubin \>1.5 times upper normal limit at screening. * History of major surgical procedures involving the stomach potentially affecting absorption of trial products (example subtotal or total gastrectomy, sleeve gastrectomy, gastric bypass surgery) or current presence of gastrointestinal implant. * Presence of clinically significant gastrointestinal disorders affecting absorption of drugs and/or nutrients, as judged by the investigator. * Any contraindications for empagliflozin or metformin according to local labelling at the investigator's discretion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in glycated haemoglobin (HbA1c) | From randomisation (week 0) to week 52 | Measured in Percentage (%)-points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in fasting plasma glucose (FPG) | From randomisation (week 0) to week 52 | Measured in millimoles per liter (mmol/L). |
| Change in 7 point self measured plasma glucose (SMPG) mean profile | From randomisation (week 0) to week 52 | Measured in mmol/L. |
| Change in 7-point self-measured plasma glucose (SMPG) mean post prandial increments | From randomisation (week 0) to week 52 | Measured in mmol/L. |
| Relative change in body weight | From randomisation (week 0) to week 52 | Measured in Percentage (%). |
| Change in waist circumference | From randomisation (week 0) to week 52 | Measured in centimeters (cm). |
| HbA1c less than or equal to (≤) 6.5% (Yes/No) | At week 52 | Measured as count of participants. |
| HbA1c less than (<) 7% (Yes/No) | At week 52 | Measured as count of participants. |
| Body weight reduction greater than equal to ( ≥) 5% (Yes/No) | At week 52 | Measured as count of participants. |
| Body weight reduction ≥10% (Yes/No) | At week 52 | Measured as count of participants. |
| Body weight reduction ≥15% (Yes/No) | At week 52 | Measured as count of participants. |
| HbA1c <7.0% and body weight reduction ≥5% (Yes/No) | At week 52 | Measured as count of participants. |
| Change in systolic blood pressure | From randomisation (week 0) to week 52 | Measured in millimeters of mercury (mmHg). |
| Change in diastolic blood pressure | From randomisation (week 0) to week 52 | Measured in mmHg. |
| Change in High-sensitivity C-reactive protein (hsCRP) | From randomisation (week 0) to week 52 | Measured in milligrams per liter (mg/L). |
| Time to rescue medication | From randomisation (week 0) to week 104 | Measured in days. |
| Change in HbA1c | From randomisation (week 0) to week 104 | Measured in %-points. |
| Change in body weight | From randomisation (week 0) to week 52 | Measured in kilograms (kg). |
| Change in 7 point SMPG mean profile | From randomisation (week 0) to week 104 | Measured in mmol/L. |
| Change in 7-point SMPG mean post prandial increments | From randomisation (week 0) to week 104 | Measured in mmol/L |
| HbA1c ≤6.5% (Yes/No) | At week 104 | Measured as count of participants. |
| HbA1c <7.0% (Yes/No) | At week 104 | Measured as count of participants. |
| Body weight reduction ≥5% (Yes/No) | At week 104 | Measured as count of participants. |
| Change in hsCRP | From randomisation (week 0) to week 104 | Measured in mg/L. |
| Treatment emergent adverse events | From randomisation (week 0) to week 52 | Measured as count of events. |
| Number of severe (level 3) or clinically significant (level 2) hypoglycaemic episodes | From randomisation (week 0) to week 52 | Measured as count of episodes. |
| Change in Control of Eating Questionnaire (CoEQ) score - Craving Control domain | From randomisation (week 0) to week 52 | CoEQ is a 19-item multidimensional patient reported outcome (PRO) that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving control subscale, the subscale score is reversed so that a higher score represents a greater level of craving control. |
| Change in CoEQ score - Craving for Savory domain | From randomisation (week 0) to week 52 | CoEQ is a 19-item multidimensional PRO that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving savoury food subscale, higher score represents a greater level of craving. |
| Change in Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) score - Physical function domain | From randomisation (week 0) to week 52 | IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. Higher scores indicate better levels of functioning. Composite scores (score range): Physical composite (0-100), Psychosocial composite (0 100), Physical Function composite (0-100). Total score range (0-100). |
| Change in American Heart Association (AHA) Life's Simple 7 summary score | From randomisation (week 0) to week 52 | The AHA recommends focusing on 7 cardiovascular health factors (smoking, BMI, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) for early or primary prevention of cardiovascular disease. The 7 health factors are each categorized as ideal, intermediate, or poor. Scales range from 0 (minimum) to 14 (maximum). Higher score represents a greater level of health. |
| Change in CoEQ score - Craving Control domain | From randomisation (week 0) to week 104 | CoEQ is a 19-item multidimensional PRO that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving control subscale, the subscale score is reversed so that a higher score represents a greater level of craving control. |
| Change in IWQOL-Lite-CT score - Physical function domain | From randomisation (week 0) to week 104 | IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. Higher scores indicate better levels of functioning. Composite scores (score range): Physical composite (0-100), Psychosocial composite (0 100), Physical Function composite (0-100). Total score range (0-100). |
| Change in AHA Life's Simple 7 summary score | From randomisation (week 0) to week 104 | The AHA recommends focusing on 7 cardiovascular health factors (smoking, BMI, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) for early or primary prevention of cardiovascular disease. The 7 health factors are each categorized as ideal, intermediate, or poor. Scales range from 0 (minimum) to 14 (maximum). Higher score represents a greater level of health. |
| Change in FPG | From randomisation (week 0) to week 104 | Measured in mmol/L. |
Countries
Brazil, Bulgaria, Croatia, Greece, Hungary, India, Malaysia, Mexico, Poland, Romania, Serbia, Thailand, United States
Outcome results
None listed