Phase 3
N=512
A Research Study to See How Semaglutide Helps People With Excess Weight and Type 2 Diabetes Lose Weight
Obesity · Diabetes Mellitus, Type 2
Bottom Line
View on ClinicalTrials.gov: NCT05649137 ↗Enrolled (actual)
512
Serious AEs
10.0%
Results posted
Apr 2026
Primary outcome: Primary: Relative Change in Body Weight — -13.5; -10.7; -4.0 Percentage (%) change in body weight — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Semaglutide (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novo Nordisk A/S
- Primary completion
- Oct 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Relative Change in Body Weight |
-13.5; -10.7; -4.0 | <0.0001 sig |
| PRIMARY Number of Participants Who Achieve Body Weight Reduction Greater Than or Equal to (>=) 5% (Yes/no) |
251; 73; 33; 40; 24; 62 | <0.0001 sig |
| SECONDARY Number of Participants Who Achieve Body Weight Reduction >= 10% (Yes/no) |
183; 50; 11; 108; 47; 84 | — |
| SECONDARY Number of Participants Who Achieve Body Weight Reduction >= 15% (Yes/no) |
120; 28; 7; 171; 69; 88 | — |
| SECONDARY Number of Participants Who Achieve Body Weight Reduction >= 20% (Yes/no) |
62; 14; 2; 229; 83; 93 | — |
| SECONDARY Change in Waist Circumference |
-12.6; -10.6; -6.5 | — |
| SECONDARY Change in Glycated Haemoglobin (HbA1c) |
-1.8; -1.7; -0.3 | — |
| SECONDARY Change in Body Weight |
-14.9; -11.4; -4.6 | — |
| SECONDARY Change in Body Mass Index (BMI) |
-5.3; -4.1; -1.6 | — |
| SECONDARY Change in Systolic Blood Pressure |
-8; -7; -3 | — |
| SECONDARY Change in Diastolic Blood Pressure |
-3; -3; -3 | — |
| SECONDARY Change in Total Cholesterol (Millimoles Per Liter [mmol/L]) - Ratio to Baseline |
0.96; 0.96; 0.97 | — |
| SECONDARY Change in Total Cholesterol (Milligrams Per Deciliter [mg/dL]) - Ratio to Baseline |
0.96; 0.96; 0.97 | — |
| SECONDARY Change in High-density Lipoprotein (HDL) Cholesterol (mmol/L) - Ratio to Baseline |
1.10; 1.06; 1.07 | — |
| SECONDARY Change in HDL Cholesterol (mg/dL) - Ratio to Baseline |
1.10; 1.06; 1.07 | — |
| SECONDARY Change in Low-density Lipoprotein (LDL) Cholesterol (mmol/L) - Ratio to Baseline |
0.99; 0.95; 0.97 | — |
| SECONDARY Change in LDL Cholesterol (mg/dL) - Ratio to Baseline |
0.99; 0.95; 0.97 | — |
| SECONDARY Change in Very-low-density Lipoprotein (VLDL) Cholesterol (mmol/L) - Ratio to Baseline |
0.72; 0.81; 0.90 | — |
| SECONDARY Change in VLDL Cholesterol (mg/dL) - Ratio to Baseline |
0.72; 0.81; 0.90 | — |
| SECONDARY Change in Triglycerides (mmol/L) - Ratio to Baseline |
0.71; 0.80; 0.87 | — |
| SECONDARY Change in Triglycerides (mg/dL) - Ratio to Baseline |
0.71; 0.80; 0.87 | — |
| SECONDARY Change in Free Fatty Acids (mmol/L) - Ratio to Baseline |
0.74; 0.81; 0.98 | — |
| SECONDARY Change in Free Fatty Acids (mg/dL) - Ratio to Baseline |
0.74; 0.81; 0.98 | — |
| SECONDARY Change in High-sensitivity C-reactive Protein (hsCRP) - Ratio to Baseline |
0.47; 0.48; 0.82 | — |
| SECONDARY Change in Fasting Plasma Glucose |
-59.6; -58.4; -20.2 | — |
| SECONDARY Change in Fasting Serum Insulin (Picomoles Per Liter [Pmol/L]) - Ratio to Baseline |
0.77; 0.90; 0.87 | — |
| SECONDARY Change in Fasting Serum Insulin (Milliinternational Units Per Milliliter [mIU/mL]) - Ratio to Baseline |
0.77; 0.90; 0.87 | — |
| SECONDARY Number of Participants With HbA1c Less Than 7.0 % (53 Millimoles Per Mole [mmol/Mol]) |
235; 75; 27 | — |
| SECONDARY Number of Participants With HbA1c Less Than or Equal to 6.5% (48 mmol/Mol) |
209; 64; 15 | — |
| SECONDARY Semaglutide 7.2 mg Versus Placebo: Number of Adverse Events (AEs) |
1581; 253 | — |
| SECONDARY Semaglutide 7.2 mg Versus Placebo: Number of Serious Adverse Events (SAEs) |
39; 21 | — |
| SECONDARY Change in Pulse |
1; 2; -4 | — |
| SECONDARY Semaglutide 7.2 mg Versus Placebo: Number of Treatment Emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes |
0; 1 | — |
| SECONDARY Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of AEs |
1581; 508 | — |
| SECONDARY Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of SAEs |
39; 35 | — |
| SECONDARY Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of Treatment Emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes |
0; 0 | — |
Summary
This study will look at how much weight participants will lose and how much blood sugar control they achieve from the start to the end of the study. The weight loss in participants taking the investigational high dose of semaglutide will be compared to the weight loss in people taking "dummy" medicine and a lower dose of semaglutide. In addition to taking the medicine, participants will have talks with study staff about healthy food choices and how to be more physically active. Participants will either get semaglutide or "dummy" medicine. Which treatment participants get is decided by chance. Participants are more likely (4 out of 5) to get semaglutide than the "dummy" medicine. The study medicine will be injected briefly, under skin, with a thin needle, typically in the stomach, thighs, or upper arms. After receiving first dose, the dose of semaglutide will be gradually increased until reaching the target dose. The study will last for about 1.5 years
Eligibility Criteria
Inclusion Criteria
- Male or female.
- Age above or equal to 18 years at the time of signing informed consent.
- BMI greater than or equal to 30.0 kilograms per square meter (kg/m^2).
- Diagnosed with type 2 diabetes (T2D) greater than or equal to 180 days prior to the day of screening.
- History of at least one self-reported unsuccessful dietary effort to lose body weight.
- HbA1c 7.0-10.0 percent (53-86 millimoles per mole [mmol/mol]) (both inclusive) as measured by central laboratory at screening.
Exclusion Criteria
- A self-reported change in body weight greater than 5 kilograms (kg) (11 pounds [lbs]) within 90 days before screening irrespective of medical records.
- Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
- Renal impairment with estimated Glomerular Filtration Rate (eGFR) less than 30 milliliters per minute per 1.73 square meter (30 mL/min/1.73 m^2) (less than 45 mL/min/1.73 m^2 in participants treated with Sodium-glucose Cotransporter-2 [SGLT2i]) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 by the central laboratory 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 randomization. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
Data sourced from ClinicalTrials.gov (NCT05649137). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.