Survodutide Achieves Significant Weight Loss and HbA1c Reduction in Adults With Obesity and Type 2 Diabetes: SYNCHRONIZE-2 Trial
Canada: The investigational dual GIP/GLP-1 agonist survodutide demonstrated significant weight loss and improvements in glycaemic control among adults with obesity and type 2 diabetes in the phase III SYNCHRONIZE-2 trial, although tolerability remains a concern.
"At week 76, participants receiving survodutide 3.6 mg and 6 mg achieved mean weight reductions of 8.2% and 9.8%, respectively, compared with 3.9% with placebo. Weight loss of at least 5% was achieved by 57.6%, 64.5%, and 35.1% of participants, respectively," the researchers reported in The New England Journal of Medicine.
Obesity and type 2 diabetes frequently occur together, and effective weight management can substantially influence metabolic health. Survodutide is an investigational glucagon receptor–GLP-1 receptor dual agonist being studied for its potential effects on body weight and glycaemic control.
Sean Wharton, McMaster University, Hamilton, ON, Canada, and colleagues conducted a multinational, double-blind, phase III trial among adults with type 2 diabetes and a body-mass index (BMI) of at least 27. Participants were randomly assigned in a 1:1:1 ratio to receive once-weekly subcutaneous survodutide at doses of 3.6 mg or 6 mg, or placebo.
The two primary outcomes were percentage change in body weight and achievement of at least 5% weight loss from baseline through week 76.
A total of 752 participants were included, with 250 assigned to the 3.6-mg group, 251 to the 6-mg group and 251 to placebo. The mean age was 55.7 years, mean BMI was 36.5, and 49.3% of participants were men.
Key findings included:
- Mean body weight decreased by 8.2% with survodutide 3.6 mg and 9.8% with 6 mg, compared with 3.9% with placebo at week 76.
- Weight loss of at least 5% occurred in 57.6% and 64.5% of participants receiving the 3.6-mg and 6-mg doses, respectively, versus 35.1% with placebo.
- Glycated haemoglobin (HbA1c) declined by 0.9 percentage points with 3.6 mg and 0.8 percentage points with 6 mg, compared with a 0.2 percentage-point reduction with placebo.
- Gastrointestinal adverse events were the most frequently reported side effects, occurring in 72.8% of participants receiving 3.6 mg, 77.7% receiving 6 mg, and 38.6% receiving placebo.
- Gastrointestinal events were generally described as mild to moderate and transient.
The weight-loss analysis used a treatment-regimen estimand, assessing outcomes regardless of whether participants discontinued or interrupted the assigned treatment or used other anti-obesity therapies.
The findings showed that both survodutide doses produced significantly greater weight reduction than placebo among adults with obesity and type 2 diabetes. However, the higher frequency of gastrointestinal adverse events with survodutide highlights tolerability as an important consideration.
Overall, weekly survodutide at 3.6 mg or 6 mg was associated with significant reductions in body weight and HbA1c compared with placebo over 76 weeks in adults with obesity and type 2 diabetes.
Reference:
DOI: 10.1056/NEJMoa2607219
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