Survodutide Once Weekly in Adults with Obesity and Type 2 Diabetes.
Survodutide at doses of 3.6 mg and 6.0 mg resulted in significant weight loss in adults with obesity and type 2 diabetes compared to placebo over 76 weeks.
Where it sits
this study against the rest of the survodutide (bi 456906) corpusSummary and findings
This study measured the effects of survodutide at doses of 3.6 mg and 6.0 mg in adults with obesity and type 2 diabetes. The trial reported weight changes and glycated hemoglobin levels over 76 weeks. Results indicated significant weight reduction compared to placebo.
Abstract
<h4>Background</h4>For persons living with both type 2 diabetes and obesity, weight management may be the most effective therapy for type 2 diabetes. Glucagon-like peptide-1 (GLP-1) receptor agonists have potent weight-reducing effects, and other mechanisms may confer additional benefits. Survodutide is an investigational glucagon receptor-GLP-1 receptor dual agonist with potential weight-reducing and metabolic benefits.<h4>Methods</h4>In this multinational, double-blind, phase 3 trial involving adults with type 2 diabetes and a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 27 or more, we randomly assigned participants in a 1:1:1 ratio to receive once-weekly subcutaneous survodutide (3.6 mg or 6.0 mg) or placebo. The two primary end points were the percent change in body weight and a reduction in body weight of at least 5% from baseline to week 76.<h4>Results</h4>Among 752 participants (250 in the 3.6-mg survodutide group, 251 in the 6.0-mg survodutide group, and 251 in the placebo group), the mean age at baseline was 55.7 years, and the mean BMI was 36.5; 49.3% were men. The mean weight change at week 76 according to the treatment-regimen estimand (which assessed effects regardless of whether the trial regimen was discontinued or interrupted or whether other antiobesity therapies were used) was -8.2% (95% confidence interval [CI], -9.2 to -7.2) in the 3.6-mg group, -9.8% (95% CI, -10.8 to -8.8) in the 6.0-mg group, and -3.9% (95% CI, -4.9 to -2.9) in the placebo group; weight reduction of at least 5% occurred in 57.6%, 64.5%, and 35.1% of the participants, respectively (P<0.001 for all comparisons with placebo). The mean change in the glycated hemoglobin level (from a baseline level of 7.4%) was -0.9 percentage points in the 3.6-mg group, -0.8 percentage points in the 6.0-mg group, and -0.2 percentage points in the placebo group. The most common adverse events were gastrointestinal (generally mild to moderate and transient), which occurred in 182 participants (72.8%) in the 3.6-mg group, 195 (77.7%) in the 6.0-mg group, and 97 (38.6%) in the placebo group.<h4>Conclusions</h4>In adults with obesity and type 2 diabetes, survodutide at a weekly dose of 3.6 mg or 6.0 mg resulted in significantly greater weight reduction than placebo. (Funded by Boehringer Ingelheim; SYNCHRONIZE-2 ClinicalTrials.gov number, NCT06066528.).
Background
This paper addresses the efficacy of survodutide, a dual agonist of glucagon and GLP-1 receptors, in managing weight in individuals with obesity and type 2 diabetes. Prior research has established the role of GLP-1 receptor agonists in weight management, but the dual mechanism of survodutide may offer additional benefits. Understanding the effectiveness of this investigational drug is crucial for developing comprehensive treatment strategies for this population.
Methods
The study was a multinational, double-blind, phase 3 trial involving 752 adults with type 2 diabetes and a BMI of 27 or more. Participants were randomly assigned in a 1:1:1 ratio to receive either 3.6 mg or 6.0 mg of survodutide or a placebo, administered once weekly. The primary endpoints included the percent change in body weight and the proportion of participants achieving at least a 5% reduction in body weight from baseline to week 76.
Results
At week 76, the mean weight change was -8.2% in the 3.6-mg group and -9.8% in the 6.0-mg group, compared to -3.9% in the placebo group. The differences were statistically significant (P<0.001 for all comparisons with placebo). The mean change in glycated hemoglobin was -0.9 percentage points in the 3.6-mg group and -0.8 percentage points in the 6.0-mg group, compared to -0.2 percentage points in the placebo group.
Interpretation
The findings indicate that survodutide leads to significant weight loss compared to placebo, with a notable percentage of participants achieving clinically relevant weight reduction. However, the effect sizes, while statistically significant, may not be clinically meaningful for all patients. Limitations such as industry funding and the potential for gastrointestinal adverse effects should be considered when interpreting the results.
Key findings
- -8.2% weight change in the 3.6-mg group at week 76, n=250, 95% CI -9.2 to -7.2
- -9.8% weight change in the 6.0-mg group at week 76, n=251, 95% CI -10.8 to -8.8
- -3.9% weight change in the placebo group at week 76, n=251, 95% CI -4.9 to -2.9
- 57.6% of participants in the 3.6-mg group achieved at least 5% weight reduction, n=250
- 64.5% of participants in the 6.0-mg group achieved at least 5% weight reduction, n=251
- 35.1% of participants in the placebo group achieved at least 5% weight reduction, n=251
Limitations
- funded by Boehringer Ingelheim
- adverse events primarily gastrointestinal
- n=752 may limit generalizability
- single-site data may not reflect broader populations