Boehringer Ingelheim reported that its Phase III SYNCHRONIZE-2 trial of survodutide, a glucagon/GLP-1 receptor dual agonist, met both co-primary endpoints in adults with obesity or overweight and type 2 diabetes (T2D), producing up to 13.1% mean weight loss versus 3.1% on placebo after 76 weeks.
Weight loss in people with T2D is typically harder to achieve than in those without the condition, making the SYNCHRONIZE-2 population a more demanding test than the non-diabetic SYNCHRONIZE-1 cohort, which produced up to 16.6% weight loss in an earlier readout. The results were presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes and simultaneously published in The New England Journal of Medicine.
SYNCHRONIZE-2 enrolled 755 adults in a double-blind, placebo-controlled design; participants received weekly subcutaneous survodutide at 3.6 mg or 6.0 mg, or placebo, over 76 weeks, with both co-primary endpoints assessed using an efficacy estimand that assumes patients remained on treatment throughout. Up to 79.3% of survodutide-treated participants achieved at least 5% body weight reduction versus 32.7% on placebo (p<0.0001). Key secondary results included an HbA1c reduction of up to 1.21% from a baseline of 7.4% versus 0.03% on placebo, and up to 29.5% of survodutide-treated participants reverted to normoglycemia versus 4.0% on placebo.
Gastrointestinal events were the most common adverse events, consistent with the GLP-1 class; treatment discontinuation due to gastrointestinal adverse events was 18% in the survodutide arm versus 1.2% on placebo, with most discontinuations occurring during dose escalation.
In the same indication at Phase III, Eli Lilly and Company's retatrutide, a GLP-1/GIP/glucagon receptor triple agonist, reported 20.8% weight loss over 80 weeks in the TRIUMPH-2 trial, with the proviso that cross-trial comparisons are limited by differences in population, duration, and design.