New Phase 3 Trials Investigate Survodutide as a Promising Treatment for Obesity

Researchers have launched 2 multinational phase 3 clinical trials to evaluate the efficacy and safety of the novel dual glucagon-like peptide 1 receptor (GLP-1R)/glucagon receptor (GCGR) agonist survodutide (Boehringer Ingelheim).

The 2 pivotal trials—SYNCHRONIZE-1 and -2—aim to provide robust evidence on the potential of survodutide to aid weight loss and improve metabolic health in individuals with obesity, with or without type 2 diabetes (T2D), according to a new article detailing the rationale and design of the studies.

“The World Obesity Federation estimated that 988 million people worldwide had obesity (defined as BMI ≥30 kg/m2) in 2020, representing 14% of the global population at the time. It predicted an increase to ~1.9 billion (24%) by 2035,” corresponding author Sean Wharton, MD, PharmD, adjunct professor, McMaster University, Hamilton, Ontario, Canada, and colleagues wrote in the journal Obesity.

They continued: “Antiobesity medications (AOMs) in conjunction with lifestyle changes are recommended for the treatment of obesity, but only a few AOMs are available to combat this highly prevalent and heterogenous disease.”

Survodutide is currently under investigation for the treatment of obesity and its complications, including metabolic dysfunction-associated steatohepatitis (MASH). The drug offers a novel approach to weight management by targeting both glucagon and GLP-1 receptors.

“Concurrent activation of both the glucagon and GLP-1 signaling pathways is hypothesized to provide additional clinical benefits for managing obesity beyond greater weight reduction, owing to the role of glucagon in reducing energy intake, increasing energy expenditure, and directly reducing hepatic fat content,” Wharton and coauthors said. These effects have been demonstrated in earlier phase 2 trials, they added.

Preliminary results from one trial of 295 adults with MASH showed that 83% of survodutide-treated participants showed improvement in MASH with no worsening in fibrosis. In another study of 387 adults with overweight or obesity without T2D, survodutide elicited dose-dependent mean reductions in body weight of up to 18.7% after 46 weeks compared with placebo.

“Based on these promising preliminary results, a comprehensive phase 3 clinical development program is evaluating survodutide for treating obesity,” investigators wrote.

The SYNCHRONIZE clinical trials are 76-week, multinational, randomized, double-blind, placebo-controlled studies in which participants receive once-weekly subcutaneous injections of survodutide or placebo, alongside lifestyle modifications. One of the key features of these trials is the flexible dosing strategy. Participants will be uptitrated to doses of 3.6 mg or 6.0 mg of survodutide, with the option to temporarily halt dosing for those experiencing severe gastrointestinal (GI) adverse events. This approach aims to mitigate the likelihood of GI symptoms, “which contribute significantly to discontinuation of medications with GLP-1 receptor agonist activity in clinical practice,” Wharton et al wrote.

The SYNCHRONIZE-1 trial focuses on people with a BMI of ≥30 kg/m² or ≥27 kg/m² with at least 1 obesity-related complication but without T2D (n=726). In contrast, SYNCHRONIZE-2 includes individuals with a BMI of ≥27 kg/m² who also have T2D (n=755), according to investigators. A SYNCHRONIZE-1 substudy is examining changes in body composition and liver fat content using magnetic resonance imaging.

The primary endpoints of both studies include the percentage change in body weight from baseline and the proportion of adults achieving a ≥5% reduction in body weight from baseline to week 76. Secondary endpoints will assess changes in systolic blood pressure and glycemic measures. Researchers also noted that safety and tolerability will be assessed based on reported adverse events, physical examinations, vital signs, laboratory tests, and 12-lead electrocardiograms.

Investigators estimate that SYNCHRONIZE-1 and -2 will be completed in early 2026, with analyzed results available later in 2026.

“The results of the SYNCHRONIZE-1 and -2 trials of the glucagon/GLP-1 receptor dual agonist survodutide will provide data on the efficacy, safety, and tolerability of this molecule, informing its potential clinical role for the treatment of obesity and its many complications,” researchers concluded.

Reference: Wharton S, le Roux CW, Kosiborod MN, et al. Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™-1 and -2). Obesity. Published online November 4, 2024. doi:10.1002/oby.24184