In two phase 3 trials, survodutide significantly reduced body weight and liver fat and improved markers of metabolic health.

These findings, from SYNCHRONIZE-1 and SYNCHRONIZE-MASLD, were shared on Sunday, June 7 during The Benefits of Glucagon/GLP-1 Receptor Dual Agonism: Insights from the SYNCHRONIZE™ Phase 3 Studies of Survodutide. On-demand access to recorded presentations will be available to registered participants following the conclusion of the 2026 Scientific Sessions, from June 10–August 10.

“When you look at the various polyagonists of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon, it seems there are a number of side effects that likely have to do with activating the GLP-1 receptor. So the provocative idea is, what if we get rid of GLP-1? What if there was a dual agonist that consisted only of GIP and glucagon?” said Matthias H. Tschöp, MD, President of Ludwig-Maximilian-University of Munich, Germany.

This question drove the development of survodutide, a glucagon/GLP-1 dual receptor agonist, which is now being studied in a global phase 3 program.

SYNCHRONIZE-1

“Survodutide is an effective treatment for obesity with sustained weight reductions of up to 16.6%. The body weight reduction with survodutide was driven predominantly by loss of fat tissue,” said Carel le Roux, MBChB, FRCP, FRCPath, PhD, Professor and Director of the Metabolic Medicine Group at University College Dublin, Ireland.

He reported on SYNCHRONIZE-1, a randomized, double-blind, placebo-controlled phase 3 obesity trial that assessed the efficacy and safety of survodutide in adults with a body mass index (BMI) over 30, or over 27 with one metabolic condition excluding diabetes. Additionally, participants had to have at least one self-reported unsuccessful dietary effort to lose weight.

The 726 participants were randomized to placebo or survodutide, either a 3.6 mg or 6 mg dose, and all received nutritional and physical activity counseling. The primary endpoints were percentage change in body weight and body weight reduction ≥5% at week 76.

“The reduction in visceral and liver fat and improvements in glucose and lipid metabolism demonstrate the broad benefit of survodutide at improving metabolic health,” Dr. le Roux noted.

There were two notable findings regarding the placebo group in this study. First, more than 16.5% of participants in the placebo group were using prohibited medication containing GLP-1 receptor agonists. Second was the treatment completion rate in the placebo group.

“Nearly 60% of the placebo group completed treatment, with nearly 88% completing the trial,” reported Ania M. Jastreboff, MD, PhD, Professor at Yale University School and Director of the Y-Weight Obesity Research Center. “In terms of placebo, it’s becoming increasingly challenging to keep participants on treatment, given that they seek out other forms of treatment when they realize they are not losing weight.”

SYNCHRONIZE-MASLD

SYNCHRONIZE-MASLD was a 48-week randomized, double-blind, placebo-controlled phase 3 obesity trial that assessed the efficacy and safety of survodutide in adults with obesity and at-risk metabolic dysfunction-associated steatotic liver disease (MASLD). The trial was similar to SYNCHRONIZE-1 but had a shorter duration of 48 weeks and had only two arms: placebo and 6 mg of survodutide. The primary endpoints were relative reduction in liver fat content of ≥30% and percentage change in body weight.

“Survodutide significantly reduced body weight and improved cardiovascular and cardiometabolic parameters. Survodutide significantly reduced liver fat content and markers of all components of MALD, including fat content, injury, inflammation, and fibrosis,” said Lee M.  Kaplan, MD, PhD, Director of the Obesity and Metabolism Institute.

Jaime Almandoz, MD, MBA, FTOS, DABOM, Professor at the University of Texas Southwestern Medical Center, addressed the added benefit of glucagon agonism in the context of existing GLP-1-based therapy.

“I think we know that there is substantial weight loss that can be achieved. There are reductions in adiposity, but also improvements in glycemic and liver biomarkers. We suspect that there will be liver health beyond weight. There may be impacts on energy expenditure, and there may be unique benefits to certain phenotypes,” Dr. Almandoz said. “What we need to know right now, and hopefully this will be coming soon, is what the cardiovascular outcomes are, what the outcomes on liver fibrosis are beyond non-invasive tests, and which patients will benefit most, and importantly, at what dose?”

Survodutide demonstrated a safety profile consistent with therapies that contain GLP-1 receptor agonist activity.

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Make plans to join us June 18–21, 2027, for the 2027 Scientific Sessions at the Walter E. Washington Convention Center in Washington, DC. Registration will open in January.