Survodutide Targets Obesity, Diabetes: Sean Wharton, MD, PharmD

Survodutide (Boehringer Ingelheim), a dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist, may offer the greatest benefit to patients living with obesity and type 2 diabetes (T2D), particularly those who also have fatty liver disease, according to Sean Wharton, MD, PharmD, director of Wharton Medical Clinic, and SYNCHRONIZE trial investigator.

Data from the SYNCHRONIZE-2 (NCT06066528) trial were presented today at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) and simultaneously published in The New England Journal of Medicine.¹ The trial met both coprimary end points using the treatment-regimen and efficacy estimands.

Glucagon alone can raise blood sugar, Wharton said in an interview with The American Journal of Managed Care^®, but combined with GLP-1 activity, the agent lowered glucose significantly in the trial. Baseline Hemoglobin A_1C (HbA_1C) may determine how many agents patients need. Those starting near 7.0% to 7.5% may reach target with survodutide alone, he said, while patients with much higher values likely need additional therapy. An A_1C below 6% would be an excellent result. Insulin was an exclusion criterion, so how survodutide performs alongside insulin remains unknown.

Titration Limited Tolerability Data

Wharton called the rigid titration schedule one of the study's most important features. The protocol allowed no flexibility during the first 16 weeks, modest flexibility from weeks 16 to 32, and less afterward. Patients who could not tolerate the drug early withdrew, which reduced the number available for analysis. A more flexible schedule might improve tolerability and retention, he said.

He also emphasized that the molecule promotes fat oxidation in the liver, as seen in SYNCHRONIZE-1 (NCT06066515). Some patients had substantial liver fat loss despite modest weight loss, suggesting weight loss-independent mechanisms, possibly driven by the glucagon component alongside weight change.

Cardiometabolic Markers Improved

Across the SYNCHRONIZE trials, including SYNCHRONIZE-1 and SYNCHRONIZE-2, waist circumference, systolic blood pressure, lipids, and high-sensitivity C-reactive protein (hs-CRP) improved. The hs-CRP level fell by more than 50% in SYNCHRONIZE-2, which Wharton said suggests less inflammation in the heart, coronary arteries, and kidneys and may point to benefit in the cardiovascular safety trial, SYNCHRONIZE-CVOT (NCT06077864).

Reference

1. Grossi G. Dual agonist survodutide delivers up to 13.1% weight loss in T2D. AJMC^®. October 1, 2026. Accessed October 1, 2026. https://www.ajmc.com/view/dual-agonist-survodutide-delivers-up-to-13-1-weight-loss-in-t2d