Boehringer's Survodutide Cuts Weight and Liver Fat in Two Phase 3 Trials at ADA

Boehringer Ingelheim presented full results from two Phase 3 trials of survodutide, its once-weekly glucagon/GLP-1 dual agonist, at the American Diabetes Association's 2026 Scientific Sessions in New Orleans on June 7, reporting weight loss of up to 16.6% in adults with obesity and liver fat reductions in adults with metabolic dysfunction-associated steatotic liver disease (MASLD). The results were described in the company's release, read via the PharmaShots newsroom, and in the ADA's own release. SYNCHRONIZE-1 was published in The New England Journal of Medicine and SYNCHRONIZE-MASLD in Nature Medicine.

Weight and fat loss in SYNCHRONIZE-1

The 76-week SYNCHRONIZE-1 trial enrolled adults with obesity or overweight who did not have type 2 diabetes. Boehringer had announced in April that it met its primary endpoints. Using the efficacy estimand, average weight loss reached up to 16.6% with survodutide, compared with 3.2% in the placebo arm (p<0.0001), the company said.

In a pre-specified MRI sub-study, survodutide reduced visceral fat by up to 34.0% from baseline and liver fat by up to 63.1%. Lean mass accounted for no more than 10.8% of the change in total tissue mass at the highest dose, which Boehringer said indicates the weight loss was driven mainly by loss of fat.

"There is a critical need for treatments that also drive meaningful improvements in overall metabolic health, and these findings are encouraging for potential new solutions," said Carel le Roux, lead author of the study, in the ADA release.

Liver results in SYNCHRONIZE-MASLD

The 48-week SYNCHRONIZE-MASLD trial enrolled adults with overweight or obesity and MASLD with evidence of inflammation or fibrosis, with and without type 2 diabetes. It met both co-primary endpoints, according to Boehringer: up to 84.2% of participants on survodutide achieved at least a 30% relative reduction in liver fat, against 24.3% on placebo, and body weight fell by up to 12.2%, against 1.0% on placebo (p<0.0001 for both).

In a secondary endpoint, up to 61.0% of survodutide-treated participants reached liver fat normalization, defined as liver fat content below 5%, at week 48, compared with 5.7% on placebo.

Tolerability and next steps

The most common adverse events in SYNCHRONIZE-1 were gastrointestinal, including nausea, vomiting, diarrhea and constipation, and were mostly mild to moderate and concentrated in the dose-escalation phase, the company said. Treatment discontinuation due to gastrointestinal adverse events was 19% with survodutide versus 2.9% with placebo. Boehringer said no new safety signals were identified in either trial, and that it would work on more optimized dosing guidance.

Survodutide is investigational and has not been approved for any use. Boehringer said it plans to start Phase IIIb studies later this year in women's health, cardiac function in MASLD or early MASH, and real-world titration, including switching from GLP-1 receptor agonists. The drug is also in two Phase 3 trials, LIVERAGE and LIVERAGE-Cirrhosis, in adults with MASH and fibrosis or compensated MASH cirrhosis.