Survodutide substantially reduces weight and liver fat in adults with obesity, phase 3 SYNCHRONIZE studies show
Presenters: Carel le Roux, MD, PhD, University College Dublin School of Medicine, Dublin, Ireland
Lee M. Kaplan, MD, PhD, The Obesity and Metabolism Institute, Boston, MA, and Geisel School of Medicine at Dartmouth, Hanover, NH
The Benefits of Glucagon/GLP-1 Receptor Dual Agonism: Insights from the SYNCHRONIZE Phase 3 Studies of Survodutide. Presented June 7, 2026.
Survodutide, an investigational once-weekly dual glucagon/glucagon-like peptide-1 (GLP-1) receptor agonist, led to substantial weight loss in adults with obesity, and it reduced liver fat in adults with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), according to two phase-3 trials presented at the American Diabetes Association 2026 Scientific Sessions.
In SYNCHRONIZE-1, adults with obesity without diabetes lost about 13% of their body weight over 76 weeks on the higher of two doses evaluated. In SYNCHRONIZE-MASLD, most adults with obesity and serious fatty liver disease reached at least a 30% reduction in liver fat over 48 weeks.
A pressing need remains for therapies that improve overall metabolic health, not just weight alone, and as such, these treatment results are encouraging, according to Carel le Roux, MD, PhD, lead author of SYNCHRONIZE-1.
“For patients, improving metabolic health is about more than weight loss alone—it can help reduce the risk of serious complications linked to obesity, including cardiovascular disease, type 2 diabetes, and liver-related conditions, while supporting better long-term health outcomes and quality of life,” Dr. le Roux said.
Medications that target the GLP-1 receptor have markedly advanced obesity treatment, but responses to current medications are heterogeneous, according to the study authors. “Compounds with complementary mechanisms that may expand treatment options for managing the disease, addressing metabolic dysfunction beyond weight loss, and ameliorating complications would be useful,” Dr. le Roux and co-authors wrote in a report on the study published simultaneously in The New England Journal of Medicine.
Obesity is a chronic metabolic disease that affects roughly 75% of adults with obesity, about a third of whom have the progressive form, known as metabolic dysfunction-associated steatohepatitis (MASH), the SYNCHRONIZE-MASLD authors noted in their report. Left untreated, MASH can lead to liver fibrosis and cirrhosis, raising the likelihood of serious liver complications, they added.
SYNCHRONIZE-1
SYNCHRONIZE-1 (NCT06066515) was a 76-week, randomized, double-blind, placebo-controlled phase 3 trial conducted at 116 sites in 14 countries. It enrolled 725 adults with obesity and without diabetes; obesity was defined as a body mass index of 30 kg/m2 or higher, or 27 kg/m2 or higher with at least 1 obesity-related complication (excluding diabetes).
Participants were randomly assigned in a 1:1:1 ratio to receive once-weekly subcutaneous injections of survodutide 3.6 mg, survodutide 6.0 mg, or placebo, alongside counseling on diet and physical activity. The primary endpoints were the percent change in body weight and a reduction in body weight of at least 5%, both from baseline to week 76.
In the primary analysis, mean body weight fell 13.0% with survodutide 6.0 mg (95% confidence interval –14.4 to –11.6) and 12.2% with 3.6 mg, compared with 5.4% with placebo. By the efficacy estimand, mean weight loss reached 16.6% with the 6.0-mg dose.
A reduction of at least 5% was reached by 72.6% and 71.9% of the survodutide groups, respectively, versus 46.3% with placebo (P < .001 for both comparisons). In a prespecified MRI substudy of 25 participants per group, the 6.0-mg dose reduced visceral fat by 34.0% and liver fat by 63.1%, compared with 11.8% and 24.5% with placebo.
Gastrointestinal symptoms, mostly mild to moderate, were the most common adverse events, and no deaths were reported.
SYNCHRONIZE-MASLD
SYNCHRONIZE-MASLD (NCT06309992) was a 48-week, randomized, double-blind, placebo-controlled phase 3 trial in 216 adults with obesity and at-risk MASLD, defined by liver inflammation or fibrosis on noninvasive tests or recent biopsy-confirmed MASH. Participants were randomized in a 2:1 ratio to receive once-weekly subcutaneous injections of survodutide titrated to 6.0 mg (146 participants) or placebo (70 participants).
The primary endpoints were a reduction of at least 30% in liver fat content measured by MRI and the percent change in body weight, both from baseline to week 48.
Analysis showed that 84.2% of survodutide-treated participants achieved at least a 30% reduction in liver fat, versus 24.3% with placebo (P < .0001). Mean body weight fell 12.2% with survodutide versus 1.0% with placebo (P < .0001).
Survodutide also lowered markers of liver inflammation, waist circumference, blood pressure, and lipids, and no cases of drug-induced liver injury were adjudicated, the authors reported. As in SYNCHRONIZE-1, gastrointestinal events were the most frequent adverse effects and occurred mainly during dose escalation.
Although neither trial was designed as a cardiovascular outcomes trial, the SYNCHRONIZE-MASLD authors characterized the combined metabolic gains as a potential long-term advantage of treating early. “Effective treatment of MASLD early in the disease course along with improvement in cardiometabolic parameters may prevent progression of cardiovascular disease and reduce the risk of future cardiac events,” Dr. Kaplan and co-authors wrote.
Further survodutide trials are underway, including studies in more advanced liver disease and a cardiovascular outcomes trial, they noted.
Disclosures
Both trials were sponsored, designed, and funded by Boehringer Ingelheim. Author disclosures for SYNCHRONIZE-MASLD included Boehringer Ingelheim, among others. Author disclosures for SYNCHRONIZE-1 were provided alongside the full text article at NEJM.org.
References
le Roux CW, Wharton S, Startseva E, et al; SYNCHRONIZE-1 Investigators. Survodutide once weekly for the treatment of adults with obesity. N Engl J Med 2026 Jun 7. doi:10.1056/NEJMoa2600751.
Kaplan LM, Startseva E, le Roux CW, et al; SYNCHRONIZE-MASLD Investigators. Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med 2026 Jun 7. doi:10.1038/s41591-026-04479-3
American Diabetes Association. Once-weekly drug demonstrates promising dual benefits in obesity and metabolic health [press release]. New Orleans, LA: ADA; June 7, 2026.