Survodutide reduces weight and steatosis in patients with overweight/obesity and at-risk MASLD

ADA 2026 – In SYNCHRONIZE-MASLD, survodutide lowered body weight and liver fat content at 48 weeks compared with placebo in patients with overweight or obesity and metabolic dysfunction–associated steatotic liver disease (MASLD) with evidence of inflammation and/or fibrosis.

This summary is based on the presentation of Lee Kaplan, MD, PhD (Boston, MA, USA) at the ADA Scientific Sessions 2026 - Design and Outcomes of SYNCHRONIZE-MASLD: Survodutide for the Treatment of Obesity and MASLD.

Introduction and methods

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a common and heterogenous chronic liver disease. The progressive form of MASLD, metabolic dysfunction–associated steatohepatitis (MASH), is characterized by hepatic steatosis, inflammation, and hepatic cell injury. Survodutide, a dual glucagon/GLP-1 receptor agonist, ameliorated MASH and liver fibrosis and reduced body weight compared with placebo, as shown by several phase 2 trials.

The efficacy and safety of survodutide were further investigated in the SYNCHRONIZE-MASLD trial, a multicenter, double-blind, placebo-controlled, phase 3 RCT conducted in the USA (31 sites) and Spain (1 site). In total, 218 patients with BMI ≥30 kg/m² or ≥27 kg/m² with ≥1 obesity-related complication who had at-risk MASLD, defined as MASLD with either evidence of liver inflammation and/or fibrosis or biopsy-confirmed MASH, were included. Both patients with and with no T2D were eligible. Participants were randomized in a 2:1 ratio to subcutaneous survodutide 6 mg or placebo once weekly for 48 weeks (including a dose-escalation period of 24 weeks).

The coprimary endpoints were the percentage change in body weight and achievement of a reduction in liver fat content (LFC) ≥30% as assessed with MRI proton density fat fraction (MRI-PDFF), both measured from baseline to 48 weeks. Secondary endpoints included absolute and relative changes in waist circumference, MRI-PDFF LFC, ALT levels, and homeostatic model assessment of insulin resistance (HOMA-IR). Additional prespecified endpoints included changes in blood pressure and HbA1c and lipid levels.

Main results

• Among the participants who received ≥1 dose of the study drug (n=216), the mean relative change in body weight from baseline to 48 weeks was −8.7% in patients treated with survodutide (n=146) and −1.4% in patients receiving placebo (n=70) (estimated treatment difference (ETD): −7.3%; 95%CI: −9.4% to −5.2%; P<0.0001).
• In addition, 68.5% of the survodutide-treated patients achieved a reduction in MRI-PDFF–assessed LFC ≥30% at 48 weeks, compared with 28.6% of the placebo-treated patients (OR: 5.9; 95%CI: 2.9–11.9; P<0.0001).
• The secondary and additional endpoints were analyzed in per-protocol analyses. From baseline to 48 weeks, the mean waist circumference was reduced by 11.1 cm in the survodutide group and by 1.9 cm in the placebo group (ETD: 9.3 cm, 95%CI: −11.8 to −6.8).
• Survodutide versus placebo treatment was also associated with larger absolute reductions in systolic blood pressure (ETD: –7.4 mmHg), diastolic blood pressure (ETD: –2.7 mmHg), and HbA1c (ETD: –0.6%), as well as greater relative reductions in the levels of HOMA-IR (ETD: –38.7%), total cholesterol (ETD: –8.9%), triglycerides (ETD: –30.8%), and hs-CRP (ETD: –42.1%).
• The incidence of adverse events was 87.0% in the survodutide group and 78.6% in the placebo group.
• The most common reported adverse were gastrointestinal disorders (typically mild to moderately severe), which occurred in 19.9% of the survodutide-treated patients and 4.3% of the placebo-treated patients.
• There was 1 death reported in the placebo group and none in the survodutide group.

Conclusion

The SYNCHRONIZE-MASLD trial demonstrated that treatment with survodutide 6 mg reduced body weight and MRI-PDFF–assessed LFC at 48 weeks compared with placebo in patients with overweight or obesity and at-risk MASLD. In addition, survodutide treatment was associated with improved cardiometabolic parameters compared with placebo. The safety profile of survodutide was consistent with that of GLP-1RAs. Prof. Kaplan remarked that survodutide is now being investigated for biopsy-confirmed MASH with moderate-to-advanced fibrosis (LIVERAGE trial) and MASH with compensated cirrhosis (LIVERAGE-Cirrhosis trial).

- Our reporting is based on the information provided at the ADA Scientific Sessions 2026 and publication of the data in Nature Medicine -

The findings of this study were simultaneously published in Nat Med.