Dual Agonist Survodutide Delivers Up to 13.1% Weight Loss in T2D

Survodutide, an investigational glucagon/GLP-1 receptor dual agonist from Boehringer Ingelheim, led to average weight loss of up to 13.1% at 76 weeks in adults with obesity or overweight and type 2 diabetes (T2D), according to phase 3 SYNCHRONIZE-2 trial results. Participants receiving placebo lost 3.1% (P < .0001).^1-3

The findings were presented 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. The trial met both coprimary end points using the treatment-regimen and efficacy estimands.

SYNCHRONIZE-2 (NCT06066528) was a double-blind, placebo-controlled trial of 755 adults. Participants received weekly injections of survodutide at 3.6 mg or 6.0 mg, or placebo.⁴ The trial's 2 main goals were the percent change in body weight by week 76 and whether participants lost at least 5% of their baseline weight.

Up to 79.3% of adults treated with survodutide achieved a weight reduction of at least 5% compared with 32.7% on placebo (P < .0001), based on the efficacy estimand.^1-3

Glycemic Control and Cardiometabolic Markers

Survodutide also improved key secondary end points. Hemoglobin A_1C (HbA_1C) fell by up to 1.21% from a baseline of 7.4% compared with 0.03% with placebo (P < .0001). Waist circumference decreased by 11.1 cm vs 3.5 cm with placebo (P < .0001).

Compared with placebo, survodutide lowered fasting glucose and shifted measures of insulin resistance (homeostatic model assessment of insulin resistance) and insulin secretion (homeostatic model assessment of β-cell function) in a favorable direction. Up to 29.5% of those receiving survodutide reverted to normoglycemia (HbA_1C < 5.7%) vs 4.0% with placebo.

"Seeing improvements in glycemic control and insulin sensitivity alongside weight loss provides evidence that tackling obesity can positively influence broader metabolic health," trial investigator Sean Wharton, MD, PharmD, director of Wharton Medical Clinic, said in a statement.¹

Gastrointestinal (GI) events were the most commonly reported adverse events, and most were mild to moderate in severity. Nausea, vomiting, diarrhea, and constipation occurred more frequently with survodutide. Discontinuations due to GI adverse events reached 18% with survodutide vs 1.2% with placebo.^1-3

Treatment was stopped most often during the dose-escalation phase, which the trial protocol left little room to adjust for adverse effects. Boehringer Ingelheim said ongoing and planned studies build in more individualized titration to improve tolerability.¹

SYNCHRONIZE-1 Context and Body Composition Data

In SYNCHRONIZE-1 (NCT06066515), which enrolled adults without T2D, weight loss under the efficacy estimand reached 15.3% with 3.6 mg and 16.6% with 6.0 mg of survodutide vs 3.2% with placebo.⁵ GI events led to discontinuation in 17.8% and 20.2% of those groups, respectively, vs 2.9% with placebo.

Investigators also presented a body composition substudy of SYNCHRONIZE-1, which enrolled 75 adults with obesity without T2D. MRI scans found that visceral and liver fat were reduced to a greater degree than other tissue. A new muscle-specific analysis showed that no more than 10% of the tissue lost was muscle.⁶

The declines in visceral and liver fat did not appear to track closely with total weight lost, which suggests effects beyond weight reduction itself. Lee Kaplan, MD, PhD, chair of the SYNCHRONIZE program executive committee, has said that liver fat reductions in SYNCHRONIZE-1 appeared earlier than weight loss alone would explain.⁵

Next Steps for the Survodutide Program

Boehringer Ingelheim expects to present results from its cardiovascular outcomes trial, SYNCHRONIZE-CVOT (NCT06077864), later this year.^1,7 The company has also started the phase 3 SYNCHRONIZE-T2D trial (NCT07754461), which will test glycemic control in adults with T2D who use lifestyle measures alone or take diabetes drugs such as insulin.⁸

Survodutide is also being studied in phase 3 LIVERAGE trials (NCT06632444; NCT06632457) for metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis.^9,10 The FDA granted the agent Breakthrough Therapy designation for this indication in September 2024.¹¹ Survodutide remains investigational and is not approved for use, and its efficacy and safety have yet to be established.¹

References

1. Boehringer Ingelheim's survodutide achieves up to 13.1% weight loss in new phase III trial, alongside significant improvements in glycemic control in people with obesity and type 2 diabetes. News release. Boehringer Ingelheim; October 1, 2026. Accessed October 1, 2026.
2. Wharton S. Efficacy and safety of survodutide, a novel GCG/GLP-1 receptor dual agonist, for treatment of people with obesity and T2D: primary data from the SYNCHRONIZE-2 trial. Presented at: 62nd Annual Meeting of the European Association for the Study of Diabetes; October 1, 2026; Milan, Italy.
3. Wharton S, et al. Survodutide once weekly in adults with obesity and type 2 diabetes. N Engl J Med. Published online October 1, 2026. doi:10.1056/NEJMoa2607219
4. A study to test whether survodutide (BI 456906) helps people living with overweight or obesity who also have diabetes to lose weight (SYNCHRONIZE-2). ClinicalTrials.gov. Updated August 6, 2026. Accessed September 30, 2026. https://clinicaltrials.gov/study/NCT06066528
5. Shaw ML. Survodutide phase 3 data signal metabolic gains beyond weight loss. AJMC^®. June 8, 2026. Accessed September 30, 2026. https://www.ajmc.com/view/survodutide-phase-3-data-signal-metabolic-gains-beyond-weight-loss
6. Pietiläinen K. Metabolic benefits of glucagon receptor/GLP-1 receptor dual agonism beyond weight reduction: additional insights from the SYNCHRONIZE-1 phase 3 clinical trial. Presented at: 62nd Annual Meeting of the European Association for the Study of Diabetes; October 1, 2026; Milan, Italy.
7. A study to test the effect of survodutide (BI 456906) on cardiovascular safety in people with overweight or obesity (SYNCHRONIZE-CVOT). ClinicalTrials.gov. Updated September 30, 2026. Accessed September 30, 2026. https://clinicaltrials.gov/study/NCT06077864
8. A study to test whether survodutide helps people with type 2 diabetes control their blood sugar. ClinicalTrials.gov. Updated September 30, 2026. Accessed September 30, 2026. https://clinicaltrials.gov/study/NCT07754461
9. LIVERAGE: a study to test whether survodutide helps people with a liver disease called NASH/MASH who have moderate or advanced liver fibrosis. ClinicalTrials.gov. Updated September 17, 2026. Accessed September 30, 2026. https://clinicaltrials.gov/study/NCT06632444
10. LIVERAGE-Cirrhosis: a study to test whether survodutide helps people with a liver disease called NASH/MASH who have cirrhosis. ClinicalTrials.gov. Updated September 18, 2026. Accessed September 30, 2026. https://clinicaltrials.gov/study/NCT06632457
11. Boehringer receives U.S. FDA Breakthrough Therapy designation and initiates two phase III trials in MASH for survodutide. News release. Boehringer Ingelheim. August 10, 2024. Accessed September 30, 2026. https://www.boehringer-ingelheim.com/human-health/metabolic-diseases/survodutide-us-fda-breakthrough-therapy-phase-3-trials-mash