SYNCHRONIZE-2: Survodutide Outperforms Placebo in Weight Loss, Blood Sugar Control

Survodutide, a combination glucagon/GLP-1 receptor dual agonist, has significantly outperformed placebo in the SYNCHRONIZE-2 trial.1

Announced by parent company Boehringer Ingelheim, survodutide resulted in comparatively greater weight loss among patients with obesity and type 2 diabetes (T2D) compared to placebo. Additionally, the investigational treatment largely removed fat from the liver, targeting another key factor of obesity and T2D complications.1

“There are a lot of other molecules that are being investigated, but what we have here is a unique combination of GLP-1 and glucagon – I think that what we’re looking at is health overall,” Sean Wharton, MD, PharmD, medical director of Wharton Medical Center and coordinating investigator of SYNCHRONIZE-2, told HCPLive in an exclusive interview. “I think we’re entering into the realm where GLP-1s need to be combined with specific agents that do specific things to get us not only weight loss, but also other health parameters with a more guaranteed benefit.”

SYNCHRONIZE-2 was a phase 3, randomized, double-blind, parallel-group efficacy and safety study that lasted 76 weeks and was conducted across 143 locations worldwide. Patients were eligible for inclusion if they had a body mass index (BMI) ≥27 kg/m2 at screening, a diagnosis of T2D mellitus, HbA1c ≥6.5% and <10%, and ≥1 self-reported unsuccessful dietary effort to lose weight. Patients with weight changes >5% within 3 months prior to screening, treatment with obesity medication within 3 months, or a clinically significant gastric emptying abnormality, among other criteria, were excluded.2

Enrolled patients were randomly assigned to receive either survodutide in a 3.6 mg or 6 mg dose once weekly or placebo, all of which were administered via subcutaneous injection. The primary outcomes of the study were percentage change in body weight from baseline and achievement of body weight reduction ≥5% from baseline. Secondary outcomes included body weight reduction ≥10%, ≥15%, and ≥20% from baseline, as well as absolute change in body weight, glycosylated HbA1c, and others.2

A total of 752 patients were enrolled in the trial. These patients had a mean age of 55.7 years and a mean overall BMI of 36.5 kg/m2 at baseline. Additionally, mean body weight was 229.5 lb and mean waist circumference was 45.5 in. Mean HbA1c at baseline was 7.4% (57.4 mmol/mol). Metformin was the most commonly taken medication (78.7%), followed by lipid-lowering therapies (58.6%) and SGLT2 inhibitors (34.2%).3

By week 76, Wharton and colleagues noted an average sustained weight loss ≤13.1% in the survodutide arm, compared to 3.1% in the placebo arm (P <.0001). Additionally, ≤79.3% of survodutide recipients achieved a body weight reduction ≥5%, using the efficacy estimand, while the placebo arm only saw 32.7% meet the same endpoint (P <.0001). Survodutide also led to substantial improvements in blood sugar control, with patients experiencing a reduction of ≤1.21% in HbA1c versus 0.03% in the placebo arm (P <.0001).1

Taken in conjunction with data from the prior SYNCHRONIZE-1 trial, Wharton and colleagues determined that, in addition to substantial weight loss and blood sugar control improvements, survodutide has an additional effect on the liver. A muscle-specific analysis of the previous trial demonstrated that treatment caused preferential reductions in metabolically active visceral and liver fat, as opposed to lean mass. Ultimately, the team determined that this secondary effect is what truly positions survodutide as its own unique treatment beyond traditional GLP-1 therapies.1

“I feel that this is a molecule that’s going to do weight change, but I also feel that it has a liver health aspect to it. And more and more, we’re going to start to see that, for people with type 2 diabetes, the liver is important,” Wharton said. “I think we’re starting on a path towards really positive health.”

Editors’ Note: Wharton reports disclosures with Novo Nordisk, Eli Lilly, BI, and Bausch Health Canada.

References

1. Boehringer Ingelheim. 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. October 1, 2026. Accessed October 1, 2026. https://www.boehringer-ingelheim.com/human-health/crm-health/metabolic-health/survodutide-synchronize-2-phase-3-obesity-type-2-diabetes-results

2. Boehringer Ingelheim. 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 Identifier: NCT06066528. Updated August 6, 2026. Accessed October 1, 2026. https://clinicaltrials.gov/study/NCT06066528

3. Wharton S, le Roux CW, Bozkurt B, et al. Baseline characteristics in the SYNCHRONIZE™-2 randomized phase 3 trial of survodutide, a glucagon receptor/GLP-1 receptor dual agonist, for obesity in people with type 2 diabetes. Diabetes Obes Metab. 2026;28(2):1490-1498. doi:10.1111/dom.70263