Survodutide shows notable weight reduction in people with type 2 diabetes and obesity

Key takeaways:

• Among adults treated with survodutide 6 mg, 64.5% achieved at least 5% body weight loss over 76 weeks.
• Both survodutide 3.6 mg and 6 mg lowered HbA1c more than placebo at 76 weeks.

A once-weekly GLP-1/glucagon dual agonist produced body weight reductions of as much as 9.8% at 76 weeks in adults with type 2 diabetes and overweight or obesity, according to results from the SYNCHRONIZE-2 trial.

Earlier findings had shown that survodutide, an injectable therapy developed by Boehringer Ingelheim and Zealand Pharma, led to weight loss of up to 13% in adults with overweight or obesity without diabetes in the SYNCHRONIZE-1 trial. New data from the phase 3 SYNCHRONIZE-2 study, presented at the European Association for the Study of Diabetes annual meeting and published at the same time in The New England Journal of Medicine, indicate that the drug also produced meaningful weight loss in adults who had both excess weight and type 2 diabetes.

Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic and assistant professor at the University of Toronto, said the amount of weight loss seen with survodutide was especially notable.

“It was an impressive amount of weight loss in patients living with type 2 diabetes,” Wharton told Healio. “Patients with type 2 diabetes tend to not lose as much weight as those without type 2 diabetes, so to see a 13.1% weight loss in patients with type 2 diabetes over this timeframe is impressive.”

SYNCHRONIZE-2 enrolled 752 adults with type 2 diabetes and a BMI of at least 27 kg/m² (mean age, 55.7 years; 49.3% men). Participants were randomly assigned to receive once-weekly subcutaneous survodutide at 3.6 mg or 6 mg, or placebo. The two primary endpoints were change in body weight from baseline to 76 weeks and the proportion of adults who lost at least 5% of their body weight at 76 weeks.

Study outcomes

Using the treatment-regimen estimand, adults in the 3.6 mg survodutide group lost 8.2% of body weight at 76 weeks, while those receiving 6 mg lost 9.8%, compared with a 3.9% loss in the placebo group (P < .001 for both). Under the efficacy estimand, weight change from baseline to 76 weeks was –10.4% with survodutide 3.6 mg and –13.1% with survodutide 6 mg, versus –3.1% with placebo.

The share of adults losing at least 5% of body weight was 57.6% with survodutide 3.6 mg, 64.5% with survodutide 6 mg and 35.1% with placebo (P < .001 for both).

From baseline to 76 weeks, HbA1c fell by 0.9 percentage points in the 3.6 mg group and by 0.8 percentage points in the 6 mg group, compared with a 0.2-point decrease with placebo (P < .001).

Mean reductions in high-sensitivity C-reactive protein at 76 weeks were 50.2% with survodutide 3.6 mg and 53.4% with survodutide 6 mg, compared with 17% with placebo.

Safety data

Gastrointestinal adverse events were reported in 72.8% of participants receiving survodutide 3.6 mg, 77.7% of those receiving 6 mg and 38.6% of those given placebo. Most events were mild to moderate. Gastrointestinal adverse events led to treatment discontinuation in 18% of the 3.6 mg group and 17.9% of the 6 mg group, compared with 1.2% of the placebo group.

“The good news is [the safety profile] was similar to what we see with other GLP-1 receptor agonists in the sense that the most common were the gastrointestinal side effects: nausea, vomiting, constipation [and diarrhea],” Wharton said.

Serious adverse events occurred in 9.2% of the 3.6 mg group, 8.4% of the 6 mg group and 10.8% of adults receiving placebo. One case of level 3 hypoglycemia occurred in a participant taking survodutide 3.6 mg. One case of acute pancreatitis was reported in the placebo group. Two major adverse cardiovascular events occurred during the trial, both in the survodutide 3.6 mg group.

A potential role

Wharton said survodutide may fill an important gap in type 2 diabetes treatment, especially for people at risk for metabolic dysfunction-associated steatotic liver disease. In the SYNCHRONIZE-MASLD trial presented at the American Diabetes Association Scientific Sessions, 84.2% of adults with overweight or obesity at risk for metabolic dysfunction-associated steatotic liver disease who received survodutide had a reduction of at least 30% in liver fat content.

He added that the glucagon component of survodutide appears to act on the liver, which could give the drug added advantages over other dual-receptor agonists.

“If you have a type 2 diabetes drug that also can take care of liver pathology and liver health, that would be a very positive thing,” Wharton said. “You would be addressing two problems, and the likelihood that a patient with type 2 diabetes and elevated weight ... will also have MASLD or some degree of metabolic dysfunction-associated steatohepatitis is high. That's why I see this as armamentarium in the type 2 diabetes world.”

For more information:

Sean Wharton, MD, PharmD, can be reached at sean@whartonmedicalclinic.com.