Treatment with the investigational glucagon/GLP-1 receptor dual agonist (RA) survodutide results in significant weight reductions in adults with obesity and type 2 diabetes (T2D), a study has shown.
“Survodutide … facilitated sustained body weight reductions of up to 13.1 percent in people with obesity and T2D [and] meaningful improvements in glycaemic control,” said lead study author Dr Sean Wharton, University of Toronto, Toronto, Canada, who presented the finding at EASD 2026.
A total of 755 participants were included in the trial, of whom three did not meet the eligibility criteria and were excluded from the modified intention-to-treat population. The remaining 752 adults with obesity and T2D (mean age at baseline 55.7 years, mean BMI 36.5 kg/m2, 50.7 percent women) received either once-weekly survodutide (3.6 [n=250] or 6.0 mg [n=251]) or placebo [n=251].
Weight loss
At week 76, the mean change in body weight according to the efficacy estimand was ‒13.1 percent in the 6.0-mg survodutide group and ‒10.4 percent in the 3.6-mg group compared with ‒3.1 percent in the placebo group. [N Engl J Med 2026;doi:10.1056/NEJMoa2607219]
In the treatment-regimen estimand (which assessed effects regardless of whether the regimen was discontinued or other antiobesity drugs were used), the mean body weight change at week 76 was ‒9.8 percent (95 percent confidence interval [CI], ‒10.8 to ‒8.8) and ‒8.2 percent (95 percent CI, ‒9.2 to ‒7.2) with survodutide 6.0 and 3.6 mg, respectively, vs ‒3.9 percent (95 percent CI, ‒4.9 to ‒2.9) with placebo.
Weight reduction of at least 5 percent occurred in 64.5 percent and 57.6 percent of participants in the survodutide 6.0- and 3.6-mg groups compared with 35.1 percent of those on placebo (p<0.001 for all comparisons with placebo).
“Survodutide offers a dual mechanism for treating obesity and other diseases such as metabolic dysfunction–associated steatohepatitis, which potentially affects approximately one third of persons with T2D,” Wharton and colleagues wrote. [J Hepatol 2019;71:793-801]
GLP-1 receptor agonism reduces body weight primarily by decreasing energy intake, whereas glucagon receptor agonism also reduces energy intake and has lipolytic effects in the liver,” they added. [Mol Metab 2022;57:101351-101351; Int J Obes (Lond) 2022;46:1948-1959; Front Physiol 2019;10:413-413]
Glycaemic control
From a baseline level of 7.4 percent, the mean change in glycated haemoglobin level based on the treatment-regimen estimand was ‒0.8 percentage points in the survodutide 6.0-mg group, ‒0.9 percentage points in the 3.6-mg group, and ‒0.2 percentage points in the placebo group. Differences from placebo were ‒0.6 and ‒0.7 percentage points with the 6.0- and 3.6-mg dose groups, respectively.
According to the efficacy estimand, differences from placebo were ‒1.1 percentage points with 6.0 mg and ‒1.2 percentage points with 3.6 mg.
Furthermore, the mean change in the high-sensitivity C-reactive protein level from baseline to week 76 was ‒53.4 percent with survodutide 6.0 mg, ‒50.2 percent with 3.6 mg, and ‒17.0 percent with placebo.
“These results are encouraging because, in obesity medicine, clinicians increasingly recognize the opportunity to address multiple interconnected health conditions together,” Wharton said. [https://www.boehringer-ingelheim.com/human-health/crm-health/metabolic-health/survodutide-synchronize-2-phase-3-obesity-type-2-diabetes-results]
“Seeing improvements in glycaemic control and insulin sensitivity alongside weight loss provides evidence that tackling obesity can positively influence broader metabolic health,” he added.
In terms of safety, the most common adverse events (AEs) were gastrointestinal (mild-to-moderate intensity and transient), occurring in 195 participants (77.7 percent) in the 6.0-mg group, 182 (72.8 percent) in the 3.6-mg group, and 97 (38.6 percent) in the placebo group. Serious AEs of any kind occurred in 8.4 percent, 9.2 percent, and 10.8 percent of participants, respectively.
“Survodutide demonstrated a safety profile consistent with therapies with GLP-1 RA activity, with no additional safety findings attributable to the inclusion of glucagon receptor agonism,” Wharton said.