Patients With Overweight or Obesity Show Significant Weight Loss in Phase 2 Survodutide Trial

Survodutide (BI 456906) has demonstrated promising results in a phase 2 trial for individuals without type 2 diabetes who have overweight or obesity, according to a press release from Boehringer Ingelheim.¹

Survodutide is a glucagon/GLP-1 receptor dual agonist that activates the glucagon and GLP-1 receptors, both of which are critical in controlling metabolic functions. The drug was developed by Boehringer Ingelheim and Zealand Pharma, and the trial data was presented at the American Diabetes Association (ADA) 83rd Scientific Sessions.

According to the study, survodutide led to a weight loss of nearly 19% in participants who received the 4.8 mg dose weekly for 46 weeks.²

“Given the prevalence of obesity and its many disease-related complications, there is a dire need for treatments that can help treat the disease of obesity effectively,” said Carel le Roux, MD, PhD, professor at University College in Dublin, Ireland, and principal investigator of the trial. “Current treatments for obesity mainly focus on weight loss by reducing energy intake. By activating both the glucagon and GLP-1 receptors, survodutide may both inhibit appetite and improve energy expenditure, thereby helping to treat the disease of obesity. These encouraging data support the further study of survodutide in larger Phase III trials.”

The double-blind, placebo-controlled study included 387 adult patients—only 3 of whom did not complete the full study—who were randomized to receive placebo or 0.6, 2.4, 3.6, or 4.8 mg of survodutide subcutaneously, with 77 participants in each arm. The trial consisted of a 20-week rapid, biweekly dose escalation phase followed by a 26-week maintenance phase.

All participants had a body mass index (BMI) of at least 27 kg/m2 at the start of the trial, and weight loss was tracked by body weight rather than BMI. At baseline, the mean age was 49.1 years, the mean body weight was 105.7 kg or 233 lbs, and the mean BMI was 37.1 kg/m2.

Mean body weight reductions among patients were greater as the dosage increased, as mentioned in an ADA press release.³ The mean reduction was -6.2% for the 0.6 mg dose, -12.5% for the 2.4 mg dose, -13.2% for the 3.6 mg dose, and -14.9% for the 4.8 mg dose. Meanwhile, the researchers saw a -2.8% mean body weight reduction in the placebo group.

After 46 weeks of treatment, individuals who reached and maintained the 4.8 mg dose of survodutide achieved a weight loss of 18.7%. The trial also showed that 82.8% of participants in the 4.8 mg dosage group achieved a weight reduction of at least 5% by week 46, compared with only 25.9% in the placebo group.

Additionally, of those receiving 4.8 mg of the drug, 68.8% achieved weight loss of 10% or more, and 54.7% achieved weight loss of 15% or more. Among participants who received the 2 highest doses, up to 40% achieved weight loss of 20% or more, while none of the participants in the placebo group hit this mark.

The study results also indicate that the weight loss benefits of survodutide continued to increase even after 46 weeks of treatment, highlighting the potential for additional weight loss with longer treatment durations.

Regarding safety and tolerability, survodutide did not raise any unexpected concerns, according to the Boehringer Ingelheim press release. Serious adverse events were reported by 4.2% of participants receiving survodutide, compared with 6.5% in the placebo group. Gastrointestinal adverse events were the main cause of treatment discontinuation, which was higher in the survodutide group (24.6%) compared with the placebo group (3.9%). Finally, most discontinuations occurred during the rapid dose-escalation phase and may be mitigated by implementing a more gradual dose escalation. The researchers also noted that the reported adverse events were consistent with those typically associated with the GLP1-R agonist class of drugs.

According to the ADA press release, these findings come at a time where more than 37 million Americans have diabetes, more than 100 million have obesity, nearly 90% of Americans with diabetes have overweight or obesity, and an estimated half of all Americans will have obesity by 2030. Despite these important statistics, existing treatments for obesity are limited in their effectiveness.

“Addressing the twin epidemics of obesity and diabetes is critical to slowing the trajectory of this ongoing public health crisis,” said Robert Gabbay, MD, PhD, FACP, chief scientific and medical officer for the ADA. “We have seen an explosion of promising new research and innovations in this field in recent years. The studies presented at this year’s annual meeting are game-changers in the way we customize treatment for individuals with obesity and those with type 2 diabetes.”

References

1. Data shows nearly 19% weight loss in people with overweight or obesity in Boehringer Ingelheim and Zealand Pharma Phase II trial with survodutide (BI 456906). News release. Boehringer Ingelheim. June 23, 2023. Accessed July 10, 2023. https://www.boehringer-ingelheim.com/human-health/metabolic-diseases/obesity/phase-ii-clinical-trial-weight-loss-results
2. Le Roux C, Steen O, Lucas KJ, Startseva E, Unseld A, Hennige AM. 51-OR: A phase 2, randomized, double-blind, placebo-controlled, dose-finding study of BI 456906 in people with overweight/obesity. Diabetes. 2023;72(suppl 1):51-OR. doi:10.2337/db23-51-OR
3. Late Breaking Weight Loss Innovations: New Drug Therapies Shown to Offer Positive Outcomes for Obesity and Type 2 Diabetes Management. News release. American Diabetes Association. June 25, 2023. Access July 10, 2023. https://diabetes.org/newsroom/press-releases/2023/late-breaking-weight-loss-innovations-new-drug-therapies-shown-offer-positive-outcomes-obesity-type-2-diabetes-management