Once-weekly survodutide safely tied to substantial weight loss in obese individuals: Study
Germany: In adults with a BMI of 27 kg/m2 or greater without diabetes, once-weekly survodutide produced significant reductions in body weight versus placebo from baseline to week 46, findings from a recent phase 2 trial have revealed. Survodutide's tolerability profile was in line with what would be expected based on its mechanism of action; participants most frequently reported gastrointestinal adverse events.
"All tested survodutide doses significantly reduced body weight in a dose-dependent manner relative to placebo in participants with a BMI of 27 kg/m2 or greater (0·6 mg, ≥2·4 mg)," the researchers reported in their study published in The Lancet Diabetes & Endocrinology.
Survodutide doses 2·4 mg or higher resulted in substantial, clinically relevant bodyweight losses of 5% or more in over half of the participants within 8 weeks of treatment initiation.
Obesity is a chronic and widespread condition that requires long-term management, research into additional targets to improve treatment outcomes remains a priority. Therefore, Anita M Hennige, Boehringer Ingelheim International GmbH, Biberach an der Riß, Germany, and colleagues aimed to investigate the efficacy, safety, and tolerability of glucagon receptor–GLP-1 receptor dual agonist survodutide (BI 456906) in obesity management.
For this purpose, the researchers conducted a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial in 43 centres in 12 countries. Participants aged 18–75 years, BMI ≥27 kg/m2, and without diabetes were enrolled. They were randomly assigned in a ratio of 1:1:1:1:1 to subcutaneous survodutide (0·6, 2·4, 3·6, or 4·8 mg) or placebo once-weekly for 46 weeks (20 weeks dose escalation; 26 weeks dose maintenance).
The study's primary endpoint was the percentage change in weight from baseline to week 46. The primary analysis included the modified intention-to-treat population and was based on the dose assigned at randomisation (planned treatment), containing all data censored for COVID-19-related discontinuation. The modified intention-to-treat population was defined as all randomly assigned patients who received at least one dose of trial medication and who had analysable data for at least one efficacy endpoint.
The sensitivity analysis was based on the actual dose received during the maintenance phase (actual treatment) and included on-treatment data. The safety analysis included all the participants who received at least one dose of the study drug.
387 participants were enrolled between March 30, 2021, and Nov 11, 2021; 386 participants were treated (0·6 mg, n=77; 2·4 mg, n=78; 3·6 mg, n=77; 4·8 mg, n=77; placebo n=77) and 233 of 386 completed the 46-week treatment period (187 of 309 receiving survodutide; 46 of 77 receiving placebo).
Based on the study, the researchers reported the following findings:
- When analysed according to planned treatment, mean changes in body weight from baseline to week 46 were −6·2%; −12·5%; −13·2%; −14·9%; −2·8%.
- Adverse events occurred in 91% of 309 survodutide recipients and 75% of 77 placebo recipients; these were primarily gastrointestinal in 75% of 309 survodutide recipients and 42% of 77 placebo recipients.
"All tested survodutide doses were tolerated, and dose-dependently reduced body weight," the researchers wrote. The effect of survodutide on body weight was sustained throughout the treatment period.
Reference:
Le Roux, C. W., Steen, O., Lucas, K. J., Startseva, E., Unseld, A., & Hennige, A. M. (2024). Glucagon and GLP-1 receptor dual agonist survodutide for obesity: A randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. The Lancet Diabetes & Endocrinology, 12(3), 162-173. https://doi.org/10.1016/S2213-8587(23)00356-X
