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01-03-2024 | Obesity | News

Survodutide induces weight loss in phase 2 obesity trial

Author: Sara Freeman

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medwireNews: Survodutide, a dual agonist of glucagon-like peptide (GLP)-1 and glucagon receptors, dose-dependently reduces bodyweight in people without diabetes who have a BMI of 27 kg/m² or greater, according to the results of a randomized, double-blind, phase 2 trial.

In a planned treatment analysis, baseline bodyweight was reduced by 14.9% after 46 weeks of treatment with the highest (4.8 mg) once-weekly subcutaneous dose of survodutide that was tested (n=76). And by a respective 13.2%, 12.5%, and 6.2% for doses of 3.6 mg (n=76), 2.4 mg (n=78), and 0.6 mg (n=77). Meanwhile, individuals treated with placebo (n=77) lost just 2.8% of their baseline bodyweight.

“Mean reductions in bodyweight were approximately 5 times greater for participants receiving survodutide 4.8 mg versus placebo,” write Anita Hennige (Boehringer Ingelheim International GmbH, Biberach, Germany) and fellow investigators in The Lancet Diabetes & Endocrinology.

When they did an analysis based on participants who had actually received a dose of the allocated medication, they found that the weight loss reductions were higher, at 18.7%, 16.7%, 13.6%, and 6.8% for survodutide at doses of 4.8 mg, 3.6 mg, 2.4 mg, and 0.6 mg versus 2.3% for placebo.

Moreover, the researchers report that 81.0% to 82.8% of participants treated with the three highest doses of survodutide achieved clinically relevant bodyweight losses of 5% or more within 8 weeks of treatment initiation, compared with 25.9% of those given placebo. And the effects on bodyweight were sustained throughout the treatment period.

“Survodutide appears to be a promising new anti-obesity treatment and warrants further investigation in phase 3 trials,” Hennige et al suggest.

They acknowledge that while more patients treated with survodutide than placebo experienced adverse events (91 vs 75%), most of which were gastrointestinal, the “tolerability profile of survodutide was in line with what would be expected based on its mechanism of action.”

Serious adverse events of nausea, vomiting, dehydration, and renal failure occurred in one participant who had been treated with survodutide 0.6 mg, and angioedema was reported in one individual treated with survodutide 3.6 mg. 

The rate of discontinuation due to adverse events was 25% in the survodutide-treated patients versus 4.0% o in the placebo-treated individuals. The researchers point out, however, that the trial used rapid dose escalation schedules, with increases every 2 weeks for the first 20 weeks of the trial. This may have influenced the higher dropout rate seen with survodutide and suggests the need for adjustments in future trials, they say.

Such trials also need to include a more diverse study population, suggest Stephen Bain and David Williams, both from Swansea University Medical School in the UK, in a related comment. The mean age of the recruited participants was 49.1 years, 68% were women, and 78% were of White ethnicity.

“The authors also highlighted the beneficial impact of survodutide on cardiovascular risk factors, including both systolic and diastolic blood pressure,” say Bain and Williams. They add that while these were exploratory endpoints, the findings should be considered in the context of the recently published SELECT trial of semaglutide, which was associated with a reduction in major cardiovascular events versus placebo.

“A designated cardiovascular outcomes trial for survodutide will be of particular interest, not only given the chronotropic (and inotropic) effects of glucagon but also the proposed mechanism for additional weight loss to that seen with GLP-1 receptor agonists alone,” say Bain and Williams. Such a trial (SYNCHRONIZE-CVOT) is expected to start recruitment soon.

They conclude: “Further data from large clinical trials are keenly awaited.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group

Lancet Diabetes Endocrinol 2024; 12: 162–173
Lancet Diabetes Endocrinol 2024; 12: 150–151

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