Subgroup analysis by sex and baseline BMI in people with a BMI ≥27 kg/m<sup>2</sup> in the phase 2 trial of survodutide, a glucagon/GLP-1 receptor dual agonist.
This paper reports a prespecified subgroup analysis from a phase 2 randomized controlled trial examining how sex and baseline BMI influenced the efficacy and safety of survodutide, a dual glucagon/GLP-1 receptor agonist, in adults without diabetes who had a BMI ≥27 kg/m². A total of 387 participants were randomized to one of four once-weekly subcutaneous survodutide doses or placebo over 46 weeks, which included a 20-week dose-escalation phase followed by a 26-week maintenance phase. The study found that, across survodutide-treated groups, females experienced greater reductions in both bodyweight and waist circumference compared with males. Participants who started with a lower baseline BMI showed proportionally greater bodyweight reductions, while those with a higher baseline BMI showed greater absolute reductions in waist circumference. Adverse event rates were broadly comparable across sex and BMI subgroups, with nausea being the most common gastrointestinal side effect reported in all subgroups. Key limitations include the descriptive (non-inferential) nature of the subgroup analyses, the relatively modest sample size when subdivided by subgroup, and potential confounding from COVID-19-related treatment discontinuations. These findings suggest differential responses by sex and baseline BMI, but the subgroup design limits causal conclusions.
Why this grade: While drawn from a phase 2 RCT in humans, this paper presents descriptive subgroup analyses with reduced per-subgroup sample sizes and no formal inferential statistical testing, limiting the strength of evidence for subgroup-specific conclusions.
Aim To explore the effects of sex and baseline body mass index (BMI) on the efficacy and safety of survodutide in people with a BMI ≥27 kg/m 2 . Materials and methods Totally 387 people (aged 18-75 years, BMI ≥27 kg/m 2 , without diabetes) were randomized 1:1:1:1:1 to once-weekly subcutaneous survodutide (0.6, 2.4, 3.6 or 4.8 mg) or placebo for 46 weeks (20-week dose escalation; 26-week dose maintenance). Participants were categorized according to sex and baseline BMI. Data were analysed descriptively for the full analysis set (FAS), according to dose assigned at randomization (planned treatment) using on-treatment data or all data censored for COVID-19-related treatment discontinuations. (ClinicalTrials.gov number: NCT04667377). Results After 46 weeks of survodutide treatment, females had greater reductions in bodyweight and waist circumference than males. Participants with a lower baseline BMI had greater proportional reductions in bodyweight than those with a higher baseline BMI; the trend was reversed for reductions in waist circumference. Rates of adverse events (AEs) were comparable between subgroups for sex and baseline BMI. Nausea was the most frequently reported gastrointestinal AE in all subgroups. Conclusions In people with a BMI ≥27 kg/m 2 , survodutide was associated with clinically meaningful reductions in bodyweight and waist circumference when compared with placebo, in prespecified subgroups based on sex and baseline BMI, and was tolerated at all doses tested.
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