Weight loss varies with investigational triple agonist for adults with obesity
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Key takeaways:
- Weight loss for adults with obesity receiving retatrutide is heterogenous and varies based on demographics.
- Women, younger adults and those with a higher BMI lose more weight with retatrutide in a phase 2 trial.
DALLAS — Weight loss with the triple-hormone agonist retatrutide varies by sex, age and baseline BMI, according to a speaker.
As Healio previously reported, retatrutide (Eli Lilly) is a once-weekly injectable GLP-1/glucose-dependent insulinotropic polypeptide (GIP)/glucagon triple-hormone agonist in development for the treatment of obesity. In a phase 2 trial, adults with obesity who received 12 mg retatrutide weekly lost 24.2% of their body weight at 48 weeks. However, a subgroup analysis of the phase 2 data presented at ObesityWeek revealed weight loss with retatrutide can vary based on several factors.
“In this phase 2 study, sex, baseline BMI and age predicted the degree of mean weight reduction response to retatrutide intervention,” Ania M. Jastreboff, MD, PhD, associate professor of medicine and pediatrics (endocrinology) at Yale University School of Medicine, director of the Yale Obesity Research Center and co-director of the Yale Center for Weight Management, said during a presentation. “With this intervention, the mean percent weight reduction was significantly greater for [women than men], for those with more severe obesity and for those who were younger.”
In the phase 2 trial, 338 adults without diabetes who had a BMI of 30 kg/m2 or greater or BMI of 27 kg/m2 or higher with at least one obesity-related comorbidity were randomly assigned to 1 mg, 4 mg, 8 mg or 12 mg retatrutide or placebo once weekly for 48 weeks (mean age, 48.2 years; 51.8% men; mean BMI at baseline, 37.3 kg/m2). In the subgroup analysis, weight loss was analyzed based on sex, baseline BMI and age. Adults in the 4 mg, 8 mg and 12 mg retatrutide groups were included in the pooled analysis. Mean placebo-adjusted percent weight change was calculated for each subgroup.
In the sex subgroup analysis, men lost up to 21.9% of their body weight with 8 mg retatrutide during the trial. For women, the maximum mean weight loss was 28.5% in the 8 mg group. Women had a greater placebo-adjusted body weight reduction of 4.2% compared with men (P = .019).
“The purposeful inclusion of approximately equal percentages of men and women may have dampened the overall efficacy results of this trial compared to trials that enrolled higher percentages of women,” Jastreboff said.
For baseline BMI, adults were separated into a group with a baseline BMI of less than 35 kg/m2 (n = 144) and a group with a baseline BMI of 35 kg/m2 or higher (n = 194). Adults with a lower baseline BMI lost up to 22.1% of their body weight in one of the 8 mg retatrutide groups. Adults with a higher baseline BMI lost up to 26.5% with one of the 8 mg retatrutide groups. In pooled analysis, adults with a baseline BMI of 35 kg/m2 or higher had a 4.2% greater weight loss than those with a baseline BMI of less than 35 kg/m2 (P = .022).
For the age subanalysis, participants were divided into one group aged 50 years and older (n = 167) and a second group younger than 50 years (n = 171). Older adults had up to a 22.9% mean weight loss with 12 mg retatrutide and younger adults had up to a 27.4% weight loss in one of the 8 mg retatrutide groups. The placebo-adjusted mean weight loss was 6.9% higher for younger adults compared with older adults (P < .001).
In an analysis of subgroups by sex and BMI, men with a BMI of 35 kg/m2 or higher had a 5.4% greater weight reduction than men with a BMI of less than 35 kg/m2 (P = .02). When age and sex were both analyzed, men younger than 50 years lost 10.3% more body weight than men aged 50 years and older (P < .001), and women aged 50 years and older lost 8% more body weight than men aged 50 years and older (P = .002).
Among the clinical factors examined, sex was associated with the largest difference in weight reduction, followed by BMI and age.
“These observations warrant further examination in larger phase 3 trials of retatrutide, which are currently underway,” Jastreboff said.
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Jastreboff AM, et al. Oral-055. Presented at: ObesityWeek; Oct. 14-17, 2023; Dallas.
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