Recent analysis of the SURMOUNT trials reveals that tirzepatide, a novel weight loss medication, produces greater weight loss in women compared to men. This finding emerged from a subgroup analysis presented at the European Association for the Study of Diabetes (EASD) annual meeting in Madrid.
Key Findings
Significant Weight Loss: Women experienced up to 24.6% weight loss from baseline, while men lost up to 18.1% (P<0.05). This difference highlights a notable gender disparity in the efficacy of tirzepatide.
Comparison with Placebo: Female participants lost between 11.5% and 27.6% more body weight on tirzepatide compared to placebo, whereas males lost 8.8% to 18.9% more with the drug (P<0.001 for all comparisons with placebo).
Possible Explanations
Luis-Emilio García-Pérez, MD, PhD, from Eli Lilly, noted that the reason for these gender differences is not yet clear. Several hypotheses are being explored, including variations in body fat distribution, body composition, and hormonal differences. García-Pérez also suggested that pharmacological differences might play a role, particularly since tirzepatide’s mechanism involves both GLP-1 and GIP receptors, whereas other drugs like semaglutide focus solely on GLP-1.
Comparative Analysis
Historically, lifestyle interventions have shown different results, with men often losing more weight than women through diet and exercise. This contrasts with the findings for tirzepatide, where women achieved more substantial weight loss. The specific impact of GLP-1 and GIP receptors in tirzepatide could explain these differences. As session moderator Luc Van Gaal, MD, PhD, highlighted, similar effects with semaglutide might indicate a significant role of GLP-1 in this outcome.
Impact of Side Effects
Women also reported higher rates of gastrointestinal side effects, such as nausea and vomiting, compared to men. Despite this, García-Pérez emphasized that these side effects are more prevalent at the start of treatment and do not fully explain the greater weight loss observed in women, as participants continued to lose weight throughout the trials.
Trial Overview
The data comes from the phase III SURMOUNT-1, -2, -3, and -4 trials. These studies tested tirzepatide against placebo over varying periods and patient profiles:
- SURMOUNT-1: Focused on individuals with overweight or obesity without diabetes.
- SURMOUNT-2: Included participants with overweight or obesity plus type 2 diabetes.
- SURMOUNT-3: Examined tirzepatide following a 12-week intensive lifestyle intervention.
- SURMOUNT-4: Evaluated long-term effects with a lead-in period on tirzepatide followed by a placebo-controlled phase.
Future Research Directions
The analysis also noted a higher proportion of female participants across all trials, which could influence the overall results. García-Pérez’s team is now investigating potential differences in weight reduction across various age groups, including reproductive-age, menopausal, and post-menopausal women.
Takeaway
The subgroup analysis of the SURMOUNT trials indicates that tirzepatide is particularly effective for weight loss in women, although both sexes benefit from the medication. While the reasons behind these gender differences remain under investigation, tirzepatide’s efficacy across different populations reinforces its value in managing obesity.
