Introduction: In the SURMOUNT (SM) clinical trial program, tirzepatide-treatment resulted in substantial and clinically meaningful bodyweight (BW) reductions in people living with overweight and obesity. This post-hoc analysis evaluated the effect of tirzepatide-treatment on BW in women according to menopause stage.
Methods: Women with obesity or overweight from SM-1, -3 and -4 were randomized to tirzepatide (SM-1: 5, 10 or 15 mg; SM-3 and -4: maximum tolerated dose [MTD] of 10 or 15 mg) or placebo. The tirzepatide 15 mg or MTD treatment arms from each study were included in this analysis. Participants were categorized as having pre-menopause, peri-menopause or post-menopause. Premature or artificial menopause, or Mayer-Rokitansky-Küster-Hauser syndrome were excluded from this analysis, as was one participant <40 years with bilateral oophorectomy. Change in BW and waist circumference (WC) and the proportion of participants achieving weight reduction thresholds (≥5%, ≥10%, ≥15%, ≥20% and ≥25%) were assessed at the primary endpoint of 72-weeks (SM-1 and -3) and 88-weeks (SM-4).
Results: Reductions from baseline in BW ranging from 22-29% and WC ranging from 15-26 cm were significant in all menopausal status subgroups with tirzepatide and were significantly greater vs placebo (p<0.001 all). The proportion of participants who achieved BW loss ≥5% was 96-100% with tirzepatide vs 6-78% with placebo across subgroups. Furthermore, 63-89% and 37-74% of participants achieved BW loss ≥20% and ≥25% with tirzepatide, respectively. Overall, a significantly greater proportion of participants from all tirzepatide-treated subgroups exceeded all BW loss thresholds vs placebo.
Conclusion: In this post hoc analysis, women living with obesity or overweight and without type 2 diabetes treated with tirzepatide demonstrated significant BW and WC reductions vs placebo, irrespective of stage of menopausal transition.