Background: Obesity, a chronic progressive disease, is exacerbated by estrogen deficiency during menopause. Orforglipron (OFG), an oral small-molecule, non-peptide GLP-1 receptor agonist, has demonstrated significant body weight (BW) reductions in ATTAIN-1 and -2. This post-hoc analysis evaluated the association between OFG treatment and BW in women by menopausal stage.
Methods: Female participants with obesity (BMI ≥30kg/m²) or overweight (BMI ≥27kg/m²) with ≥1 obesity-related complication in ATTAIN-1 (without diabetes) and -2 (with diabetes) were analyzed under the efficacy estimand by menopausal status: pre-/peri-/post-menopause. Percent change in BW and change from baseline in waist circumference (WC) were analyzed using a mixed-model repeated measures. Patients achieving BW reduction thresholds (≥5%, ≥10%, ≥15%, and ≥20%) at Week-72 were assessed using logistic regression with multiple imputation. A shift analysis was performed for waist-to-height ratio (WHtR) to summarize changes from baseline to week-72 across menopausal stages.
Results: At baseline, Mean BW for OFG across menopausal stages ranged from 92-108 kg and 93-99 kg in placebo across both studies. Up to 93% of participants in both the OFG and placebo groups had baseline WHtR >0.59. Significantly greater reductions in BW of up to 14% (model-based estimate) and WC 11 cm were observed across subgroups with OFG 36 mg vs PBO (p<0.001) for both studies. With OFG, up to 83% achieved ≥5% BW reduction vs 23% with PBO in the post-menopausal group for ATTAIN-1. Significantly higher proportions of participants taking OFG achieved BW reduction thresholds vs PBO% (p<0.05). At week-72, more OFG-treated participants moved to a lower Waist-to-Height Ratio category (≤0.59) than PBO.
Conclusion: In this post-hoc analysis, OFG treatment in women with obesity or overweight, irrespective of menopausal stage, was associated with significant BW and WC reductions vs PBO. These findings support OFG’s efficacy in managing obesity across different menopausal stages.