Orforglipron Reduces Body Weight Up to 14% in Women at Every Stage of Menopause

Menopause-related weight gain has long complicated obesity management in women, but a new post hoc analysis suggests that orforglipron (Foundayo; Eli Lilly)—the only oral glucagon-like peptide-1 receptor agonist (GLP-1 RA) that can be taken without food or water restrictions—delivers meaningful and consistent weight loss across all stages of menopause.

The findings, presented at the 2026 American Diabetes Association (ADA) Scientific Sessions in New Orleans, Louisiana, add important context to the growing body of evidence supporting orforglipron's role in obesity pharmacotherapy and have clear implications for pharmacists counseling women on weight management options.^1,2

What the Post-Hoc Analysis Found

The analysis pooled female participants from ATTAIN-1 and ATTAIN-2—pivotal phase 3 trials evaluating orforglipron in adults with obesity or overweight—and stratified them by menopausal status: premenopausal, perimenopausal, and postmenopausal. All participants had a body mass index (BMI) of at least 30 or a BMI of at least 27 with 1 or more obesity-related complications. Outcomes were assessed at 72 weeks using the efficacy estimand and included changes in body weight, waist circumference (WC), and waist-to-height ratio (WtHR), as well as the proportions of participants achieving body weight reduction thresholds of at least 5%, 10%, 15%, and 20%.^1,2

Across all 3 menopausal subgroups, orforglipron produced statistically significant reductions in body weight of up to 14% and WC reductions of up to 11 cm compared with placebo (P < .001). Up to 83% of women receiving orforglipron achieved at least a 5% reduction in body weight compared with 23% in the placebo group. Significantly higher proportions of orforglipron-treated participants reached each of the body weight reduction thresholds relative to placebo (P < .001). Additionally, more participants treated with orforglipron moved to lower WtHR categories than those receiving placebo, a clinically meaningful indicator given the well-established relationship between visceral adiposity and cardiometabolic risk in menopausal women.¹

Menopause and Obesity: A Compounding Challenge

The menopause transition and postmenopausal period are characterized by physiologic changes driven by estrogen decline that pose significant health risks across multiple organ systems, with obesity prevalence during and after menopause representing a substantial clinical concern. Estrogen deficiency is associated with increased visceral adiposity and decreased energy expenditure, and treatment approaches must account for hormonal influences on appetite regulation and metabolism.^3,4

Approximately two-thirds of women aged 40 to 59 years and three-fourths of those older than 60 years in the US are classified as overweight, and nearly half of women in both age groups are obese. Midlife weight gain promotes cardiovascular disease, the primary cause of death in postmenopausal women, and increases the frequency of vasomotor symptoms, sexual dysfunction, and mood disorders. Despite this, evidence specifically evaluating GLP-1 RA efficacy by menopausal stage has been limited until now.^3,4

ATTAIN-1 and ATTAIN-2: The Foundation

The post hoc findings build on robust pivotal trial data. In ATTAIN-1, a phase 3 randomized, double-blind, placebo-controlled trial in adults with obesity without diabetes, participants taking the highest dose of orforglipron experienced an 11.2% reduction (95% CI, -12.0% to -10.4%) at 72 weeks, with the drug also demonstrating significant improvements across key cardiometabolic risk factors. In adults with obesity, 72-week treatment with orforglipron led to significantly greater reductions in body weight than placebo, with an adverse event profile consistent with other GLP-1 RAs. In ATTAIN-2, which enrolled adults with obesity or overweight and type 2 diabetes—a population with well-recognized challenges in weight management—participants lost an average of 22.9 lbs (10.5%) on the highest dose, with hemaglobin A_1c significantly improved. Both trials met their primary and all key secondary end points.^5,6

Implications for Pharmacist-Led Care

As one of the most accessible health care professionals, pharmacists can play a key role in counseling women on the risks and benefits of prescription options to prevent unnecessary weight gain and in making timely referrals that can improve overall health. The ADA 2026 post hoc data add a meaningful dimension to those conversations: pharmacists can now counsel patients that orforglipron's efficacy appears consistent regardless of menopausal stage, addressing a common patient concern that hormonal changes may blunt pharmacotherapy outcomes.^4,7

The absence of food and water administration restrictions also removes a practical barrier that may otherwise affect adherence in busy midlife patients managing complex schedules and polypharmacy regimens. As pharmacists become increasingly embedded in obesity and diabetes management, through medication therapy management, collaborative practice agreements, and direct prescribing authority in some states, awareness of subgroup-specific evidence like these ADA findings positions them to deliver more individualized, evidence-based care.^4,7

REFERENCES

1. Ciudin A, Tchang B, Balmain AJ, et al. Menopausal stage and weight outcomes with orforglipron vs placebo: Post hoc subgroup analysis from ATTAIN-1 and ATTAIN-2. Presented at: 2026 American Diabetes Association Scientific Sessions; June 5-8, 2026; New Orleans, LA. Accessed Via Online ADA Scientific Sessions Portal.

2. Lilly's Foundayo (orforglipron), the only oral GLP-1 taken without food or water restrictions, was associated with significant weight loss in women at every stage of menopause. News Release. Released June 7, 2026. Accessed June 10, 2026. https://investor.lilly.com/news-releases/news-release-details/lillys-foundayo-orforglipron-only-oral-glp-1-taken-without-food

3. Hurtado MD, Saadedine M, Kapoor E, et al. Weight gain in midlife women. Curr Obes Rep. 2024;13(2):352-363. doi:10.1007/s13679-024-00555-2

4. Olavessen-Holt K. Perimenopausal and postmenopausal weight-loss challenges. US Pharm. 2025;50(12):41-46. https://www.uspharmacist.com/article/perimenopausal-and-postmenopausal-weightloss-challenges

5. Wharton S, Aronne LJ, Stefanski A, et al; ATTAIN-1 Trial Investigators. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment. N Engl J Med. 2025;393(18):1796-1806. doi:10.1056/NEJMoa2511774

6. Horn DB, Ryan DH, Kis SG, et al; ATTAIN-2 Trial Investigators. Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. Lancet. 2026;406(10522):2927-2944. doi:10.1016/S0140-6736(25)02165-8

7. Chamarthi VS, Daley SF. Special populations and long-term management in obesity medicine. StatPearls. Updated September 2, 2025. https://www.ncbi.nlm.nih.gov/books/NBK618379/