1716-P
Menopausal Stage and Weight Outcomes with Orforglipron vs Placebo Post-Hoc Subgroup Analysis from ATTAIN-1 and ATTAIN-2

Authors: Andreea Ciudin1, Beverly G. Tchang2, Amelia J. Balmain3, Suzanne Klise3Donna Mojdami3, Wenyu Ye3, Xiaojuan Mi4, Hunter T. Hoffmann3


1.Hospital Universitari Vall d'Hebron, Barcelona, Spain
2.Comprehensive Weight Control Center, Weill Cornell Medicine, New York, NY, USA
3.Eli Lilly and Company, Indianapolis, IN, USA
4.TechData Services Company, King of Prussia, PA, USA

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Sponsored by Eli Lilly and Company

Objective
  • This post-hoc analysis of ATTAIN-1 and ATTAIN-2 evaluated the relationship of orforglipron treatment and body weight in females, stratified by menopausal stage.
Conclusions
  • At Week 72, regardless of menopausal stage, participants on orforglipron 36 mg had
    significantly greater reductions in percent body weight (BW) and waist circumference versus
    placebo.
  • Compared to placebo, significantly more participants on orforglipron 36 mg achieved a
    majority of BW reduction threshold targets.
  • When comparing waist-to-height ratio (WHtR), a greater percentage of females on orforglipron
    36 mg achieved a lower WHtR at Week 72 compared to placebo.
  • Orforglipron supports weight reduction in females across the spectrum of menopausal stages,
    demonstrated in both ATTAIN-1 and ATTAIN-2.
Background
  • Estrogen deficiency in menopause can increase the risk of obesity and cardiometabolic outcomes.1,2,3
  • Orforglipron (OFG) is a small molecule, novel, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist administered once daily orally.
  • OFG is FDA-approved to reduce excess body weight and maintain weight reduction long-term in adults with obesity or overweight with ≥1 obesity-related complication in combination with a reduced-calorie diet and increased physical activity, and is being investigated for use in type 2 diabetes.4
  • Both ATTAIN-1 and ATTAIN-2 demonstrated significant reductions in body weight (BW) in adults with obesity and with or without type 2 diabetes, compared to placebo (PBO).5,6
  • Due to the impact of menopause on obesity and cardiometabolic risk, the impact of OFG on BW outcomes is of interest in this population.
Study design and participants
ATTAIN-1 (Phase 3, Multinational, Randomized Double-Blind Trial)5

OFG 6, 12, 36 mg QD (N=2178) Vs PBO QD (N=949)

  • Duration: 72 weeks
  • Adults with obesity (defined as BMI ≥30 kg/m2) or overweight (BMI 27 to 30 kg/m2) with ≥1 obesity-related complication
  • Key exclusion: Diabetes (type 1 or type 2)
  • Adjunct to a healthy diet and physical activity
ATTAIN-1 (Phase 3, Multinational, Randomized Double-Blind Trial)6

OFG 6, 12, 36 mg QD (N=983) vs PBO QD (N=630)

  • Duration: 72 weeks
  • Adults with BMI ≥27 kg/m2 and pre-existing type 2 diabetes
  • Key exclusion: Any other type of diabetes except type 2 diabetes
  • Adjunct to a healthy diet and physical activity
N: number of participants in the population in the specified treatment group. OFG capsule formulations of 6 mg, 12 mg, and 36 mg doses have been shown as the equivalent tablet doses of 5.5 mg, 9 mg, and 17.2 mg, which are approved in the United States.7 Abbreviations: BMI: body mass index; QD: once daily
Methods

  • Post-hoc analysis: included females with menopausal status (pre, peri, post): N=2003 from ATTAIN-1 and N=754 from ATTAIN-2.

  • All treatment arms included in analyses, but reported OFG 36 mg and PBO in this document.

  • Presents data from the investigational OFG capsule formulation of 36 mg. The dose has been shown as the equivalent tablet dose of 17.2 mg, which is approved in the United States. 7

  • Outcomes (analyses guided by efficacy estimand):

    • Change from baseline to Week 72 in percent BW reduction and waist circumference.
    • Proportion of participants achieving BW reduction threshold targets at Week 72 (≥5%, ≥10%, ≥15%, ≥20%).
    • Proportion of participants in each waist-to-height ratio (WHtR) category at baseline and Week 72 by treatment group.
Menopausal Staging
  • Pre-menopausal: Aged <45 years without any indication of menopause.
  • Peri-menopausal: Aged ≤54 years with diagnosis of menopausal symptoms or evidence for clinical suspicion for menopause but not satisfying criteria for post-menopause; or aged 45–54 with no evidence for menopause.
  • Post-menopausal: Aged ≥40 years with documented medical history indicating menopause, or follicle stimulating hormone (FSH) ≥40 mIU/mL without hormone replacement therapy, or being aged ≥55 years.

Baseline Demographics and Clinical Characteristics

ATTAIN-1_and_ATTAIN-2_baseline_demographics
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Data are mean ± SD or n (%) at baseline. N: number of participants, n: number of participants in specified group. Note: Presents data from the investigational OFG capsule formulation of 36 mg. Dose has been shown as the equivalent tablet dose of 17.2 mg, which is approved in the United States.7 Abbreviations: BMI: body mass index; BW: body weight; HbA1c: glycated hemoglobin; OFG: orforglipron; ORCs: obesity-related complications; PBO: placebo; PCOS: polycystic ovary syndrome; SD: standard deviation; WHtR: waist-to-height ratio.
Key Results
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Panel A: Data are MBE (SE) percent change from baseline in BW and change from baseline in waist circumference at the primary endpoint (Week 72). Analyzed using MMRM adjusted for stratification factors and baseline value.

Panel B: Data are MBE proportion of achieving body weight reduction targets (%) (SE) at Week 72. MBE for endpoint measures are from logistic regression model using imputed data, adjusted for stratification factors and baseline values.

Note: Presents data from the investigational OFG capsule formulation of 36 mg. The dose has been shown as the equivalent tablet dose of 17.2 mg, which is approved in the United States.⁷

Abbreviations: BW: body weight; MBE: model-based estimate; MMRM: mixed model for repeated measure; OFG: orforglipron; PBO: placebo; Peri: peri-menopausal; Pre: pre-menopausal; Post: post-menopausal; SE: standard error. *p<0.05 and **p<0.001 OFG 36 mg vs PBO.

Additional Results

ATTAIN-1_and_ATTAIN-2_Additional_Results
Proportion of participants in each WHtR category at baseline to Week 72, by menopausal stage and treatment group. Includes only participants with a baseline value and ≥1 post-baseline WHtR measurement. N= total participants per treatment group within menopausal stage; n= participants in each WHtR category; Abbreviations: OFG: orforglipron; PBO: placebo; Peri: peri-menopausal; Pre: pre-menopausal; Post: post-menopausal; WHtR: waist-to-height ratio; Wk 72: Week 72; Presents data from the investigational OFG capsule formulation of 36 mg. The dose has been shown as the equivalent tablet dose of 17.2 mg, which is approved in the United States.⁷
References
  • Carr MC. J Clin Endocrinol Metab. 2003;88(6):2404-2411.
  • Ko SH, Jung Y. Nutrients. 2021;13(12):4556.
  • Kirtikar U, Kajale N, Patwardhan V, Khadilkar V, Khadilkar AV. J Midlife Health. 2020;11(1):22-26.
  • Eli Lilly and Company. Foundayo® (orforglipron) prescribing information. 2026. Available at: https://pi.lilly.com/us/foundayo-uspi.pdf.
  • Wharton S, Aronne LJ, Stefanski A, et al. N Engl J Med. 2025;393(18):1796-1806.
  • Horn DB, Ryan DH, Kis SG, et al. Lancet. 2026;406(10522):2927-2944.
  • Ma X, Li YG, Raha S, Sperry DC, Coutant DE, Bhattachar S. Diabetes Obes Metab. 2026.

Acknowledgments: The authors would like to thank Lindsey Anderson, PharmD (Eli Lilly and Company) for their writing and editorial contributions.

Disclosures: AC reports receiving speaking fees from Astra Zeneca, Boehringer-Ingelheim, Eli-Lilly, Novo Nordisk, Sanofi, Menarini and research grants from Eli Lilly, NovoNordisk and Menarini. AC reports as a member of the DMC of Boehringer Ingelheim. BGT reports current or past consulting/advisor fees from Novo Nordisk, Roman Health Ventures, Skye Bioscience, Circadian Care, Amgen, Lilly, Boehringer-Ingelheim, Gelesis, Cloud Health Systems, SAI MedPartners, Tern Pharmaceuticals, and Intellihealth/Flyte Health. XM is an employee of TechData Services, which is in contract with Eli Lilly and Company. AB, SK, DM, WY, and HH are employees and stockholders of Eli Lilly and Company.

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