CagriSema Reduces Weight in Women Across Menopause Stages, HT Use

A post-hoc analysis of the REDEFINE 1 trial suggests that the investigational cagrilintide-semaglutide combination (CagriSema) delivers clinically meaningful weight loss in women across all menopause stages and among those using hormone therapy (HT).¹

The analysis found weight reductions of 23% to 27% across every reproductive life stage studied, along with improvements in blood pressure, fasting glucose, and triglycerides, according to data presented at The Menopause Society's 2026 Annual Meeting.

“CagriSema [is] a combination of the GLP-1 receptor agonist semaglutide plus the long-acting amylin cagrilintide, so 2 different mechanisms of actions, 2 different compounds, both affecting appetite in an additive way,” said Timothy Garvey, MD, professor of medicine in the Department of Nutrition Sciences at the University of Alabama at Birmingham, according to Metabolic Care Today.² “So you add the cagrilintide to the semaglutide, you get additive weight loss into a very nice range of efficacy. The thing about the cagrilintide, [because] we’re all worried about tolerability, it’s very well-tolerated compared [with] the GLP-1.”

In the REDEFINE 1 post-hoc analysis, investigators evaluated 1902 women aged 18 to 81 with overweight or obesity across 4 cohorts comprising pre-menopause, peri-menopause, post-menopause, and HT use. Over 68 weeks, CagriSema achieved substantial weight loss across all groups, with mean reductions of 26.7% in pre-menopause, 24.8% in peri-menopause, 23.1% in post-menopause, and 25.6% with HT.¹

READ MORE: EloraTZP Shows Greater Weight Loss, A1C Reduction Than Tirzepatide

Between 91% and 95.1% of participants reached at least 10% weight loss, while 63.2% to 78.3% achieved at least a 20% reduction. Waist circumference decreased between 19.2 and 21.7 centimeters, and significant improvements occurred in blood pressure, fasting glucose, and triglycerides regardless of reproductive stage or HT use.

Neurological Signaling and Ectopic Fat Reduction

Recent neuroimaging and organ-specific analyses offer valuable mechanistic context for pharmacists addressing patient questions regarding appetite and weight-loss quality.³

Functional magnetic resonance imaging over 52 weeks showed that CagriSema altered neural responses to high-calorie food cues in brain centers regulating reward and craving, significantly reducing intrusive food noise and hunger. Additionally, magnetic resonance imaging substudies in type 2 diabetes demonstrated significant reductions in ectopic fat surrounding the liver and pancreas alongside abdominal visceral fat loss.

A systematic review and meta-analysis of 8 randomized trials involving 6898 participants reinforced these findings, showing that CagriSema achieved significantly greater weight reductions compared with semaglutide monotherapy, cagrilintide monotherapy, and placebo. The meta-analysis also confirmed marked improvements in glycated hemoglobin, waist circumference, and blood pressure.⁴

Comparative Efficacy and Safety Profile

These metabolic benefits emerge amidst a rapidly evolving landscape for multi-agonist compounds. In the head-to-head phase 3 REDEFINE 4 trial involving 809 participants, CagriSema produced a 23% mean weight loss over 84 weeks, though it did not achieve noninferiority against the highest 15 mg dose of tirzepatide, which achieved 25.5%.^5,6

Across clinical investigations, adverse events were predominantly gastrointestinal (GI), including nausea and diarrhea. These symptoms were mostly mild to moderate, transient, and waned over time. Furthermore, pooled meta-analysis data confirmed that despite GI events occurring more frequently with the dual agonist, serious adverse events did not significantly differ between CagriSema and active monotherapies or placebo.^3-5

Considerations for Clinical Pharmacy Practice

For pharmacists navigating obesity care, these findings highlight vital opportunities for clinical guidance. At the American Pharmacists Association 2026 Annual Meeting, Emily Eddy, PharmD, emphasized that multi-agonist therapies are transforming practice by treating underlying cardio-kidney-metabolic health rather than isolated glycemic numbers.^5,6

Pharmacists must actively monitor patients experiencing rapid weight reduction for potential lean muscle loss of 15% to 25% and screen for micronutrient deficiencies in vitamins D and B12.⁶

With an FDA decision anticipated in late 2026, pharmacists will play a central role in counseling women on individualized multi-agonist therapy across reproductive stages.^3,5

“Women treated with CagriSema showed clinically meaningful body weight reductions across all subgroups examined in this post hoc analysis (means ranging from 23.1% to 26.7%); observed improvements in blood pressure, FPG, and triglycerides were significant in all subgroups, whereas changes in cholesterol were variable,” concluded authors of the meeting poster.¹ “Weight reduction was numerically greater in pre- versus peri- and post-menopausal women, and a greater proportion of pre-menopausal women had ≥20% body weight reduction versus the other two reproductive life stage groups, though no formal treatment by subgroup interactions were tested.”

READ MORE: Diabetes Resource Center

REFERENCES

1. Hurtado Andrade MD, Martins Mazini Tavares C, Contreras CKO, et al. Effect of CagriSema on body weight reduction and cardiometabolic risk factors in women by menopause status and hormone therapy use: a post hoc analysis of the REDEFINE 1 trial.; 2026:P-50. Presented at: The Menopause Society 2026 Annual Meeting; October 20-24, 2026; San Diego, CA.

2. Garvey WT. The emerging role of amylin: Dr. Garvey on CagriSema and the future of obesity care. Metabolic Care Today. July 20, 2026. Accessed October 23, 2026. https://www.docwirenews.com/videos/the-emerging-role-of-amylin-dr-garvey-on-cagrisema-and-the-future-of-obesity-care

3. Halpern L. CagriSema curbs 'food noise,' organ fat in patients with obesity, T2D respectively. Pharmacy Times. October 2, 2026. Accessed October 23, 2026. https://www.pharmacytimes.com/view/cagrisema-curbs-food-noise-organ-fat-in-patients-with-obesity-t2d-respectively

4. Shao C, Lin H, Yu J, et al. Efficacy and safety of CagriSema for metabolic outcomes: systematic review and pairwise meta-analysis of randomized controlled trials. Diabetes Metab Syndr Obes. 2026;19:616418. 2026 Sep 15. doi:10.2147/DMSO.S616418

5. Gallagher A. CagriSema did not meet primary end point of noninferiority to tirzepatide. Drug Topics. February 24, 2026. Accessed October 23, 2026. https://www.drugtopics.com/view/cagrisema-did-not-meet-primary-end-point-of-noninferiority-to-tirzepatide

6. Nowosielski B. GLP-1s taking over indications outside of diabetes and weight-loss | APhA 2026. Drug Topics. April 6, 2026. Accessed October 23, 2026. https://www.drugtopics.com/view/glp-1s-taking-over-indications-outside-of-diabetes-and-weight-loss-apha-2026