CagriSema Tied to 25% Weight Loss in Women, Post Hoc Data Show

Women with obesity or overweight who received investigational cagrilintide and semaglutide (CagriSema; Novo Nordisk) lost an average of 25.0% of their body weight at 68 weeks. Weight loss stayed substantial whether they were premenopausal, perimenopausal, or postmenopausal, according to 2 post hoc analyses of the phase 3 REDEFINE 1 trial (NCT05567796). The analyses were presented at The Menopause Society 2026 Annual Meeting in San Diego, California.¹

An FDA decision on the once-weekly injection is expected in the fourth quarter of 2026, so the data give pharmacists an early look at outcomes in women, who made up approximately two-thirds of trial participants.¹

Weight Loss Among All Women in REDEFINE 1

REDEFINE 1 was a 68-week, double-blind trial with both placebo and active comparators. It randomly assigned 3417 adults without diabetes to once-weekly cagrilintide 2.4 mg plus semaglutide 2.4 mg, semaglutide alone, cagrilintide alone, or placebo, plus lifestyle interventions for all groups. Participants had a body mass index (BMI) of 30 or higher or a BMI of 27 or higher with at least 1 obesity-related complication. The primary trial report used the treatment-policy estimand. By that measure, mean body weight change at week 68 was -20.4% with the combination versus -3.0% with placebo.²

The first post hoc analysis included all 2309 women enrolled in the trial. Mean weight reduction at week 68 was:

• 25.0% with CagriSema;
• 19.0% with semaglutide alone;
• 13.4% with cagrilintide alone; and
• 3.0% with placebo.

Waist circumference, a marker of abdominal fat, decreased by 20.5 cm with CagriSema versus 4.7 cm with placebo. Among women receiving CagriSema, 93.3% lost at least 10% of their body weight and 68.7% lost at least 20%. Among women receiving placebo, those figures were 12.7% and 1.8%, respectively.¹

These figures reflect the efficacy estimand, which assumes all participants stayed on treatment and used no other weight loss therapies. They are therefore not directly comparable to the treatment-policy results in the primary publication. P values were not adjusted for multiplicity, and formal treatment-by-sex interaction testing was not performed.¹

Results by Menopause Stage

The second analysis grouped 1902 women who received CagriSema or placebo by menopause status. Investigators assigned status after the fact, using age, medical history, and recorded symptoms. It was not based on reproductive staging collected during the trial or on biochemical confirmation. Mean weight loss with CagriSema versus placebo was:

• Premenopausal women: 26.7% versus 2.1%;
• Perimenopausal women: 24.8% versus 1.7%; and
• Postmenopausal women: 23.1% versus 2.6%.

Women using hormone therapy were evaluated as a separate group, but the company release did not report results for that group.¹

Lead author Maria D. Hurtado Andrade, MD, PhD, an assistant professor at Mayo Clinic Alix School of Medicine, called the weight loss in each group "encouraging." She said the numerical differences among groups point to a need for further research on how reproductive aging may influence weight loss outcomes in women.¹

"Pharmacists can counsel women that incretin-based therapies are effective across reproductive life stages," Hurtado Andrade said in a comment to Pharmacy Times. "Available data suggest that postmenopausal women may experience slightly less weight loss than premenopausal women, but the overall degree of weight loss remains substantial and clinically meaningful."

Weight gain and a shift toward central fat distribution are common among women in midlife. Aging, declining estrogen levels after menopause, and other factors drive these changes. Central obesity carries metabolic consequences, including dysglycemia, dyslipidemia, hypertension, and cardiovascular disease.³

"Because CagriSema may produce rapid and substantial weight loss, close follow-up will be important, particularly in midlife and older women," Hurtado Andrade said. "Pharmacists should emphasize adequate protein intake, resistance exercise, and appropriate nutritional support while monitoring for excessive loss of lean mass and potential adverse effects on bone health. These considerations are particularly relevant after menopause, when women are already at increased risk for loss of muscle and bone mass."

Safety and Counseling Considerations

Gastrointestinal adverse events were the most common safety signal in REDEFINE 1. They affected 79.6% of participants receiving the combination versus 39.9% receiving the placebo and were mainly transient and mild to moderate in severity. According to Novo Nordisk, the rates with the combination versus placebo were:

• Nausea: 55% versus 12.6%;
• Constipation: 30.7% versus 11.6%;
• Vomiting: 26.1% versus 4.1%; and
• Discontinuation due to adverse events: 5.9% versus 3.5%.^1,2

"Ideally, patients should be reassessed within 4–6 weeks after treatment initiation and have additional touchpoints following dose increases, particularly if symptoms develop," Hurtado Andrade said. "Treatment should be individualized, and dose escalation can be slowed or delayed in patients experiencing significant gastrointestinal adverse effects rather than automatically advancing the dose."

Pharmacists can also counsel patients on nonpharmacologic strategies, she noted, including eating smaller meals, eating slowly, stopping when full, maintaining adequate hydration, and avoiding foods or meal patterns that worsen symptoms. "The goal should be to identify the lowest effective and well-tolerated dose while supporting long-term treatment adherence," she said.

Regulatory Status

Novo Nordisk filed a New Drug Application with the FDA for CagriSema for weight management in December 2025, and a decision is expected in the fourth quarter of 2026. CagriSema is not approved in the United States. The company described the post hoc analyses as hypothesis generating.^1,2

REFERENCES

1. Novo's CagriSema was associated with 25% weight loss on average for women in a post hoc analysis of REDEFINE 1 presented at The Menopause Society Annual Meeting. News release. Novo Nordisk. October 20, 2026. Accessed October 21, 2026. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=918570&utm_source=linkedin&utm_theme=sci_inn&utm_medium=social&utm_campaign=2026-media-release&utm_content=menopause-society-meeting

2. Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity. N Engl J Med. 2025;393(7):635-647. doi:10.1056/NEJMoa2502081

3. Kapoor E, Collazo-Clavell ML, Faubion SS. Weight gain in women at midlife: a concise review of the pathophysiology and strategies for management. Mayo Clin Proc. 2017;92(10):1552-1558. doi:10.1016/j.mayocp.2017.08.004