CagriSema Cuts Weight Up to 27% Across Menopause Stages: TMS 2026

Investigational CagriSema was associated with mean weight reductions ranging from 23.1% to 26.7% across menopause stages at 68 weeks, with additional improvements in waist circumference and cardiometabolic risk factors, according to 2 post hoc analyses of the phase 3 REDEFINE 1 trial presented at The Menopause Society 2026 Annual Meeting, held October 20-24 in San Diego, California.¹˒²

Among women receiving CagriSema 2.4 mg/2.4 mg, mean body weight reductions were 26.7% in premenopausal women, 24.8% in perimenopausal women, and 23.1% in postmenopausal women, compared with 2.1%, 1.7%, and 2.6%, respectively, among placebo recipients. Women using menopause hormone therapy (HT) experienced a mean weight reduction of 25.6% with CagriSema, compared with 2.3% with placebo.¹

In a separate analysis of 1902 women randomized to CagriSema or placebo, participants receiving the investigational combination experienced a mean 25.0% reduction in body weight at week 68, compared with 3.0% with placebo (estimated treatment difference [ETD], −22.1 percentage points; 95% CI, −22.6 to −21.5; P < .0001).²

CagriSema combines cagrilintide, a long-acting amylin analog, with the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide. The once-weekly injectable therapy is being investigated for chronic weight management and was not FDA approved at the time of the October 20 presentation.³

"Many women with obesity or overweight experience weight gain as they move through menopause, and it is important to explore investigational products such as CagriSema across the reproductive lifespan," Michelle Skinner Moore, PharmD, MBA, interim head of clinical development, medical and regulatory affairs and vice president of medical affairs at Novo Nordisk, said in a press release.³

The analyses were led by Maria D. Hurtado Andrade, MD, PhD, assistant professor at Mayo Clinic Alix School of Medicine, and evaluated weight loss and cardiometabolic outcomes among women participating in REDEFINE 1 (NCT05567796), a 68-week, double-blind, placebo- and active-controlled phase 3a trial.

The parent trial enrolled 3417 adults with a body mass index (BMI) of at least 30 kg/m², or at least 27 kg/m² with 1 or more obesity-related complications, without type 2 diabetes. Participants were randomized to CagriSema 2.4 mg/2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo alongside lifestyle intervention.¹˒²

Weight Loss Exceeded 20% Across Menopause Stages

In the menopause-specific analysis, investigators evaluated 1902 women who received CagriSema (n=1441) or placebo (n=461), categorizing participants according to menopause status and HT use.

Menopause status was determined retrospectively using age, medical history, menstrual patterns, and documented symptoms. Women using HT were evaluated as a separate group regardless of age or menopause status.¹˒³

At week 68, CagriSema was associated with substantial weight reductions across all 4 groups. Premenopausal women receiving CagriSema experienced a mean 26.7% reduction in body weight, compared with 2.1% among placebo recipients. Corresponding reductions were 24.8% versus 1.7% among perimenopausal women and 23.1% versus 2.6% among postmenopausal women. Among women receiving HT, mean weight loss was 25.6% with CagriSema compared with 2.3% with placebo.¹

At least 20% body weight reduction was achieved by 78.3% of premenopausal women, 70.4% of perimenopausal women, 63.2% of postmenopausal women, and 69.4% of HT users receiving CagriSema. Corresponding placebo response rates were 3.0%, 1.2%, 2.2%, and 1.8%, respectively.¹

The proportion achieving at least 10% body weight reduction was also consistently high across groups, ranging from 91.0% among HT users to 95.1% among premenopausal participants receiving CagriSema.

Although weight loss was numerically greater among premenopausal women, investigators did not conduct formal treatment-by-subgroup interaction testing. Consequently, the findings do not establish that menopause status or HT use significantly modifies the weight loss response to CagriSema.

"This post hoc analysis from REDEFINE 1 offers new insight into weight loss with investigational CagriSema in women grouped by reproductive life stage," Hurtado Andrade said in the press release. "The weight loss observed in each group is encouraging, and the numerical differences among the groups highlight the need for further research to better understand how reproductive aging may influence weight loss outcomes in women."³

Nearly 7 in 10 Women Achieved at Least 20% Weight Loss

In the second analysis, investigators evaluated outcomes among the 1902 women receiving CagriSema or placebo, irrespective of menopause status.²

At week 68, 93.3% of CagriSema recipients achieved at least 10% weight loss, compared with 12.7% receiving placebo. Nearly 7 in 10 women receiving CagriSema achieved at least 20% weight loss (68.7% vs 1.8%), while 29.5% achieved at least 30% weight loss, compared with 0.3% receiving placebo (all P<.0001).²

The findings also showed significant reductions in central adiposity and several cardiometabolic risk factors.

Mean waist circumference declined by 20.5 cm with CagriSema, compared with 4.7 cm with placebo (ETD, −15.8 cm; 95% CI, −16.6 to −15.1; P<.0001). Additional improvements included:

• Fasting plasma glucose: −11.8 mg/dL vs −2.0 mg/dL (ETD, −9.8 mg/dL; P<.0001).
• Insulin resistance (HOMA-IR): −1.9 vs −0.5 (ETD, −1.4; P<.0001).
• Systolic blood pressure: −11.1 mmHg vs −2.0 mmHg (ETD, −9.0 mmHg; P<.0001).
• Diastolic blood pressure: −5.6 mmHg vs −1.3 mmHg (ETD, −4.3 mmHg; P<.0001).

Improvements in all lipid parameters were also greater with CagriSema compared with placebo. At week 68, 33.7% of women receiving CagriSema achieved both a BMI below 27 kg/m² and a waist-to-height ratio below 0.53, compared with 1.9% receiving placebo (P<.0001).²

Safety and Clinical Implications

In the overall REDEFINE 1 trial population, adverse events were primarily gastrointestinal, occurring in 79.6% of participants receiving CagriSema compared with 39.9% receiving placebo. Nausea was reported in 55.0% versus 12.6%, constipation in 30.7% versus 11.6%, and vomiting in 26.1% versus 4.1%, respectively. Most gastrointestinal events were transient and mild to moderate in severity.³

Treatment discontinuation due to adverse events occurred in 5.9% of CagriSema recipients and 3.5% of placebo recipients.

The findings may be particularly relevant for primary care physicians managing obesity during midlife, when menopause-associated hormonal changes can contribute to shifts in body composition, increased abdominal adiposity, and cardiometabolic risk.

However, the analyses were exploratory and conducted post hoc. Menopause status was assigned retrospectively rather than determined through prospective reproductive staging or biochemical confirmation. Additionally, reported outcomes reflect the trial product estimand, which estimates treatment efficacy under an idealized scenario in which participants remained on assigned therapy without additional weight loss treatments.

The data therefore cannot establish whether reproductive stage or HT use influences treatment response, nor do they determine the comparative effectiveness of CagriSema across menopause groups.

Novo Nordisk submitted a new drug application for CagriSema to the FDA in December 2025, with a regulatory decision expected in the fourth quarter of 2026, according to the company's October 20 announcement.³

The investigators concluded that CagriSema produced substantial weight reductions among women with overweight or obesity across menopause stages, including those receiving HT, alongside improvements in abdominal adiposity and cardiometabolic risk factors. Further prospective research is needed to clarify whether menopause-related hormonal changes influence responses to amylin-based and GLP-1–based obesity therapies.

References

1. Hurtado Andrade MD, Hagemann CA, Osorto Contreras CK, 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. Poster P-50. Presented at: The Menopause Society 2026 Annual Meeting; October 20-24, 2026; San Diego, CA.
2. Hurtado Andrade MD, Hagemann CA, Osorto Contreras CK, et al. Effect of CagriSema on body weight reduction and cardiometabolic risk factors in women: a post hoc analysis of the REDEFINE 1 trial. Poster P-51. Presented at: The Menopause Society 2026 Annual Meeting; October 20-24, 2026; San Diego, CA.
3. Novo Nordisk. 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. October 20, 2026. Accessed October 28, 2026. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=918569#
4. 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.