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

Rashad Iskandrni 

•      Investigational CagriSema 2.4 mg / 2.4 mg showed significant weight loss among women overall and across pre-, peri- and postmenopausal stages in two post hoc analyses from REDEFINE 1, a phase 3 trial in adults with obesity or overweight¹,²

•      Across the two analyses, CagriSema use was associated with reductions in abdominal fat, as measured by waist circumference, among women overall and across menopause stages¹,²

•      CagriSema is an investigational once-weekly combination of semaglutide, a GLP-1 receptor agonist (RA), and cagrilintide, a long-acting amylin analog

Today, Novo announced results from two post hoc analyses of the REDEFINE 1 trial presented at The Menopause Society 2026 Annual Meeting in San Diego. In an analysis of 2,309 women with obesity or overweight, CagriSema 2.4 mg / 2.4 mg (cagrilintide 2.4 mg and semaglutide 2.4 mg) was associated with an average weight loss of 25.0% at week 68, compared with 3.0% with placebo, if all patients adhered to treatment (efficacy estimand*).1 In a second analysis of 1,902 women with overweight or obesity assigned post hoc by menopausal status, average weight loss at week 68 was 26.7%, 24.8% and 23.1% in premenopausal, perimenopausal and postmenopausal women, compared with 2.1%, 1.7% and 2.6% with placebo, respectively (efficacy estimand*).2

 “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,” said Michelle Skinner Moore, PharmD, MBA, interim head of clinical development, medical and regulatory affairs and vice president, medical affairs at Novo. “CagriSema has the potential to be the first amylin analog and GLP-1 RA combination therapy for weight management, and these REDEFINE 1 data show it was associated with significant weight loss for women with obesity or overweight. These findings add to the body of evidence from the REDEFINE clinical program.”

Women experience major hormonal shifts throughout the different stages of menopause, which can increase abdominal fat accumulation and impact body composition, weight and cardiometabolic risk.2,3 More than 86 million women in the U.S. are aged 40 and older, the years in which perimenopause, menopause and postmenopause occur,4 yet reproductive stage is rarely evaluated as a factor in obesity research.5

In the post hoc analysis of all 2,309 women enrolled in the REDEFINE 1 trial, treatment with CagriSema 2.4 mg / 2.4 mg was associated with an average weight loss of 25.0% at week 68, compared with 3.0% with placebo, as well as meaningful improvements in waist circumference – a secondary endpoint of the REDEFINE 1 trial and a measure associated with abdominal fat.1

Change in bodyweight and waist circumference, and achievement of weight-loss targets, among women in REDEFINE 1 at week 68, efficacy estimand results*1

Outcome at week 68      CagriSema

2.4 mg / 2.4 mg (n=1,441)         Semaglutide

2.4 mg

(n=199)      Cagrilintide

2.4 mg

(n=208)      Placebo (n=461)

Baseline bodyweight, mean      101.5 kg         100.2 kg     101.4 kg     102.2 kg

Change in bodyweight   –25.0% a    –19.0%        –13.4%      –3.0%

Change in waist circumference –20.5 cm a       –17.4 cm    –11.7 cm    –4.7 cm

Achieved ≥10% bodyweight loss         93.3% a      82.2%        62.0%         12.7%

Achieved ≥20% bodyweight loss         68.7% a      38.0%        17.9%         1.8%

a Statistically significant compared with placebo, estimated mean, p<0.0001; p values were not adjusted for multiplicity and formal treatment-by-sex interaction testing was not performed

In a separate post hoc analysis, 1,902 women with overweight or obesity in REDEFINE 1 who received CagriSema 2.4 mg / 2.4 mg or placebo were evaluated by menopausal stage. Menopause status was derived post hoc using age, medical history, and recorded symptoms and was not based on prospectively collected reproductive staging or biochemical confirmation. CagriSema was associated with clinically meaningful weight loss across all menopause stages, with an average weight loss at week 68 of 26.7% in premenopausal women, 24.8% in perimenopausal women and 23.1% in postmenopausal women.2 

Change in bodyweight from baseline to week 68, efficacy estimand results*2

Post hoc analysis group by menopause status (CagriSema n / placebo n)         CagriSema 2.4 mg / 2.4 mg (change from baseline)      Placebo (change from baseline)

Premenopausal (408 / 122; baseline 104.3 / 107.1 kg) –26.7% a    –2.1%

Post hoc analysis group by menopause status (CagriSema n / placebo n)         CagriSema 2.4 mg / 2.4 mg (change from baseline)      Placebo (change from baseline)

Perimenopausal (256 / 81; baseline 102.7 / 99.6 kg)      –24.8% a    –1.7%

Postmenopausal (530 / 168; baseline

99.1 / 99.3 kg)      –23.1% a    –2.6%

a Statistically significant compared with placebo, estimated mean, p<0.0001; p values were not adjusted for multiplicity and formal treatment-by-subgroup interaction testing was not performed

 “This post hoc analysis from REDEFINE 1 offers new insight into weight loss with investigational

CagriSema in women grouped by reproductive life stage,” said Maria D. Hurtado Andrade, M.D., Ph.D., Assistant Professor, Mayo Clinic Alix School of Medicine, and lead author of the analyses. “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.”

In the REDEFINE 1 trial, discontinuation due to adverse events occurred in 5.9% of participants receiving CagriSema versus 3.5% with placebo.6 Adverse events were mainly gastrointestinal (79.6% in the CagriSema group vs 39.9% with placebo) including nausea (55% vs 12.6%), constipation (30.7% vs 11.6%), vomiting (26.1% vs 4.1%) and were mostly transient and mild-tomoderate in severity.6

Exploratory post hoc analyses are hypothesis-generating, and further work investigating the clinical validity of these results would be of value.

Novo filed a New Drug Application with the U.S. Food and Drug Administration in December 2025 for CagriSema for weight management. A decision is expected in Q4 2026. CagriSema is not approved for use in the United States. Safety and efficacy are not established.

*Based on the efficacy estimand: estimated efficacy in an idealized scenario in which all patients stayed on treatment and took no other weight loss therapies.