Novo today reported findings from two post hoc analyses of the REDEFINE 1 trial, a phase 3 study in adults with obesity or overweight, presented at The Menopause Society 2026 Annual Meeting in San Diego.
In the first analysis of 2,309 women, the investigational once-weekly combination CagriSema 2.4 mg / 2.4 mg was associated with an average weight loss of 25.0% at week 68 versus 3.0% with placebo, based on the efficacy estimand (estimated efficacy in an idealized scenario in which all patients remained on treatment and took no other weight loss therapies).
A second analysis of 1,902 women with overweight or obesity, grouped post hoc by menopausal status, showed average weight loss at week 68 of 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% with placebo, respectively.
CagriSema is an investigational once-weekly combination of semaglutide 2.4 mg, a GLP-1 receptor agonist, and cagrilintide 2.4 mg, a long-acting amylin analog.
If approved, it has the potential to be the first amylin analog and GLP-1 RA combination therapy for weight management.
Why Menopausal Stage Matters in Obesity
Women undergo major hormonal shifts across the different stages of menopause, which can drive increased abdominal fat accumulation and affect body composition, body weight and cardiometabolic risk.
More than 86 million women in the U.S.
are aged 40 and older—the years during which perimenopause, menopause and postmenopause occur—yet reproductive stage is rarely evaluated as a factor in obesity research.
Weight Loss and Waist Circumference Across All Women
In the analysis of all 2,309 women enrolled in REDEFINE 1, 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, along with meaningful improvements in waist circumference—a secondary endpoint of REDEFINE 1 and a measure associated with abdominal fat.
The table below summarizes bodyweight change and waist circumference outcomes at week 68 (efficacy estimand):.
| 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 cma | –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.
Results by Menopausal Stage
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.
| 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% |
| 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.
Expert Commentary
“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.”.
“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.”.
Safety Profile
In the REDEFINE 1 trial, discontinuation due to adverse events occurred in 5.9% of participants receiving CagriSema versus 3.5% with placebo.
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%) and vomiting (26.1% vs 4.1%), and were mostly transient and mild-to-moderate in severity.
Regulatory Status and Next Steps
These 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, with a decision expected in Q4 2026.
CagriSema is not approved for use in the United States, and its safety and efficacy are not established.
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