CagriSema Linked to Greater Weight Loss in Women Across Reproductive Stages

Key takeaways:

• Women who received CagriSema in REDEFINE 1 lost 25% of their body weight at 68 weeks.
• Premenopausal women treated with CagriSema showed the greatest weight loss compared with perimenopausal and postmenopausal women.

Once-weekly CagriSema produced a 25% weight reduction at 68 weeks in women with overweight or obesity, with benefits seen across all reproductive stages, according to data presented in two posters.

In earlier reporting, adults in the REDEFINE 1 trial who received a weekly combination of cagrilintide 2.4 mg and semaglutide 2.4 mg (Novo Nordisk) lost 20.4% of their body weight at 68 weeks, compared with 3% for placebo, based on the treatment policy estimand. In post hoc analyses shared at The Annual Meeting of The Menopause Society, investigators looked at how CagriSema affected body weight and cardiometabolic health in women.

“Women go through major shifts in body composition across their lives, driven by hormonal changes and aging,” Maria D. Hurtado Andrade, MD, PhD, assistant professor of medicine at Mayo Clinic Alix School of Medicine, told Healio. “The menopause transition, in particular, is associated with fat mass gain and its redistribution toward the abdomen, which increases cardiovascular risk. Despite this, we know relatively little about whether obesity medications work differently across reproductive life stages. Looking at women separately, and then by premenopause, perimenopause, postmenopause, and hormone therapy use, helps us understand whether these treatments meet the needs of women at every stage of life.”

Weight change among women

For the first post hoc analysis, researchers evaluated 2,309 women with overweight or obesity who did not have type 2 diabetes. Participants were assigned in a 21:3:3:7 ratio to once-weekly CagriSema 2.4 mg/2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg or placebo for 68 weeks.

Using the trial product estimand, women treated with CagriSema lost 25% of their body weight at 68 weeks, compared with 19% with semaglutide alone, 13.4% with cagrilintide alone and 3% with placebo. The CagriSema group also had a larger reduction in waist circumference than the other three groups. The share of women who lost at least 20% of body weight was 68.7% with CagriSema, 38% with semaglutide, 17.9% with cagrilintide and 1.8% with placebo.

CagriSema also led to greater improvements in systolic blood pressure and LDL cholesterol than the other three treatments at 68 weeks. HDL cholesterol rose more with CagriSema than with semaglutide alone or placebo. Compared with cagrilintide alone and placebo, CagriSema produced larger improvements in diastolic blood pressure, fasting plasma glucose and triglycerides.

At 68 weeks, 33.7% of women in the CagriSema group achieved a BMI below 27 kg/m² and a waist-to-height ratio below 0.53, compared with 1.9% in the placebo group.

Weight loss during reproductive stages

In the second post hoc analysis, researchers examined weight loss in 1,902 women randomly assigned to CagriSema 2.4 mg/2.4 mg or placebo in REDEFINE 1. Body weight, waist circumference and cardiometabolic risk factors were assessed in four groups: premenopausal women, perimenopausal women, postmenopausal women and women using hormone therapy.

According to the trial product estimand, women receiving CagriSema lost more weight than those receiving placebo in premenopause (estimated treatment difference, –24.6 percentage points; 95% CI, –26.5 to –22.8), perimenopause (estimated treatment difference, –23.1 percentage points; 95% CI, –25.4 to –20.8), postmenopause (estimated treatment difference, –20.5 percentage points; 95% CI, –22.1 to –18.9) and among hormone therapy users (estimated treatment difference, –23.3 percentage points; 95% CI, –25.3 to –21.2). Waist circumference also fell more with CagriSema than with placebo across all reproductive stages and among hormone therapy users. A greater proportion of women treated with CagriSema achieved at least 10% and at least 20% weight loss than those given placebo across all groups.

“We observed a tendency toward greater weight loss in premenopausal women, including a higher proportion achieving at least 20% weight reduction compared with the other groups,” Hurtado Andrade said. “These are numerical differences from a post hoc analysis without formal statistical testing, so we interpret them cautiously. Still, they raise interesting questions about whether reproductive aging influences response to treatment.”

Across all three reproductive stages, CagriSema produced greater improvements in blood pressure, fasting plasma glucose, HDL cholesterol and triglycerides. It lowered LDL cholesterol more in premenopausal and perimenopausal women, but not in postmenopausal women. Among hormone therapy users, CagriSema improved blood pressure, fasting plasma glucose and triglycerides more than placebo, while HDL and LDL cholesterol were similar between groups at 68 weeks.

“These findings suggest that, if approved, CagriSema could be an effective option for women with overweight or obesity regardless of where they are in their reproductive life,” Hurtado Andrade said. “That includes the menopause transition when many women find weight management especially challenging. The improvements in central adiposity, blood pressure, fasting glucose and triglycerides are clinically important, because these factors drive cardiometabolic risk in midlife and beyond.”

Hurtado Andrade said additional prospective studies are needed to assess obesity treatments across the reproductive lifespan. She added that future work should classify women by reproductive stage using biochemical or clinical data rather than age alone.

“It will also be important to understand the biological mechanisms behind any differences in response, such as changes in sex hormones, body composition and fat distribution,” Hurtado Andrade said. “We also need to know how HT formulation and timing interact with treatment.”

For more information:

Maria D. Hurtado Andrade, MD, PhD, is an assistant professor of medicine at the Mayo Clinic Alix School of Medicine; in the division of endocrinology, diabetes and metabolism, department of medicine at Mayo Clinic in Jacksonville, Florida; and in the precision medicine for obesity program at Mayo Clinic in Rochester, Minnesota. Hurtado Andrade can be reached at [email protected].

Sources/Disclosures

Source:

Hurtado Andrade MD, et al. P-51. Presented at: The Annual Meeting of The Menopause Society; San Diego.

Reference:

• Hurtado Andrade MD, et al. P-50. Presented at: The Annual Meeting of The Menopause Society; San Diego.

Disclosures: Hurtado Andrade reports consulting for Verge Genomics; receiving honoraria and meeting or travel support from The Menopause Society and Novo; advising for Boehringer Ingelheim, F. Hoffmann-La Roche, Novo and Viking Therapeutics; and receiving research support paid to Mayo Clinic from Endogenex, the Mayo Clinic Women's Health Research Center and Phenomix Sciences. The trial was sponsored by Novo.