By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
What’s new about CagriSema in menopause?
CagriSema in menopause now has its first encouraging data. A new analysis of a large trial showed that women who received the injection lost an average of 25.0% of their body weight. The weight loss stayed large before menopause, during the transition and after it. The researchers presented the data in October at the annual meeting of The Menopause Society, the North American menopause organization, in San Diego.
Why does weight go up in midlife?
Many women know the feeling. Their diet has not changed, their activity is similar, but the scale keeps climbing. In addition, fat gradually shifts from the hips to the belly. According to a Mayo Clinic review, age, the drop in estrogen after menopause and other factors drive these changes.
Belly fat is not just a matter of appearance. It raises the risk of high blood sugar, abnormal blood fats, high blood pressure and heart disease. That is why effective treatment matters so much in these years. I covered this in more depth in my guide to obesity treatment during menopause.
What is CagriSema and how does it work?
CagriSema is an investigational weekly injection from Novo Nordisk. It combines two drugs. The first is semaglutide, the active ingredient in Wegovy. The second is cagrilintide, a drug that mimics the hormone amylin.
Semaglutide acts on the receptor for GLP-1, a gut hormone that signals fullness to the brain. Amylin, on the other hand, is a hormone that the pancreas releases together with insulin after a meal. It also calms hunger, but through a different pathway in the brain. In this way, the two signals complement each other. If you want to go deeper, I wrote about how amylin works.
What did the REDEFINE 1 trial examine?
The REDEFINE 1 trial lasted 68 weeks. It included 3,417 adults with obesity or overweight who did not have diabetes. All of them had a body mass index (BMI) of 30 or higher, or 27 or higher with at least one obesity-related complication. The researchers randomly assigned them to four groups: CagriSema, semaglutide alone, cagrilintide alone or placebo, meaning a dummy injection. All participants also received lifestyle support.
In the official results, which appeared in NEJM, participants in the CagriSema group lost an average of 20.4% of their weight, compared with 3.0% in the placebo group. About two-thirds of the participants were women, and the new analysis of CagriSema in menopause focuses on them. I reviewed the entire program in my guide to all the REDEFINE trials.
Results in all women
The first analysis included all 2,309 women in the trial. After 68 weeks, women on CagriSema lost an average of 25.0% of their weight. With semaglutide alone, the loss was 19.0%, and with cagrilintide alone, 13.4%. In the placebo group, the loss was only 3.0%. In other words, the combination led to much greater weight loss than either drug on its own. This is important background for understanding the data on CagriSema in menopause.
Waist circumference, a simple measure of belly fat, also improved. With CagriSema it fell by 20.5 cm, compared with 4.7 cm on placebo. Put simply, of every 100 women on CagriSema, about 93 lost at least 10% of their weight (93.3%), and about 69 lost at least 20% (68.7%). By contrast, in the placebo group, only about 13 in 100 reached 10% (12.7%), and fewer than two reached 20% (1.8%).
CagriSema in menopause: results by stage
The second analysis divided 1,902 women who received CagriSema or placebo by menopause stage. Before menopause, the average loss with CagriSema was 26.7%, compared with 2.1% on placebo. During the transition itself, known as perimenopause, women lost 24.8%, compared with 1.7%. After menopause, in postmenopause, the loss was 23.1%, compared with 2.6%.
The researchers also looked separately at women on hormone therapy. According to a report from the meeting, they lost an average of 25.6%. The lead investigator, Dr. Maria Hurtado Andrade of the Mayo Clinic, called the results encouraging. In her view, women after menopause may lose a little less, but the weight loss is still medically meaningful.
What the data on CagriSema in menopause do not tell us
This is a post hoc analysis, meaning the researchers ran it after the trial ended. The researchers did not design the trial in advance to answer this question. That is why the company itself describes the findings as hypothesis-generating only.
In addition, the researchers determined menopause stage by age, medical history and symptoms, rather than by hormone tests. Moreover, the numbers describe an ideal scenario in which all participants stayed on treatment. For this reason, they are higher than the trial’s official result, and you cannot compare the two directly. Finally, the researchers did not run a statistical test to check whether the differences between stages are real.
Side effects: what you should know
The most common side effects were digestive. Across the whole trial, they occurred in 79.6% of patients on CagriSema, compared with 39.9% on placebo. Most of them went away, and they were mild to moderate. Nausea occurred in 55% (vs. 12.6%), constipation in 30.7% (vs. 11.6%) and vomiting in 26.1% (vs. 4.1%). Overall, 5.9% stopped treatment because of side effects, compared with 3.5% on placebo. These figures come from the whole trial, not from a separate analysis of CagriSema in menopause.
The lead investigator recommends a follow-up visit 4 to 6 weeks after starting treatment, as well as follow-up after each dose increase. If side effects are severe, the dose can go up more slowly. Simple habits also help: small meals, eating slowly, stopping when you feel full and drinking enough fluids. You can read more in my article on GLP-1 side effects.
Protecting muscle and bone with CagriSema in menopause
Fast, large weight loss calls for attention to muscle and bone. This is especially true after menopause, when the risk of losing muscle and bone mass is already high. So the lead investigator stresses three things: enough protein, strength training and the right nutritional support.
At our clinic, the dietitian builds a personal protein plan with each patient. I also recommend starting strength training right at the beginning of treatment. I gathered six practical steps in my guide to preventing muscle loss during weight loss.
When will CagriSema be available?
Novo Nordisk submitted an application for approval to the U.S. Food and Drug Administration (FDA) in December 2025. The agency’s decision is due in the last quarter of 2026. For now, the drug does not have approval in the United States. In Israel, it will also need separate registration with the Ministry of Health. In the meantime, it is worth following the head-to-head comparison with Mounjaro in the REDEFINE 4 trial.
The bottom line on CagriSema in menopause
The new data are encouraging. Women at every stage of menopause lost an average of about a quarter of their body weight with CagriSema, and their waistlines shrank noticeably. Still, this is a post hoc analysis, and the drug is still awaiting approval. Until then, effective treatments for women in these years already exist today. The foundation is the right medication, enough protein, strength training and good sleep.
The information in this article is general and is not personal medical advice. It is best to make any treatment decision together with your doctor.
References
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity
CagriSema Tied to 25% Weight Loss in Women, Post Hoc Data Show
CagriSema Reduces Weight in Women Across Menopause Stages, HT Use
Novo Nordisk funded the REDEFINE 1 trial and the analyses presented at the meeting.
