Glucagon-like peptide-1 (GLP-1) agonists for weight loss have exploded in popularity in recent years, with as many as one in eight adults reporting having used one at some point in their lives. There has been uncertainty around the efficacy of these medications for women in the perimenopausal or postmenopausal stages of their lives, a time when weight gain is common — especially around the midsection. A post-hoc analysis led by endocrinologists at NewYork-Presbyterian and Weill Cornell Medicine, however, shows that GLP-1 agonist tirzepatide is equally effective throughout all reproductive stages of a woman's life.
The findings are likely to be applicable to other GLP-1 agonists and offer reassurance to physicians interested in prescribing these medications for their patients who are in or nearing menopause. Beverly Tchang, M.D., an endocrinologist at NewYork-Presbyterian and Weill Cornell Medicine and a researcher specializing in obesity medicine, was the primary author of the study, which was recently published in Obesity. Below, she describes the goals of the study, the findings, and how they can help support patient care.
We wanted to know if weight-loss medications are just as effective during menopause as they are during other reproductive stages of life. Do they only work well for women who haven’t yet entered the menopausal transition?
— Dr. Beverly Tchang
Research Background
One of the primary concerns for women in menopause is weight gain. Patients often report gaining weight or holding on to weight more than they did before menopause. Research has shown that, during the menopausal transition, there is a redistribution of fat mass from the hips to the abdomen. Estrogen deficiency affects lipid metabolism and can increase cardiometabolic risk. People who carry more weight around the middle have an increased risk of metabolic problems, such as type 2 diabetes, hypercholesterolemia, and hypertension.
As physicians and researchers, we wanted to know if weight-loss medications are just as effective during menopause as they are during other reproductive stages of life. Do they only work well for women who haven’t yet entered the menopausal transition? Are they less effective in women who have hormonal imbalances predisposing them to weight gain and who are holding onto weight as part of menopause? Those were the primary questions we sought to explore in our analysis.
Research Methods
We performed a secondary analysis of participants in SURMOUNT, a global phase 3 multicenter program comprised of four clinical trials looking at the safety and efficacy of tirzepatide. Results from the SURMOUNT trials showed that tirzepatide was effective for weight reduction as well as improvements in cardiometabolic parameters. However, it was unknown whether a woman’s reproductive stage impacts her body weight reductions and cardiometabolic improvements.
Our post hoc analysis included 2,542 women from the SURMOUNT-1, SURMOUNT-3, and SURMOUNT-4 clinical trials. In those trials, the participants were randomized to receive tirzepatide (15 mg or maximum tolerated dose) or a placebo, and they were followed for up to 88 weeks. We retrospectively categorized participants as being in the premenopausal (younger than 45), perimenopausal (40 to 54 years), or postmenopausal (older than 40 with documented menopause or bilateral oophorectomy) stages of life. We compared body weight and waist circumference changes, including changes in waist-to-height ratio, by reproductive stage.
Key Findings
In all three trials, we found that tirzepatide was associated with significant reductions in body weight, waist circumference, and waist-to-height ratio versus placebo in women living with obesity or overweight, regardless of their reproductive stage. In SURMOUNT-1, for example, significantly greater body weight reductions from baseline were observed with tirzepatide versus placebo in women in the premenopausal (26% vs. 2%), perimenopausal (23% vs. 3%), and postmenopausal (23% vs. 3%) stages.
Clinicians prescribing tirzepatide can feel more confident recommending this medication to their patients, especially women reporting menopause-related weight gain.
— Dr. Beverly Tchang
The reduction in waist circumference for the tirzepatide versus placebo groups followed a similar trend for each subgroup: 22 cm vs. 4 cm, 20 cm vs. 5 cm, and 20 cm vs. 4 cm, respectively. Furthermore, 30% to 52% of women across the reproductive stage subgroups who had a body mass index (BMI) under 35 reached a waist-to-height ratio of 0.49 or less with tirzepatide, which is within the optimal range for good cardiometabolic health.
We observed similar results for participants in the SURMOUNT-3 and SURMOUNT-4 clinical trials.
Clinical Implications
Our study confirms that tirzepatide, in combination with lifestyle changes, works well regardless of a woman's decade of life. Whether she is premenopausal, perimenopausal, or postmenopausal, the medication results in an approximately 20% weight reduction. Because the majority of participants in clinical trials of other drugs in this class were women in their 50s, it is likely that the findings may be applied to other GLP-1 agonists.
It's worth taking a moment to talk about waist-to-height ratio. There has been discussion of the validity of BMI as an endpoint in obesity research, since some people with low muscle mass can have a lower BMI but still be unhealthy. Obesity medicine researchers prefer waist-to-height ratio to BMI because it provides us with a more direct measure of where a person is carrying their weight. Because carrying weight around the abdomen is associated with an increased risk of cardiometabolic disease, we were gratified to see the benefits of tirzepatide for reducing the waist-to-height ratio.
Based on our research, we believe clinicians prescribing tirzepatide can feel more confident recommending the medication to their patients, especially women reporting menopause-related weight gain. The data provides reassurance that this medication is effective in the setting of perimenopause and menopause.
