GLP-1 Medications, Menopause, and Cardiometabolic Health

Glucagon‑like peptide‑1 receptor agonists (GLP‑1 RA) are transforming how clinicians approach weight gain, insulin resistance, and cardiovascular risk in midlife women. This is especially important in the menopausal transition, when declining estrogen, visceral weight gain, and shifts in cholesterol and blood sugar markedly increase cardiometabolic risk.​

Why Menopause Raises Cardiometabolic Risk

During the menopausal transition (perimenopause through to postmenopause), falling estradiol is linked to increased central adiposity, insulin resistance, hypertension, and a higher incidence of type 2 diabetes and atherosclerotic cardiovascular disease. Overweight and obesity (BMI ≥25 kg/m²) also raise risk for dyslipidemia, coronary artery disease, and obesity‑related cancers such as breast and endometrial cancer in women.​

"Perimenopause is a critical window for early intervention to mitigate long-term metabolic and cardiovascular risk. However, we are still far away from achieving this based on recent work from the SWAN study showing the prevalence of ideal total Life’s Essential 8 (LE8) scores remained below 25% among midlife women. LE8 is the American Heart Association’s framework for optimal cardiovascular health, including diet, physical activity, nicotine exposure, sleep, weight, blood lipids, blood glucose, and blood pressure."  (El Khoudry, 2025)

How GLP-1 and GLP-1 RA Work

Endogenous GLP‑1 is released from the gut after eating and stimulates insulin secretion, suppresses glucagon, slows gastric emptying, and promotes satiety, thereby improving post‑meal glucose control and reducing appetite. GLP‑1 RA medications mimic these actions, leading to clinically meaningful reductions in blood sugar and body weight while also improving several cardiometabolic markers.​

GLP-1 RA in Menopausal Weight and Metabolic Health

Recent reviews highlight GLP‑1 RA as the most effective pharmacologic option currently available for weight loss, including in peri‑ and postmenopausal women who often struggle with weight gain and “meno‑belly.” Meta‑analyses in menopausal obesity show GLP‑1–based therapies outperform many older agents for achieving ≥5–10% weight loss while also improving waist circumference, blood pressure, and lipids.​

Large cardiovascular outcome trials now extend these benefits beyond glucose and weight. In people with overweight or obesity and established cardiovascular disease but without diabetes, once‑weekly semaglutide reduced major adverse cardiovascular events (MACE: cardiovascular death, non‑fatal myocardial infarction, non‑fatal stroke) by about 20% over roughly three years compared with placebo. This kind of absolute risk reduction is highly relevant for postmenopausal women with elevated BMI and prior cardiovascular events.​

"These drugs promote significant body weight reductions of 20-25% with tirzepatide and around 15% with semaglutide, while improving insulin sensitivity and cardiometabolic markers regardless of reproductive stage. Combining GLP-1s with hormone therapy (HRT) boosts results even further, with postmenopausal women on both achieving up to 19.9% body fat loss versus 15.6% without HRT." (Hurtado, et al., 2024)

Body Composition, Bone Health, and Muscle Loss

Weight loss at midlife is not purely beneficial if too much lean mass and bone density are lost in the process. Muscle and bone mass peak in early adulthood and then progressively decline, with menopause accelerating losses and increasing risk for sarcopenia and osteoporosis. Individuals using GLP‑1 RA may see rapid scale changes that reflect a mix of fat loss and lean mass loss, making resistance training and adequate protein intake non‑negotiable components of any GLP‑1‑supported plan.​

"Women start to accumulate fat in their abdomen during perimenopause, typically around 2 years before menopause. This redistribution of fat, combined with altered lipid metabolism and increased risk for metabolic syndrome occurring during perimenopause, raises the risk of obesity-related conditions even in women whose total body weight remains stable." (El Khouodry, 2025)

Preclinical and clinical data suggest GLP‑1 signalling may have neutral or even favourable effects on bone metabolism, but results are mixed and high‑quality data in postmenopausal women on GLP‑1 RA remain limited. Until more is known, combining GLP‑1 RA with strength training, adequate calcium and vitamin D, and targeted osteoporosis prevention is prudent—especially for women already at increased fracture risk.​

Lifestyle Foundations: Exercise and Nutrition with GLP-1 RA

GLP‑1 RA are most effective when layered onto lifestyle changes rather than replacing them. Regular physical activity improves insulin sensitivity, blood pressure, mood, and sleep while resistance training preserves muscle mass during weight loss. Aim for at least 150 minutes per week of moderate‑intensity aerobic activity plus two to three weekly sessions of resistance training that meaningfully challenge major muscle groups.​

Because GLP‑1 RA suppress appetite and slow gastric emptying, some patients under‑eat, particularly protein. Prioritizing protein at each meal, alongside fiber‑rich carbohydrates and healthy fats, helps maintain lean mass, stabilize blood sugar, and support satiety. Many midlife women benefit from a daily protein target in the range of 1.5–1.6 g/kg body weight (about 0.7 g/lb), adjusted for activity and medical status, distributed across meals.​

Who Should Not Use GLP-1 RA?

GLP‑1 RA are not appropriate for everyone. They require caution or may be contraindicated in people with a history of pancreatitis, significant renal impairment, certain endocrine neoplasias, or specific forms of heart disease, and they frequently cause gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Careful titration, hydration, smaller meals, and close monitoring with a qualified clinician can help manage side effects and determine whether these medications are a good fit within an individualized menopause care plan.​

Interested in learning more? Book a discovery call with Dr. Amy here.

To your best health,

Dr. Amy J. Tung, ND, MSCP

Naturopathic Doctor

Menopause Society Certified Practitioner

References

El Khoudary, Samar R. PhD, MPH. Midlife under pressure: the alarming rise of obesity and insulin resistance among US women. Menopause 32(12):p 1086-1087, December 2025. | DOI: 10.1097/GME.0000000000002702

Huang HW, Ou YC, Lin CY, Lan KC. Management of Obesity in Menopausal Women: Implications for Metabolic Health and Minimally Invasive Surgery. Gynecol Minim Invasive Ther. 2025 Nov 7;14(4):289-296. doi: 10.4103/gmit.GMIT-D-25-00082. PMID: 41262087; PMCID: PMC12626142. 

Hurtado MD, Tama E, Fansa S, Ghusn W, Anazco D, Acosta A, Faubion SS, Shufelt CL. Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use. Menopause. 2024 Apr 1;31(4):266-274. doi: 10.1097/GME.0000000000002310. Epub 2024 Mar 5. PMID: 38446869; PMCID: PMC11209769.

Mikdachi H, Dunsmoor-Su R. GLP-1 receptor agonists for weight loss for perimenopausal and postmenopausal women: current evidence. Curr Opin Obstet Gynecol. 2025 Apr 1;37(2):97-101. doi: 10.1097/GCO.0000000000001015. Epub 2025 Feb 25. PMID: 39970049.

Odigwe C, Mulyala R, Malik H, Ruiz B, Riad M, Sayiadeh MA, Honganur S, Parks A, Rahman MU, Lakkis N. Emerging role of GLP-1 agonists in cardio-metabolic therapy - Focus on Semaglutide. Am Heart J Plus. 2025 Mar 1;52:100518. doi: 10.1016/j.ahjo.2025.100518. PMID: 40115122; PMCID: PMC11923757.

Xie B, Chen S, Xu Y, Han W, Hu R, Chen M, Zhang Y, Ding S. The Impact of Glucagon-Like Peptide 1 Receptor Agonists on Bone Metabolism and Its Possible Mechanisms in Osteoporosis Treatment. Front Pharmacol. 2021 Jun 14;12:697442. doi: 10.3389/fphar.2021.697442. PMID: 34220521; PMCID: PMC8243369.

Disclaimer:

The information in this blog is for educational and informational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the guidance of your doctor or other qualified health professional with any questions regarding a medical condition or treatment. Never disregard professional medical advice or delay seeking treatment because of something you have read in this blog.

Individual results may vary, and the strategies discussed here are not guaranteed to work for everyone. This content does not create a patient-client relationship and should not be used as a replacement for personalized medical care.