Semaglutide and weight loss in menopause

By Dr. Liji Thomas, MDReviewed by Lily Ramsey, LLM

What is Semaglutide and how does it work?
Clinical evidence: Semaglutide for weight loss in menopausal women
Potential benefits for women in menopause
Risks and considerations
How Semaglutide fits into a comprehensive weight management plan
The future of GLP-1 therapies for weight management in menopause

Unwanted weight gain occurs in 70% of women post-menopause. Menopause is associated with low ovarian but increased peripheral estrogens and a relative rise in androgen levels.³

The result is reduced muscle protein mass and bone density, coupled with increased abdominal fat mass. This leads to insulin resistance, a lower basal metabolic rate (BMR) – the rate at which the body uses up calories at rest – and weight gain.¹¹

Loss of muscle protein increases the appetite for protein via muscle/liver hormones. However, if the extra food consumed is not protein-rich, excessive calories are added, contributing to weight gain.¹²

Aging, menopausal symptoms, and hormone shifts act together to discourage physical activity, increase food intake, and reduce sleep, which also promotes poor food habits, including excessive snacking.^1,3

Genetic factors and medications may also cause weight gain.³ Women from families that run to increased belly fat are at greater risk, hinting at the role of genetic factors.¹

Semaglutide and weight loss in menopause" />Image Credit: MillaF/Shutterstock.com

What is Semaglutide and how does it work?

Glucagon-like peptide-1 (GLP-1) is an incretin, a metabolic hormone that stimulates insulin secretion in a blood-sugar-dependent manner after eating. Semaglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist that mimics GLP-1 actions.⁶

Semaglutide not only reduces blood sugar levels but also restores insulin sensitivity, probably by weight loss. It reduces appetite by producing feelings of fullness. It decreases total energy intake by reducing cravings for energy-dense, highly palatable foods.^5,9

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Clinical evidence: Semaglutide for weight loss in menopausal women

Multiple trials, including hundreds of obese/overweight women in the menopausal/postmenopausal age group, reflect weight loss of at least 5% with three months of semaglutide treatment.^13-15

This is comparable to that seen in premenopausal women despite higher initial body weight and fat mass in postmenopausal women.^4,6,13

Concurrent hormone replacement therapy (HRT) potentiates this effect by restoring the protective estrogenic milieu.³ Coupled with the metabolic benefits of this drug, the Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT) trial showed a 20% reduction in major cardiovascular events with Semaglutide, making it the only weight loss medication to do so.²

Side effects of Semaglutide include mostly nausea, vomiting, diarrhea, or constipation, which can cause discontinuation.¹⁶ Other less common potential adverse effects include gallbladder disease, pancreatitis and pancreatic cancer, thyroid cancer, acute kidney injury, and worsening of diabetic retinopathy (DRP). However, these risks may be due to the presence of obesity, long-term diabetes, and the use of other drugs.¹⁶

Potential benefits for women in menopause

Semaglutide could help postmenopausal women lose weight, restore insulin sensitivity, and achieve blood sugar control. Semaglutide regulates food intake through appetite regulation.¹⁷

Menopause increases the risk of cardiometabolic diseases like type 2 diabetes mellitus (T2DM), high cholesterol levels, fatty liver, and cardiovascular disease (CVD), the latter being the leading killer among women.² Semaglutide could ameliorate these risks.¹¹

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Risks and considerations

"Compared with placebo and active comparator, semaglutide induces mostly mild and transient gastrointestinal disturbances and increases the risk of cholelithiasis."¹⁶

It does not alter the levels of commonly used medications like HRT, metformin, or diuretics.^5,7 It is safe in patients with hepatic and renal impairment and is considered to be well-tolerated.¹²

It is contraindicated in women with acute pancreatitis, congestive heart failure, medullary thyroid carcinoma and multiple endocrine neoplasia syndrome type 2 (MEN 2).¹²

How Semaglutide fits into a comprehensive weight management plan

It is important to integrate Semaglutide into a well-rounded weight management lifestyle plan to keep weight off even after stopping the drug. Increased moderate physical activity for 150-200 minutes a week is helpful in building muscle mass and promoting healthy sleep. Healthy nutrition is key, with calorie restriction as required to create an energy deficit.^1,11

Semaglutide increases weight loss when incorporated into such a plan, especially when combined with HRT, which potentiates its weight loss effects.⁵ The risks should be considered in making such decisions.

How Does Semaglutide Work to Lose Weight?

The future of GLP-1 therapies for weight management in menopause

Semaglutide and other GLP-1 receptor agonists are being investigated for extended applications, including non-alcoholic steatohepatitis (NASH) and neurodegenerative disease. The latter include Parkinson’s disease and Alzheimer’s disease, both of which are disabling illnesses. AD targets more women than men.⁸

The neuroprotective effects of these drugs, including Semaglutide, have been demonstrated in animal and human studies.⁹

Future drug developments targeting menopausal weight gain include other oral and injectable GLP-1 agonists, orforglipron and danuglipron, ecnoglutide and mazdutide; APHD-012 that mimics gastric bypass surgery for weight loss but is taken once daily to selectively stimulate the small intestine and induce feelings of fullness, reducing food intake; and ARD-101, which reduces hunger by stimulating bitter taste receptors in the mouth.¹⁸

Additionally, trials are going on for oral amycretin has both GLP-1 agonist function and stimulates amyline, inducing satiety after eating and helping reduce weight; CagriSema (a combination of cagrilintide and Semaglutide); the small molecule oral cannabinoid receptor 1 (CB1) inverse agonist, Monlunabant; and triple agonist retatrutide.¹⁸

References

1. The reality of menopause weight gain. Available at: https://www.mayoclinic.org/healthy-lifestyle/womens-health/in-depth/menopause-weight-gain/art-20046058. Accessed on February 21, 2025.
2. Hurtado, M. D., Tama, E., Fansa, S., et al. (2024). Weight Loss Response to Semaglutide in Post-menopausal Women with and without Hormone Therapy Use. Menopause. doi: https://doi.org/10.1097/GME.0000000000002310.
3. Knight, M. G., Anekwe, C., Washington, K., et al. (2021). Weight Regulation in Menopause. Menopause. doi: https://doi.org/10.1097/GME.0000000000001792.
4. Nicolau, J., Blanco-Anesto, J., Bonet, A., et al. (2025). Effectiveness of Low Doses of Semaglutide on Weight Loss and Body Composition Among Women in Their Menopause. Metabolic Syndrome and Related Disorders. doi: https://doi.org/10.1089/met.2024.0124.
5. Jordy, A. B., Albayaty, M., Breitschaft, A., et al. (2021). Effect of Oral Semaglutide on the Pharmacokinetics of Levonorgestrel and Ethinylestradiol in Healthy Postmenopausal Women and Furosemide and Rosuvastatin in Healthy Subjects. Clinical Pharmacokinetics. doi: https://doi.org/10.1007/s40262-020-00976-x.
6. Davies, M., Pieber, T. R., Hartoft-Nielsen, M., et al. (2017). Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes. JAMA Network. doi: https://doi.org/10.1001/jama.2017.14752.
7. Baekdal, T. A., Borregard, J., Hansen, C. W., et al. (2019). Effect of Oral Semaglutide on the Pharmacokinetics of Lisinopril, Warfarin, Digoxin, and Metformin in Healthy Subjects. Clinical Pharmacokinetics. doi: https://doi.org/10.1007/s40262-019-00756-2.
8. Mahapatra, M. K., Karuppasamy, M., & Sahoo, B., M., et al. (2022). Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review. Pharmaceutical Research. doi: https://doi.org/10.1007/s11095-022-03302-1.
9. Van Bloemendaal, L., ten Kulve, J. S., la Fleur, S. E., et al. (2014). Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. Journal of Endocrinology. doi: https://doi.org/10.1530/JOE-13-0414.
10. Genazzani, A. D., Petrillo, T., Semprini, E., et al. (2023). Metabolic syndrome, insulin resistance and menopause: the changes in body structure and the therapeutic approach. GREM. doi: https://doi.org/10.53260/grem.234026.
11. Kommu, S., Whitfield, P. Semaglutide. [Updated 2024 Feb 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK603723/. Accessed on February 24, 2025.
12. Simpson, S. J., Raubenheimer, D., Black, K. I., et al. (2022). British journal of obstetrics and gynecology. doi: https://doi.org/10.1111/1471-0528.17290.
13. Ghusn, W., De la Rosa, A., Sacoto, D., et al. (2022). Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity. Nutrition, Obesity, and Exercise. doi:10.1001/jamanetworkopen.2022.31982.
14. Rubino, D. M., Greenway, F. L., Khalid, U., et al. (2022). Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. doi:10.1001/jama.2021.23619.
15. Vosoughi, K., Atieh, J., Khanna, L., et al. (2021). Association of glucagon-like peptide 1 analogs and agonists administered for obesity with weight loss and adverse events: a systematic review and network meta-analysis. The Lancet. doi: https://doi.org/10.1016/j.eclinm.2021.101213.
16. Smits, M. M., and Van Raalte, D. H. (2021). Safety of Semaglutide. Frontiers in Endocrinology. doi: https://doi.org/10.3389/fendo.2021.645563.
17. Blundell, J., Finlayson, G., Axelsen, M., et al. (2017). Effects of once‐weekly Semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes, Obesity, and Metabolism. doi: https://doi.org/10.1111/dom.12932.
18. Murdock, J. (2024). The Latest Updates: 16 New Weight Loss Drugs on the Horizon. Available at: https://www.goodrx.com/conditions/weight-loss/new-weight-loss-drugs. Accessed on March 4, 2025.

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