What is the relationship between GLP-1 drugs and polycystic ovarian syndrome (PCOS)?

Rebecca Jaspan, MPH, RD, CEDS, CDCES

Everywhere you turn these days, it seems as if someone is talking about Ozempic, Wegovy, or Mounjaro, diabetes drugs more recently advertised as weight loss medications. More recent research is pointing to the use of this class of drugs called Glucagon-like peptide 1 (GLP-1) receptor agonists in polycystic ovarian syndrome (PCOS).  How do these medications work for people with PCOS and what are possible risks or concerns?  Here’s what to know about GLP-1 receptor agonists and PCOS.

How Do GLP-1 Receptor Agonists Impact PCOS?

These drugs are effective for individuals with diabetes and insulin resistance because they mimic the action of glucagon-like peptide 1, a signaling hormone that helps to lower blood sugar levels.  There are three primary ways that GLP-1s help manage blood sugar:

• They delay stomach emptying. After a meal, digestion is slowed so that nutrients are released more slowly into the bloodstream, preventing a blood sugar spike.
• They improve insulin resistance of adipose tissue, though the mechanism is unclear.¹
• They decrease the sugar stored in the liver that gets released into your bloodstream.

While not yet approved by the FDA for PCOS, GLP-1s are being explored for use in its treatment.  An estimated 5 million women in the United States are diagnosed with PCOS, which is a condition that causes women to have insulin resistance, produce excess testosterone and can come with symptoms that include irregular periods, infertility, facial and body hair, severe acne, and ovarian cysts.  These hormonal imbalances can also contribute to metabolic issues such as high cholesterol and triglycerides.²  GLP-1s are thought to help with these PCOS symptoms by lowering fasting blood sugar, improve insulin sensitivity, and lowering cholesterol and triglycerides.³

What’s the Latest Research?

In addition to lifestyle interventions, the only medically approved treatment options for PCOS are metformin and oral contraceptives.  The use of GLP-1s with or without metformin is being studies for women with PCOS.  In one meta-analysis, the benefits of GLP-1s versus metformin were compared in women with PCOS.  GLP-1s showed to be better at improving insulin sensitivity and reducing body mass index than metformin alone.  They had similar effects on menstrual regularity, testosterone and androgen levels, hirsutism, fasting blood glucose, fasting insulin, and total cholesterol when compared.⁴

GLP-1s are also shown to have a positive effect in pregnancy rates in women with PCOS.  A randomized clinical trial looked at pregnancy rates in women on the GLP-1 exenatide 10 mg twice daily or metformin 1000 mg twice daily for 12 weeks.  In the second 12 weeks, all participants received metformin alone.  The rate of pregnancy in the participants treated with exenatide was significantly higher than those treated with metformin alone.⁵

While more research needs to be done on the specific impacts of GLP-1s on PCOS, current studies show that there may be a significant benefit.  There is evidence that GLP-1s affect the mechanisms involved in insulin resistance, decrease inflammation, and reduce oxidative stress.  They also show improvements in fertility.⁶

Risks and Considerations

GLP-1s are not without side effects and risks for women with PCOS.  Common side effects include nausea, vomiting, headaches, gas, and diarrhea.  Not consuming enough protein is also a concern because as appetite decreases, overall food intake does as well.  A lack of protein can lead to decreased muscle mass and slowed metabolism.  Further, GLP-1s can affect the absorption of vitamin B12 as well as other vitamins.  Be sure to consult a registered dietitian if you are considering starting these medications to ensure you are receiving the proper nutrition.

Current data suggests that these medications need to be taken forever and when individuals go off of them, they gain the weight they lost back.  Many people find it difficult to tolerate the side effects.  Additionally, those who become pregnant need to stop taking GLP-1s as safety data during pregnancy are lacking.  Making lifestyle changes along with taking GLP-1s is essential in the event that an individual needs to stop taking them or doesn’t want to be dependent on them forever.

Finally, if you struggle with an eating disorder or disordered eating, it is advised not to start GLP-1s.  There is also a high prevalence of eating disorders in the PCOS population.⁷  Decreased hunger cues and weight loss can be triggering for someone in recovery or working on recovering from an eating disorder.  Speak with your treatment team before starting one of these medications.

Bottom Line

Research shows numerous benefits of taking GLP-1s for PCOS for their effect on insulin resistance, stabilizing fasting blood sugar levels and androgen levels, and fertility.  Be sure to speak with your doctor and registered dietitian to decide if these medications are useful addition to your PCOS treatment.

1. Jiang Y, Wang Z, Ma B, et al. GLP-1 Improves Adipocyte Insulin Sensitivity Following Induction of Endoplasmic Reticulum Stress. Front Pharmacol. 2018;9:1168. Published 2018 Oct 16. doi:10.3389/fphar.2018.01168
2. Siddiqui S, Mateen S, Ahmad R, Moin S. A brief insight into the etiology, genetics, and immunology of polycystic ovarian syndrome (PCOS). J Assist Reprod Genet. 2022;39(11):2439-2473. doi:10.1007/s10815-022-02625-7
3. Jensterle M, Herman R, Janež A. Therapeutic Potential of Glucagon-like Peptide-1 Agonists in Polycystic Ovary Syndrome: From Current Clinical Evidence to Future Perspectives. Biomedicines. 2022;10(8):1989. Published 2022 Aug 16. doi:10.3390/biomedicines10081989
4. Han Y, Li Y, He B. GLP-1 receptor agonists versus metformin in PCOS: a systematic review and meta-analysis. Reprod Biomed Online. 2019;39(2):332-342. doi:10.1016/j.rbmo.2019.04.017
5. Liu X, Zhang Y, Zheng SY, et al. Efficacy of exenatide on weight loss, metabolic parameters and pregnancy in overweight/obese polycystic ovary syndrome. Clin Endocrinol (Oxf). 2017;87(6):767-774. doi:10.1111/cen.13454
6. Bednarz K, Kowalczyk K, Cwynar M, et al. The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome. Int J Mol Sci. 2022;23(8):4334. Published 2022 Apr 14. doi:10.3390/ijms23084334
7. Krug I, Giles S, Paganini C. Binge eating in patients with polycystic ovary syndrome: prevalence, causes, and management strategies. Neuropsychiatr Dis Treat. 2019;15:1273-1285. Published 2019 May 16. doi:10.2147/NDT.S168944