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GLP-1 Agonists & PCOS Research Overview

Polycystic ovary syndrome affects somewhere between 6% and 20% of women of reproductive age, depending on which diagnostic criteria you use.

Polycystic ovary syndrome affects somewhere between 6% and 20% of women of reproductive age, depending on which diagnostic criteria you use. It is the most common endocrine disorder in this population, and for millions of women, it means some combination of irregular periods, excess androgen production, insulin resistance, weight gain, acne, and difficulty getting pregnant.

For decades, the treatment options have been limited. Metformin. Oral contraceptives. Lifestyle modification. Spironolactone for androgen symptoms. Clomiphene for fertility. None of these address the full metabolic picture of PCOS, and many women find metformin alone produces only modest weight loss.

Then GLP-1 receptor agonists arrived — first for type 2 diabetes, then for obesity. And researchers started asking an obvious question: if these drugs improve insulin resistance, drive substantial weight loss, and alter metabolic signaling, what can they do for PCOS?

The short answer: quite a lot, according to a growing body of clinical evidence. Here is what we know so far.

Table of Contents

The PCOS-Insulin Connection: Why GLP-1 Drugs Make Biological Sense

PCOS is not just a reproductive disorder. It is a metabolic one. Roughly 70% of women with PCOS are insulin resistant, and approximately 80% are overweight or obese. These metabolic features are not coincidental — they are mechanistically linked to the hormonal dysfunction that defines the condition.

Here is how the cycle works: hyperinsulinemia (chronically elevated insulin) acts as a co-gonadotropin on the ovary, directly stimulating theca cells to produce excess androgens like testosterone. Insulin also suppresses hepatic production of sex hormone-binding globulin (SHBG), the protein that mops up free testosterone in the bloodstream. Less SHBG means more bioavailable testosterone. On top of that, insulin amplifies the adrenal glands' sensitivity to ACTH stimulation, driving adrenal androgen production as well.

The result is a self-reinforcing loop. Excess androgens promote visceral fat deposition, which worsens insulin resistance, which raises insulin levels further, which drives more androgen production. Breaking this cycle at the metabolic level — through weight loss and improved insulin sensitivity — is one of the most effective ways to improve every downstream PCOS symptom.

This is exactly what GLP-1 receptor agonists do. By enhancing glucose-dependent insulin release, suppressing glucagon, slowing gastric emptying, and acting on central appetite circuits, these drugs produce substantial weight loss and significant improvements in insulin sensitivity. For women with PCOS, that means hitting the condition at its metabolic root.

How GLP-1 Receptor Agonists Work in PCOS

GLP-1 receptor agonists (GLP-1RAs) mimic the incretin hormone GLP-1, which is released by the gut after eating. They bind to GLP-1 receptors throughout the body — not just in the pancreas, but in the brain, gut, liver, adipose tissue, and, notably, the reproductive system.

In women with PCOS, GLP-1RAs produce effects across several domains:

EffectMechanism
Weight lossCentral appetite suppression, delayed gastric emptying, reduced caloric intake
Improved insulin sensitivityReduced fasting insulin, lower HOMA-IR, better glucose disposal
Reduced androgensLower free testosterone, lower androstenedione, increased SHBG
Anti-inflammatoryReduced TNF-alpha, IL-6, and CRP in ovarian and systemic tissues
Improved lipid profilesLower triglycerides, improved total cholesterol ratios
Menstrual regulationRestored ovulatory cycles in a majority of treated patients

Importantly, GLP-1 receptors have been identified throughout the female reproductive tract, suggesting that some of these benefits may extend beyond indirect metabolic improvement. Reduced levels of endogenous GLP-1 have been documented in women with PCOS compared to controls, which some researchers interpret as evidence that GLP-1 deficiency itself may contribute to the condition's pathophysiology.

Liraglutide: The Most-Studied GLP-1 Agonist in PCOS

Liraglutide (Victoza/Saxenda) has the deepest evidence base in PCOS, thanks largely to the work of Mojca Jensterle and colleagues at the University Medical Centre Ljubljana, who have run multiple randomized trials since 2014.

Key Trials

Jensterle et al., 2015 — Liraglutide vs. Metformin (Pilot RCT) In a 12-week study of 45 obese women with PCOS, liraglutide 1.2 mg daily produced an average weight loss of 3.1 kg, compared to just 0.2 kg with metformin 1000 mg twice daily. Liraglutide was statistically superior for weight (p = 0.022), BMI (p = 0.020), and waist circumference (p = 0.007). Source: Journal of Ovarian Research, 2015

Jensterle et al., 2017 — Low-Dose Combination vs. High-Dose Monotherapy Thirty obese women with PCOS (mean BMI 38.3) were randomized to either low-dose liraglutide (1.2 mg) plus metformin or high-dose liraglutide (3 mg) alone for 12 weeks. The high-dose liraglutide group lost 6.3 kg versus 3.6 kg in the combination group. BMI and waist circumference reductions were significantly greater with liraglutide 3 mg monotherapy. Source: BMC Endocrine Disorders, 2017

Liraglutide and IVF Outcomes A randomized open-label trial found that 3 months of preconception liraglutide plus metformin in obese women with PCOS produced a markedly higher IVF pregnancy rate than metformin alone — 85.7% versus 28.6% (p = 0.03). Both groups lost similar amounts of weight, suggesting liraglutide may have direct reproductive benefits beyond its metabolic effects. Source: Reproductive BioMedicine Online, 2017

Liraglutide and Eating Behavior In 36 obese women with PCOS who switched from metformin to liraglutide 1.2 mg for 12 weeks, average weight loss was 3.8 kg, with significant improvements in emotional eating and uncontrolled eating scores on the Three-Factor Eating Questionnaire. Source: PubMed, 2014

Exenatide Trials: Twice-Daily Injections With Big Results

Exenatide (Byetta), a shorter-acting GLP-1 agonist, has been studied in several PCOS trials, particularly in Chinese populations.

Liu et al., 2017 — The Largest Exenatide PCOS Trial (n=176)

This 24-week open-label trial randomized 176 overweight/obese women with PCOS to either exenatide 10 mcg twice daily or metformin 1000 mg twice daily for the first 12 weeks, followed by metformin alone for the second 12 weeks.

After the initial 12-week phase, the exenatide group showed:

  • Greater weight loss: 4.29 kg vs. 2.28 kg (p < 0.001)
  • Greater fat reduction: 4.67% vs. 1.11% total body fat (p < 0.001)
  • Better insulin resistance improvement: HOMA-IR decreased by 1.30 vs. 0.59 (p < 0.001)
  • Higher menstrual frequency ratio: 0.62 vs. 0.37 (p < 0.001)

Short-term pregnancy rates were also significantly higher in the exenatide group — 43.6% versus 18.7% at 24 weeks. However, long-term follow-up at 64 weeks found no significant difference in total pregnancy rate or outcomes between groups. Source: Clinical Endocrinology, 2017

Elkind-Hirsch et al. — Combination Therapy

A 24-week trial showed that exenatide plus metformin produced 6.0 kg of weight loss, compared to 3.2 kg with exenatide alone and 1.6 kg with metformin alone. The combination also produced the greatest improvements in menstrual cycle frequency, hormonal profiles, and adiponectin levels. Source: PubMed, 2008

Prediabetes Remission

In a trial of 150 women with PCOS and impaired glucose tolerance, the prediabetes remission rate was 64% with exenatide plus metformin, 56% with exenatide alone, and 32% with metformin alone — a significant finding given the high diabetes conversion rates in PCOS populations.

Semaglutide: The Newest and Most Potent Data

Semaglutide — the active ingredient in Ozempic and Wegovy — is the most potent GLP-1 agonist currently available for weight loss, and it is now generating PCOS-specific data.

Low-Dose Semaglutide (0.5 mg) — Pilot Study

Twenty-seven obese women with PCOS who had not responded to lifestyle modification received semaglutide 0.5 mg subcutaneously once weekly. After three months, average weight loss was 7.6 kg with a mean BMI reduction of 3.1 points. Nearly 80% of patients achieved at least 5% body weight reduction. By six months, mean weight loss reached 11.5 kg, and BMI dropped from 34.4 to 29.4. Eighty percent of responders normalized their menstrual cycles, and insulin and HOMA-IR both improved independently of weight loss. Source: PMC, 2023

Semaglutide and Androgens

Jensterle et al. (2023) reported that 12 weeks of semaglutide treatment produced statistically significant reductions in androstenedione and free testosterone, alongside increased SHBG — a pattern consistent with reduced hyperandrogenism. Tongue fat volume also decreased, a novel finding suggesting semaglutide's effects on body composition may be more widespread than previously recognized. Source: Diabetes, Obesity and Metabolism, 2023

Semaglutide + Metformin Combination (2025 RCT)

A 2025 prospective randomized controlled trial compared semaglutide 1 mg weekly plus metformin 1000 mg twice daily versus metformin alone in 100 overweight/obese women with PCOS over 16 weeks. The combination group showed significantly greater reductions in body weight, testosterone, and free androgen index, with a greater increase in SHBG. Only the combination group achieved significant reductions in DHEA-S. Menstrual irregularities improved in both groups, but natural pregnancy rates were higher with combination therapy. Source: PMC, 2025

Long-Term Data After Semaglutide Withdrawal

A 2-year observational study tracked obese women with PCOS who received semaglutide followed by discontinuation while continuing metformin. Free testosterone decreased significantly during treatment (from 6.16 to 4.12 nmol/L, p = 0.012) and — importantly — did not bounce back after semaglutide was stopped. Women regained about one-third of their weight loss, but still maintained statistically significant net weight loss from baseline at 2 years. Source: Frontiers in Endocrinology, 2024

2025 Meta-Analysis

A meta-analysis published in Gynecological Endocrinology (2025) evaluated semaglutide's impact across multiple PCOS trials and found that doses of 1.0 mg/week or higher and patients with baseline BMI above 28 showed the greatest benefits. Semaglutide significantly improved BMI and lipid profiles across all analyzed studies. Source: Gynecological Endocrinology, 2025

Tirzepatide: The Dual Agonist With Real-World PCOS Data

Tirzepatide (Mounjaro/Zepbound) is a dual GIP/GLP-1 receptor agonist that produces even more weight loss than semaglutide in general obesity populations. Its PCOS data are newer but already striking.

Real-World Study of 4,241 Women (ObesityWeek 2025)

The largest tirzepatide-PCOS study to date — a retrospective analysis of 4,241 women with PCOS enrolled in a U.K. digital weight-loss program — was presented at ObesityWeek 2025. Median age was 34 years and median BMI was 35.56.

The results were remarkable:

TimepointMean Weight Loss% Achieving ≥5% Loss% Achieving ≥10% Loss% Achieving ≥15% Loss
10 months18.81%96.6%90.1%75.96%

Women who engaged with digital coaching and weekly weight tracking lost even more — 21.02% versus 17.23% for those not digitally engaged. Source: Medscape, 2025

Bangladesh Retrospective Study (2025)

A multicenter study of 56 women with PCOS-associated obesity treated with tirzepatide found a 9.54% mean weight reduction, with BMI dropping from 36.51 to 32.49 (p = 0.0002). Irregular menstrual cycles decreased from 85.7% to 32.1% of participants, ovarian cyst prevalence dropped from 89.3% to 41%, and insulin resistance improved in 30% of patients (from 80.4% to 50%). Source: International Journal of Diabetes and Endocrinology, 2025

Among women with PCOS, semaglutide or tirzepatide prescribing jumped from 2.4% in 2021 to 17.6% in 2025 — a more than seven-fold increase — though nearly all prescriptions were tied to co-occurring obesity or type 2 diabetes diagnoses. Source: Truveta Research, 2025

Head-to-Head: GLP-1 Agonists vs. Metformin for PCOS

Multiple meta-analyses have compared GLP-1RAs directly to metformin in PCOS populations. The aggregate findings show clear separation in some areas and overlap in others.

OutcomeGLP-1RAs vs. Metformin
BMI reductionGLP-1RAs significantly better (SMD -1.02, p = 0.02)
Insulin sensitivityGLP-1RAs significantly better (SMD -0.40, p = 0.02)
Waist circumferenceGLP-1RAs produce greater reductions (MD -5.16 cm in meta-analysis)
Weight loss (>5%)GLP-1 monotherapy more likely to achieve this threshold
Testosterone reductionNo significant difference in most head-to-head studies
Menstrual regularityNo significant difference
NauseaSignificantly higher with GLP-1RAs (p = 0.02)
HeadacheSignificantly higher with GLP-1RAs

The bottom line of these comparisons: GLP-1RAs outperform metformin for weight loss and insulin sensitivity, but the two classes appear roughly equivalent for reproductive hormone outcomes and menstrual regulation when used as monotherapy. Combination therapy — GLP-1RA plus metformin — appears to outperform either drug alone across most outcomes.

Source: Reproductive BioMedicine Online meta-analysis; Source: Scientific Reports, 2025

GLP-1 Agonists, Fertility, and Pregnancy

For women with PCOS who want to conceive, the fertility data on GLP-1RAs are among the most interesting — and the most complicated — findings in this research area.

What the Data Show

A systematic review and meta-analysis of 11 RCTs (840 patients) found that GLP-1RA use was associated with a 72% higher natural pregnancy rate compared to controls (RR: 1.72, 95% CI 1.22–2.43, p = 0.002). The improvement in fertility appears to stem from restored ovulation, reduced insulin resistance, weight loss, and — possibly — direct effects on reproductive tissue. Source: BMC Endocrine Disorders, 2023

The IVF data are particularly notable. As described above, liraglutide plus metformin produced an 85.7% IVF pregnancy rate versus 28.6% with metformin alone — despite equivalent weight loss in both groups. This result has been interpreted as evidence that GLP-1RAs may act directly on the reproductive system, beyond their metabolic effects.

The Critical Caveat

GLP-1 receptor agonists are not approved for use during pregnancy. Animal data have shown reproductive toxicity, and human safety data are limited. Across available human pregnancy exposure data for liraglutide, 47.7% resulted in live births, 34.2% in fetal loss (mostly spontaneous abortions), and 10% were terminated.

Clinical guidelines recommend discontinuing GLP-1RAs at least one to two months before conception — and some reproductive endocrinologists recommend a three-month washout before starting fertility treatments like ovulation induction, IUI, or IVF.

There is also a practical concern: tirzepatide can delay gastric emptying, which may reduce absorption of oral contraceptives. Women starting or adjusting tirzepatide doses should use a backup barrier method. Source: PMC, 2025

For women with PCOS navigating these decisions, the emerging strategy is preconception GLP-1RA treatment to optimize metabolic and hormonal parameters, followed by discontinuation and a washout period before attempting pregnancy. This approach shows promise in the data but requires careful coordination with a reproductive endocrinologist.

Preclinical Research: How GLP-1 Drugs Act on the Ovaries

Some of the most mechanistically interesting PCOS research involves animal models.

A 2024 study in mice found that semaglutide reduces ovarian inflammation through the AMPK/SIRT1/NF-kB signaling pathway. Female C57BL/6J mice given DHEA to induce PCOS showed elevated ovarian levels of inflammatory cytokines TNF-alpha, IL-6, and IL-1beta — all of which contribute to insulin resistance in granulosa cells by disrupting GLUT4 translocation and insulin receptor signaling. Semaglutide treatment activated AMPK, upregulated the anti-inflammatory deacetylase SIRT1, and suppressed NF-kB, reducing ovarian inflammation in a dose-dependent manner. Source: PMC, 2024

Another 2025 preclinical study showed that semaglutide alleviates ovarian oxidative stress and autophagy via the PI3K/AKT/mTOR pathway in PCOS mice — suggesting yet another mechanism by which these drugs may improve ovarian function.

Separate research on GLP-1/estrogen conjugate molecules has demonstrated superior efficacy over standard GLP-1 agonists and metformin for metabolic PCOS traits, including restoration of normal estrous cycling in mice. These dual-agonist approaches represent a potential next generation of PCOS-targeted therapies. Source: Nature Communications, 2024

Safety, Side Effects, and Practical Considerations

Side Effects in PCOS Populations

The side effect profile of GLP-1RAs in PCOS mirrors what is seen in general obesity and diabetes populations. The most common adverse events:

  • Nausea: 20–40% of patients, usually worst during dose titration
  • Vomiting: Reported in some trials, typically self-resolving
  • Dizziness and headache: More common with GLP-1RAs than metformin
  • Heartburn: Reported in 42.9% of tirzepatide-treated women in one PCOS study
  • General weakness: Noted during initial treatment weeks

Most side effects are mild and resolve within the first few weeks. Slow dose titration helps. Discontinuation rates in PCOS trials have been low.

Contraindications

Before starting a GLP-1RA, patients should be screened for personal or family history of medullary thyroid carcinoma or MEN2 syndrome, history of pancreatitis, and severe gastrointestinal disease.

Regulatory Status

No GLP-1 receptor agonist is FDA-approved specifically for PCOS. Prescriptions for women with PCOS currently require an obesity (BMI ≥ 30) or type 2 diabetes diagnosis. The American Society for Reproductive Medicine has included GLP-1RAs as options for managing obesity in women with PCOS, which represents a significant step toward broader clinical acceptance.

Who Benefits Most

The data suggest GLP-1RAs are most effective for PCOS patients who are overweight or obese with metabolic dysfunction — particularly those with insulin resistance, elevated BMI, and poor response to metformin alone. There is limited evidence supporting their use in normal-weight women with PCOS.

For women weighing their options for hormonal balance and metabolic health, understanding where GLP-1 agonists fit alongside other interventions is important. Women over 40 with PCOS may find these drugs particularly relevant as metabolic risk increases with age.

The Bottom Line

The clinical evidence for GLP-1 receptor agonists in PCOS has grown rapidly, particularly between 2023 and 2025. Across more than a dozen randomized controlled trials and multiple meta-analyses, these drugs consistently outperform metformin for weight loss and insulin sensitivity improvement in obese women with PCOS. The combination of a GLP-1RA with metformin appears to be the most effective approach tested so far — producing the greatest improvements in weight, androgens, menstrual regularity, and pregnancy rates.

Semaglutide and tirzepatide, the two most potent agents in the class, are generating the most impressive data. Semaglutide shows 7–11 kg of weight loss at low doses over 3–6 months, with demonstrated androgen reduction and menstrual cycle normalization. Tirzepatide, in the largest real-world PCOS cohort studied to date, produced nearly 19% body weight loss at 10 months — with over 96% of women losing at least 5%.

There are 13 registered clinical trials currently investigating GLP-1RAs for PCOS, enrolling approximately 1,066 participants. The next 2–3 years should bring more definitive answers on long-term reproductive outcomes, optimal dosing, and which PCOS phenotypes respond best.

What the evidence will not resolve, at least not soon, is the fundamental tension: these drugs must be stopped before pregnancy, and stopping them often means regaining weight. How to time preconception treatment, manage weight regain during washout, and preserve metabolic gains through pregnancy are questions that will define the next phase of this research.

For now, GLP-1 receptor agonists represent the most significant new pharmacological tool for PCOS management in at least a decade. They are not a cure. They do not address every PCOS phenotype. But for the majority of women with PCOS who are overweight and insulin resistant, the data are difficult to ignore.

References

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