SGLT2 Inhibitors for PCOS: Best Metabolic Results When Combined with GLP-1 Drugs | Research

The takeaway

A systematic review of 5 trials found SGLT2 inhibitors improved metabolic and hormonal parameters in PCOS, with the combination of SGLT2i plus a GLP-1 receptor agonist producing the most pronounced improvements in body composition and metabolism.

SGLT2i + GLP-1 RA = best combo
Combining an SGLT2 inhibitor with a GLP-1 receptor agonist produced the most pronounced improvements in body composition and metabolic parameters in PCOS patients

What the researchers found

Across five RCTs studying canagliflozin, empagliflozin, dapagliflozin, and licogliflozin in 269 overweight/obese PCOS patients, SGLT2 inhibitors reduced insulin resistance (lower HOMA-IR, insulin, and fasting glucose), decreased body weight, BMI, waist circumference, and total body fat, and lowered triglycerides. DHEAS levels decreased in two trials, though total testosterone and free androgen index generally did not change.

Notably, the combination of SGLT2i with a GLP-1 receptor agonist produced the most prominent improvements in body composition and metabolic parameters, while SGLT2i combined with metformin showed better effects on hormonal parameters. Menstrual irregularity and hirsutism scores improved. LDL cholesterol slightly increased in most trials. Adverse effects were mostly mild genital infections.

Why it matters

PCOS is the most common hormonal disorder in women of reproductive age, affecting 6-12% worldwide. Current treatments are limited and often address only individual symptoms. SGLT2 inhibitors target the underlying insulin resistance that drives much of PCOS pathology. The finding that combining SGLT2i with GLP-1 drugs produces superior metabolic improvements could establish a new combination therapy paradigm for PCOS that addresses the metabolic root cause rather than just managing symptoms.

How the study worked

Systematic review of randomized controlled trials identified through electronic database searches. Inclusion criteria: RCTs of overweight/obese PCOS patients receiving SGLT2 inhibitors versus placebo or non-hormonal active comparators. Five trials with 269 participants were included. Outcomes assessed included metabolic parameters (insulin resistance, glucose, lipids), hormonal markers (testosterone, DHEAS), anthropometric measures (weight, BMI, waist), body composition, and clinical features (menstrual regularity, hirsutism).

What this study cannot tell us

Only 5 RCTs with 269 total participants were available, providing limited statistical power. The studies used different SGLT2 inhibitors at different doses, limiting comparability. Follow-up durations were relatively short. No meta-analysis was performed (systematic review only). The GLP-1 RA combination data came from limited studies. Long-term effects on fertility, pregnancy outcomes, and cardiovascular risk were not assessed. SGLT2 inhibitors are not approved for PCOS, so all use is off-label.

How to read the evidence

This is a systematic review of 5 randomized controlled trials — a moderately strong evidence synthesis. However, the small total sample (269 patients), heterogeneous study designs, and lack of meta-analysis limit the conclusions. The evidence is promising but preliminary.

When this study was published

Published in 2025, this is a current review capturing the emerging evidence on SGLT2 inhibitors for PCOS. The field is evolving rapidly as more trials of these drug classes in PCOS populations are completed.

The bigger picture

PCOS management has been dominated by oral contraceptives and metformin for decades. The emergence of newer drug classes — SGLT2 inhibitors and GLP-1 receptor agonists — offers mechanistically distinct approaches that target insulin resistance and metabolic dysfunction more directly. This review positions the SGLT2i + GLP-1 RA combination as a potentially powerful dual-mechanism therapy for PCOS, echoing the success of this combination in type 2 diabetes. As more women with PCOS are prescribed these drugs off-label, this evidence helps guide rational combination strategies.

Questions still open

Could the SGLT2i + GLP-1 RA combination become a first-line metabolic therapy for PCOS, potentially replacing metformin?
Would newer GLP-1 drugs like semaglutide or tirzepatide combined with SGLT2i produce even stronger results in PCOS?
Do the metabolic improvements from SGLT2i translate to improved fertility outcomes in women with PCOS?

Common questions

What does insulin resistance have to do with PCOS?

Insulin resistance is a core feature of PCOS in many women — their bodies produce excess insulin to compensate for cells that don't respond normally. This excess insulin stimulates the ovaries to produce more male hormones (androgens), which cause symptoms like acne, excess hair growth, and irregular periods. By targeting insulin resistance, SGLT2 inhibitors and GLP-1 drugs address one of the root causes of PCOS rather than just masking symptoms.

Why would combining SGLT2 inhibitors with GLP-1 drugs work better than either alone?

SGLT2 inhibitors work in the kidneys by causing excess sugar to be excreted in urine, while GLP-1 drugs work in the brain and pancreas to reduce appetite and improve insulin secretion. Together, they attack insulin resistance and metabolic dysfunction from two different directions, which is why the combination produced the best metabolic and body composition improvements in this review of PCOS patients.

Read the original research

Role of Sodium-Glucose Cotransporter-2 Inhibitors in Managing Polycystic Ovary Syndrome: A Systematic Review.

TouchREVIEWS in endocrinology, 21(1), 32-41

View on PubMed ↗Publisher’s paper ↗

Citation

Kamrul-Hasan, Abm; Mondal, Sunetra; Zahura Aalpona, Fatema Tuz; Nagendra, Lakshmi; Dutta, Deep. (2025). Role of Sodium-Glucose Cotransporter-2 Inhibitors in Managing Polycystic Ovary Syndrome: A Systematic Review.. TouchREVIEWS in endocrinology, 21(1), 32-41. https://doi.org/10.17925/EE.2025.21.1.2