Comparison of GLP-1 Receptor Agonists Combined with Metformin Versus Metformin Alone in the Management of PCOS: A Comprehensive Meta-Analysis

Jan 29, 2025Reproductive sciences (Thousand Oaks, Calif.)

Comparing GLP-1 Drugs Plus Metformin to Metformin Alone for Managing Polycystic Ovary Syndrome

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Abstract

The combination of GLP1 receptor agonists and metformin resulted in a 1.37 kg mean reduction in body weight compared to metformin alone.

Significant reductions in body mass index (BMI) were observed, with a mean difference of -0.88 kg/m².
Waist circumference decreased by a mean of -2.46 cm in the combination therapy group.
Fasting glucose levels showed a mean reduction of -0.30, indicating improved glucose control.
Insulin sensitivity improved in the combination group, with a mean change in HOMA-IR of -1.58.
Sex hormone-binding globulin (SHBG) levels increased by a mean of 10.04 in the GLP1RA plus metformin group.
No significant differences in adverse events were found between the two treatment groups.

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This study compared the efficacy and safety of glucogan-like peptide-1 receptor agonists (GLP1RAs) combined with metformin versus metformin alone in women with polycystic ovary syndrome (PCOS). A systematic search of "PubMed", "EMBASE", "Cochrane Library", and "Web of Science", "Google Scholar" was conducted up to September 2024. Studies were included if they were RCTs investigating the combination of GLP1RAs and metformin in women diagnosed with PCOS. Eligible studies compared this combination therapy to metformin alone. Primary outcomes included changes in body weight, BMI, waist circumference, fasting glucose, HOMA-IR, androgen levels, and sex hormone-binding globulin (SHBG). Meta-analysis was performed using RevMan 5.4 software. Eight RCTs with a total of 337 participants were included. The combination of GLP1RAs and metformin resulted in significant reductions in body weight (mean difference [MD]=-1.37 kg, 95% CI [-2.07, -0.67]; P = 0.0001), BMI (MD= -0.88 kg/m², 95% CI [-1.37, -0.39]; P = 0.0005), waist circumference (MD= -2.46 cm, 95% CI [-3.59,-1.33]; P < 0.0001), fasting glucose level (MD= -0.30, 95% CI [-0.42,-0.17]; P < 0.0001), and glucose level at 2 h after OGTT (MD= -1.58, 95% CI [-2.10,-1.06]; P < 0.0001) compared to metformin alone. Improvements in insulin sensitivity (HOMA-IR) in GLP1RA + Met group were also observed (MD=-1.58, 95% CI [-2.10, -1.06]; P < 0.0001) comparing to Met group. Hormonal outcomes demonstrated an increase in SHBG (MD = 10.04, 95% CI [7.06, 13.01]; P < 0.0001). Adverse events were not different between GLP1RA + Met and Met groups. Collectivley, combination of GLP1RAs and metformin provides superior benefits over metformin alone in reducing body weight, improving insulin sensitivity, and regulating hormonal imbalances in women with PCOS.

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Comparison of GLP-1 Receptor Agonists Combined with Metformin Versus Metformin Alone in the Management of PCOS: A Comprehensive Meta-Analysis

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