Comparative analysis of glucagon-like peptide-1 receptor agonists, metformin, and inositol in improving anthropometric and metabolic outcomes in women with polycystic ovary syndrome: a network meta-analysis
In brief
GLP-1 plus metformin drops weight by about 5.5 kg in women with PCOS
A network meta-analysis of 16 trials found that adding a GLP-1 receptor agonist to metformin reduced body weight by roughly 5.5 kg and BMI by about 2 points, outperforming metformin or myoinositol alone; waist circumference also fell by nearly 5 cm with GLP-1 alone. No significant change in insulin resistance was seen, and the evidence was heterogeneous, highlighting the need for longer-term head-to-head studies.
- Journal
- Frontiers in endocrinology (Q1)
- Published
- 3 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Asad Omarion, Yaman Ayasa, Zainab Omarion, Batoul Jayouse, Hazem Ayesh
- PMID
- 42490840
- DOI
- 10.3389/fendo.2026.1833904
Why clinicians should know about it
- Picked for Physiology (medical) (top studies of the week, 26 July 2026).
- Picked for Pharmacology (medical) (paper of the day, 24 July 2026).
Abstract
BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder characterized by obesity, insulin resistance, and cardiometabolic risks. Lifestyle intervention is first-line therapy, but drug therapy is often necessary. Common treatments include metformin, myoinositol, and glucagon-like peptide-1 (GLP-1) receptor agonists. The comparative metabolic efficacy of these treatments remains unclear. METHODS: We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) according to PRISMA-NMA guidelines. Eligible studies recruited non-menopausal women with PCOS and evaluated GLP-1 receptor agonists, metformin, or myoinositol (± folic acid [FA]) alone or in combination versus placebo or active comparators. The primary outcome was body weight change, while secondary outcomes included body mass index (BMI), waist circumference, and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Outcomes were synthesized using a frequentist random-effects NMA, and the CINeMA framework was used to assess certainty. RESULTS: Sixteen RCTs were included. GLP-1 + metformin was the most effective intervention for weight reduction (MD -5.58 kg; 95% CI -8.57 to -2.59) and BMI decrease (MD -2.17; 95% CI -2.77 to -1.58). GLP-1 monotherapy also showed decreases in weight (MD -5.22 kg) and BMI (MD -2.00). Waist circumference was significantly reduced by GLP-1 alone (MD -4.70 cm). None ofthe interventions showed significant effects on HOMA-IR, and results were marked by heterogeneity. Sensitivity analyses confirmed robustness for weight and BMI outcomes. CONCLUSIONS: GLP-1 receptor agonists combined with metformin appear to be the most effective pharmacologic therapies for anthropometric improvement, specifically body weight and BMI reduction, in women with PCOS. These conclusions are limited to anthropometric and metabolic parameters, reproductive, endocrine, and patient-centered outcomes were not evaluated in this analysis and therefore no claims of overall superiority in PCOS management can be made. Further long-term and head-to-head RCTs including a broader range of outcomes are needed. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/zyhws/, identifier 10.17605/OSF.IO/ZYHWS.
Abstract as published, via PubMed.
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