Combined liraglutide and metformin therapy in overweight or obese women with polycystic ovary syndrome: A systematic review and meta-analysis

Abstract

Purpose: Overweight or obese women with polycystic ovary syndrome (PCOS) often experience significant metabolic and hormonal disturbances. This systematic review and meta-analysis evaluated whether liraglutide combined with metformin is more effective than metformin alone in improving glycaemic control, lipid metabolism, body mass index (BMI) and sex hormone profiles in this population. Methods: We systematically searched PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, Weipu, SinoMed and Wanfang Data for randomised controlled trials (RCTs) comparing liraglutide plus metformin to metformin monotherapy in overweight or obese women with PCOS. Primary outcomes included fasting plasma glucose (FPG), 2-h postprandial glucose, HbA1c, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), BMI, sex hormones (luteinising hormone [LH], follicle-stimulating hormone [FSH], total testosterone [TT]) and lipid profiles (total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C] and high-density lipoprotein cholesterol [HDL-C]). Subgroup analyses were conducted by treatment duration, lifestyle intervention and baseline BMI. Results: A total of 19 RCTs involving 1657 women with PCOS were included. Compared to metformin alone, the combination of liraglutide and metformin significantly improved glycaemic metabolism: FPG (standard mean difference = −1.92, 95% confidence interval [CI] [−2.43, −1.41]; I2 = 95%), 2-h postprandial glucose (−2.87, [−3.70, −2.05]; 97%), HbA1c (−2.91, [−3.84, −1.98]; 96%), HOMA-IR (−2.29, [−2.98, −1.60]; 97%) and fasting insulin (−0.75, [−1.41, −0.09]; 94%). BMI was also significantly reduced (−1.64, [−2.38, −0.89]; 97%). Hormonal indicators improved, including LH (−1.48, [−1.83, −1.14]; 85%), FSH (−1.17, [−1.62, −0.73]; 92%) and TT (−0.66, [−1.30, −0.03]; 95%). In terms of lipid metabolism, reductions were observed in TC (−2.34, [−3.67, −1.01]; 98%), TG (−0.58, [−0.96, −0.21]; 79%) and LDL-C (−0.79, [−1.36, −0.22]; 91%), while HDL-C increased (0.67, [0.21, 1.13]; 83%). Longer treatment duration (≥16 weeks) and lack of lifestyle intervention were associated with greater improvements in insulin resistance and hormone levels. Lipid outcomes were consistent across subgroups, while glycaemic improvements were more notable in overweight versus obese women. Sensitivity analyses supported the robustness of findings. However, the overall certainty of evidence was low due to risk of bias and heterogeneity. Conclusion: The combination of liraglutide and metformin resulted in greater improvements in body weight, blood sugar levels, insulin sensitivity, hormone balance (including LH, FSH and testosterone) and cholesterol profiles. These findings indicate that the combined therapy offers more comprehensive metabolic and hormonal benefits than metformin alone for women with PCOS.