Comparative Efficacy and Safety of Liraglutide Versus Metformin in Women With Polyendocrine Metabolic Ovarian Syndrome (PMOS): A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Polyendocrine metabolic ovarian syndrome (PMOS), previously known by the name ‘polycystic ovary syndrome (PCOS),' is a common and complex endocrine-metabolic disorder affecting approximately one in eight women. PMOS is increasingly regarded as a multisystem disorder rather than only a gynaecological condition. Exclusive of weight loss, metformin has been the mainstay pharmacological therapy in the treatment of PMOS; a new contender for the management of this condition is liraglutide. Liraglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RAs) and has gained increasing interest because it targets appetite regulation, body weight, and glycemic control as well as insulin sensitivity. There remains no comprehensive and up-to-date synthesis specifically comparing liraglutide versus metformin across clinically important outcomes in women with PMOS. This systematic review and meta-analysis aims to comprehensively evaluate these outcomes and provide evidence to guide individualized therapeutic decision-making. This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines (PRISMA). The research protocol was registered under the International Prospective Register of Systematic Reviews (PROSPERO), and the proposal is available under registration number CRD420261435182. No statistically significant difference in BMI between liraglutide and metformin (mean difference (MD)=0.25, 95% confidence interval (CI): -7.30-7.79, P=0.95, I²=82%, p=0.02). The pooled result of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) favored metformin but showed no statistical difference between liraglutide and metformin (MD=0.94, 95% CI: -0.09-1.97, P=0.07, I²=0%, chi-square=0.14, p=0.71). Although the pooled effect favored metformin due to a higher frequency of the menstrual cycle, there was no significant difference between liraglutide and metformin (MD = -1.42, 95% CI: -4.57-1.73, P = 0.38, I² = 75%). A fixed-effect meta-analysis demonstrated no significant difference in fasting glucose levels between liraglutide and metformin (MD=-0.01 mmol/l, 95 % CI: - 0.82-0.80, P=0.98, I2=37%, p=0.21). No significant difference in fasting insulin levels between liraglutide and metformin (MD=-1.11 Mu/L, 95% CI: -6.99-4.77, p=0.71, I²=0%, p=0.69). Pooled analysis demonstrated no significant difference in the risk of nausea (risk ratio (RR)=0.91, 95% CI: 0.53-1.55, P=0.73), although the effect estimate numerically favored liraglutide. The incidence of diarrhea was significantly lower in the liraglutide group compared to metformin. The pooled analysis demonstrated a reduced risk of diarrhea with liraglutide (RR=0.31, 95% CI: 0.12-0.81, P=0.02), suggesting a 69% relative risk reduction as compared to metformin. The available randomized evidence suggests that liraglutide and metformin have comparable effects on BMI, insulin resistance measured by HOMA-IR, fasting glucose, fasting insulin, and menstrual-cycle frequency in women with PMOS. Although both agents have demonstrated clinical benefits in the management of PMOS, the current evidence does not demonstrate a statistically significant advantage of liraglutide over metformin for the assessed outcomes. However, the absence of a statistically significant difference cannot be interpreted as evidence of therapeutic equivalence or non-inferiority, nor does it exclude a clinically meaningful benefit of either treatment.