The Antiobesity Effect of GLP-1 Receptor Agonists Alone or in Combination with Metformin in Overweight /Obese Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Abstract

Objectives. Both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metformin (MET) have markedly antiobesity effects in overweight/obese polycystic ovary syndrome (PCOS) patients. However, there was no literature to compare the antiobesity effects of these two medicines. Therefore, a systematic review and meta-analysis were conducted in our present study to evaluate the antiobesity effects of GLP-1RAs either as monotherapy or combined with MET in comparison with MET alone in overweight/obese PCOS patients. Methods. All randomized controlled trials (RCTs) which reported the efficacy of GLP-1RAs and MET in overweight/obese PCOS patients in Medline (from Pubmed), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were independently searched by two reviewers. The random-effect model was used to pool data extracted from the included literature. The weighted mean difference (WMD) and 95% confidence interval (CI) were used to present the meta-analysis results (PROSPERO registration number: CRD42020173199). Results. A total of eight eligible RCTs were finally enrolled in our meta-analysis from the 587 retrieved literature. The results showed that GLP-1RAs alone or combined with MET was associated with a greater weight loss (N = 318, WMD = −2.61, 95% CI: −3.51 to −1.72, P ≤ 0.001 , I2 = 77.5%), more obvious reduction of waist circumference (N = 276, WMD = −3.46, 95% CI: −4.36 to −2.56, P ≤ 0.001 , I2 = 0.0%), and body mass index (BMI) (N = 318, WMD = −0.93, 95% CI: −1.60 to −0.26, P = 0.007 , I2 = 84.9%) in overweight/obese PCOS patients when compared with MET alone. Further sensitivity analysis demonstrated that the meta-analysis results of the efficacy differences in terms of body weight, waist circumference, and BMI were relatively stable and reliable. Conclusion. Our meta-analysis demonstrated that the antiobesity effect of GLP-1RAs alone or combined with MET was superior to MET alone in terms of weight loss, the reduction of waist circumference, and BMI. More large-scale, high-quality RCTs are needed to further confirm these results in PCOS patients.

Anti‐obesity pharmacological agents for polycystic ovary syndrome: A systematic review and meta‐analysis to inform the 2023 international evidence‐based guideline

“…Previous narrative reviews supporting the use of GLP-1 RAs in PCOS focused on single-center RCT and observational studies. 49 Two meta-analyses of GLP-1 RAs versus metformin in PCOS included six and eight RCT studies, respectively, 50,51 which concluded GLP-1 RAs were beneficial with or without metformin for metabolic, reproductive, and anthropometric parameters. However, these analyses combined exenatide and liraglutide in varying protocols and dosing regimens.…”

Therapeutic Potential of Glucagon-like Peptide-1 Agonists in Polycystic Ovary Syndrome: From Current Clinical Evidence to Future Perspectives

“…The following year, another meta-analysis published results focusing on the weight loss effect of GLP-1RAs individually or combined with metformin in overweight/obese women with PCOS. It showed that GLP-1RAs were associated with a more significant effect compared with metformin-only treatment in eight eligible RCTs [ 55 ].…”

Clinical Impact of Glucagon-Like Peptide-1 Receptor Analogs on the Complications of Obesity

“…[122]. By changing the dopaminergic and Women with PCOS, who have overweight or obesity (n = 84) 84 LIRA 1.2 mg alone (n = 21), MET 1000 mg BID + LIRA 1.2 mg combination arm (n = 22), (12-week follow-up) 87 Women with obesity and PCOS (n = 43) 87…”

“…LIRA 1.2 mg was found to be more effective in decreasing BW than MET in subjects with severe obesity and PCOS [ 86 ]. GLP-1 RAs alone or combined with MET compared to MET alone had a better effect in terms of BMI and WC reduction in PCOS patients with overweight and obesity [ 87 ].…”