Insulin Sensitizers for Improving the Endocrine and Metabolic Profile in Overweight Women With PCOS

Chuan Xing; Chunzhu Li; Bing He


J Clin Endocrinol Metab. 2020;105(9) 

In This Article

Abstract and Introduction


Objective: To evaluate the efficacy of insulin sensitizers on menstrual frequency, sex hormone, and metabolic parameters in overweight women with polycystic ovary syndrome (PCOS).

Methods: We searched multiple databases from inception to September 2019 for randomized controlled trials. Network meta-analysis was conducted using multivariate random effects method.

Results: Fourteen trials reporting on 619 women were included. Compared with metformin, metformin + thiazolidinediones (TZDs) was more superior in menstrual recovery (weighted mean difference [WMD] 3.68; 95% credibility interval [CrI], 1.65 to 8.20), metformin + glucagon-like peptide-1 (GLP-1) receptor agonists was more effective in decreasing androstenedione (WMD −2.53; 95% CrI, −3.96 to −1.09), both metformin + GLP-1 receptor agonists (WMD 9.22; 95% CrI, 5.46 to 12.98) and metformin + TZDs (WMD 4.30; 95% CrI, 0.78 to 7.82) were more effective in increasing sex hormone–binding globulin (SHBG), while TZDs were less effective in decreasing body mass index (BMI) (WMD 1.69; 95% CrI, 0.72 to 2.66). Compared with GLP-1 receptor agonists, metformin + GLP-1 receptor agonists was associated with higher SHBG (WMD 7.80; 95% CrI, 4.75 to 10.85), lower free testosterone (WMD −1.77; 95% CrI, −3.25 to −0.29), lower androstenedione (WMD −2.70; 95% CrI, −3.91 to −1.50) and lower fasting blood glucose (WMD −0.41; 95% CrI, −0.73 to −0.08).

Conclusion: For overweight women with PCOS, both metformin combined with GLP-1 receptor agonists and metformin combined with TZDs appear superior to monotherapy in improving hyperandrogenemia. Metformin combined with TZDs could be particularly effective in promoting the recovery of menstruation. Metformin combined with GLP-1 receptor agonists has the additional advantage of improving fasting glucose when compared with GLP-1 receptor agonists alone. TZDs are inferior to metformin in decreasing BMI.


Polycystic ovary syndrome (PCOS) is characterized by oligoovulation or anovulation, elevated androgen production, and polycystic ovary changes observed by ultrasound. PCOS affects up to 13% of women of reproductive age.[1] The pathogenesis of PCOS is far from completely clear and may relate to hyperandrogenemia, hyperinsulinemia, an imbalanced ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH), metabolic aberrances, inflammation, advanced glycation end products, and endoplasmic reticulum stress.[2–5] PCOS is often accompanied by obesity and increased rates of type 2 and gestational diabetes, cardiovascular disease, hepatic steatosis, and endometrial cancer, which, as long-term risks, can lead to serious threats to a woman's life.[6–9] Overweight women with PCOS are more prone to insulin resistance, which could lead to abnormal glucose and lipid metabolism.[10] Moreover, hyperinsulinemia reduces the circulating level of sex hormone-binding globulin (SHBG) and increases free testosterone (FT), which inhibits follicular maturation with consequent menstrual irregularity and infertility.[11]

Currently, symptomatic treatment dominates the clinical approach to PCOS and mainly includes the regulation of menstrual cycle, anti-hyperandrogenemia therapy, weight control, management of insulin resistance and metabolic disorders, and lifestyle modification.[12–14] Drugs often used to reduce insulin resistance in obese patients with PCOS include metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, and thiazolidinediones (TZDs).[7] However, the efficacy of different interventions on metabolism for PCOS remains to be verified. For this reason, we designed this meta-analysis to compare the effects of these drugs on the improvement of menstrual frequency, as well as sex hormone and metabolic parameters, of overweight women with PCOS. In addition, we searched for eligible interventions that can reduce hyperinsulinemia and induce weight loss in PCOS.