Combination therapy with insulin sensitizers may improve outcomes in overweight patients with polycystic ovary syndrome (PCOS) compared with monotherapy, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

Insulin sensitizers are frequently used to improve insulin sensitivity in patients with PCOS, but it is unclear what effect these drugs have on other aspects of the disease. In a meta-analysis of randomized controlled trials, investigators aimed to evaluate the effects of insulin sensitizers on menstrual frequency, weight loss, sex hormone levels, and metabolic parameters in overweight women with PCOS.

The investigators performed a literature search of the PubMed, EMBASE, Cochrane Library, WanFang Database, WeiPu Database, and China National Knowledge Infrastructure online databases from inception to September 2019 for randomized controlled trials that examined the use of metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, or thiazolidinediones in patients with PCOS.

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Of the 5052 studies identified in the initial search, 14 were selected for analysis. The 619 women who made up the pooled population were from European, American, and Asian countries and ranged in age from 18 to 49 years.

A total of 5 different interventions were used in the studies: metformin, GLP-1 receptor agonists, and thiazolidinediones alone, as well as metformin in combination with GLP-1 receptor agonists or thiazolidinediones.

Compared with metformin alone, metformin in combination with thiazolidinediones resulted in greater menstrual recovery (weighted mean difference [WMD], 4.40; 95% CI, 1.95-9.96), reductions in total testosterone (WMD, -0.37; 95% CI, -0.74 to 0.00), and increases in sex hormone-binding globulin (SHBG; WMD, 4.30; 95% CI, 1.70-6.90).

In a similar fashion, metformin in combination with GLP-1 receptor agonists was superior to metformin alone with regard to reductions in total testosterone (WMD, -0.51; 95% CI, -0.63 to -0.39), increases in SHBG (WMD, 10.90; 95% CI, 7.66-14.14), reductions in androstenedione (WMD, -3.00; 95% CI, -4.99 to -1.01), and decreases in waist circumference (WMD, -6.31; 95% CI, -8.27 to -4.35).

Compared with GLP-1 receptor agonists alone, GLP-1 receptor agonists in combination with metformin resulted in greater reductions in total (WMD, -0.27; 95% CI, -0.48 to -0.06) and free testosterone (WMD, -1.84; 95% CI, -2.95 to -0.73), as well as greater increases in SHBG (WMD, 7.44; 95% CI, 4.82-10.07), reductions in androstenedione (WMD, -2.74; 95% CI, -3.99 to -1.48), and reductions in fasting blood glucose (WMD, -0.40; 95% CI, -0.71 to -0.10).

When used as monotherapy, thiazolidinediones were less effective than metformin for glucose control and improvement of obesity measures.

The researchers noted that the relatively small number of studies included in the analysis and their small sample sizes represented a limitation to the meta-analysis.

The investigators concluded that metformin in combination with GLP-1 receptor agonists or thiazolidinediones may be superior to monotherapy for improvement of hyperandrogenemia and menstrual recovery. “Metformin combined with GLP-1 receptor agonists has additional advantage in improving fasting glucose when compared with GLP-1 receptor agonists alone,” the study authors noted. “[L]arge-scale clinical trials are urgently needed to study different interventions with insulin-sensitive drugs in order to further guide the clinical treatment of women with PCOS.”

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Xing C, Li C, He B. Insulin sensitizers for improving the endocrine and metabolic profile in overweight women with PCOS [published online June 3, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa337