Metformin Is an Efficacious Adjunct to Lifestyle Changes for PCOS Treatment

Metformin in combination with lifestyle modifications is effective for the management of polycystic ovary syndrome (PCOS), according to study findings published in the European Journal of Endocrinology.

Using relevant data from EMBASE, MEDLINE, PsycINFO, ALL EBM, and CINAHL, researchers conducted a systematic review and meta-analysis to determine the effect of metformin in patients with PCOS with insulin sensitivity and a higher body mass index (BMI).

The researchers used a random effects model to perform meta-analyses and stratified patients into subgroups by BMI (<25 kg/m² and ≥25 kg/m²). They also performed the quality appraisal in terms of risk for bias.

Primary outcomes included BMI, homeostatic model assessment of insulin resistance, hirsutism, number of patients with regular menstrual cycles, and duration of menstrual cycles. Noncritical outcomes included weight, fasting glucose, and fasting insulin.

The researchers reviewed a total of 1660 studies, selecting 32 randomized controlled trials and 28 systematic reviews. The included studies varied from low (n=8), to moderate (n=16), to high (n=8) risk for bias.

The researchers used 23 RCTs to study metformin use vs placebo. Compared with patients in the placebo groups, those in the metformin treatment group showed reduced:

• BMIs (mean difference [MD], -0.53; 95% CI, -0.95 to -0.12 kg/m²);
• Insulin resistances (MD, -0.50; 95% CI, -0.91 to -0.09); and
• Menstrual cycle durations (MD, -38.25; 95% CI, -52.77 to -23.74 days).

There were no significant findings in hirsutism or the number of patients with regular menstrual cycles.

Compared with women in the placebo group, those with PCOS and normal weight (BMI <25 kg/m²) showed larger reductions in:

• Waist-hip ratio (MD, -0.01; 95% CI, -0.02 to -0.01);
• Free androgen index (MD, -1.01; 95% CI, -1.72 to -0.29); and
• Androstenedione (MD, -5.40; 95% CI, -8.65 to -2.15 nmol/l).

Women with PCOS and higher BMI (≥25 kg/m²) showed reductions in:

• BMI (MD, -0.89, 95% CI -1.43 to -0.35 kg/m²);
• Fasting glucose (MD, -0.13, 95% CI -0.23 to -0.02 mmol/l);
• Total cholesterol (MD, -0.41, 95% CI -0.68 to -0.14 mmol/l); and
• LDL (MD, -0.35, 95% CI -0.62 to -0.08).

The researchers also compared metformin plus lifestyle interventions with placebo plus lifestyle interventions in 8 RCTs. Compared with patients using placebo with lifestyle changes, those using metformin with lifestyle changes reported a lower BMI (MD, -1.09; 95% CI, -2.12 to -0.06 kg/m²). However, compared with placebo, patients using metformin had more menstrual cycles and mild gastrointestinal side effects (OR, 3.28; 95% CI, 1.64-6.57).

Limitations of this study included a lack of trials on patients with a BMI less than 25 kg/m² and adolescents with PCOS, the exclusion of non-English studies, and low certainty of evidence for some outcomes

According to the researchers, “Metformin should be considered as an efficacious adjunct to lifestyle interventions in adults with PCOS, especially for those with a higher BMI, to improve weight loss, insulin resistance and lipids.”

Disclosures: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Endocrinology Advisor