Insulin sensitizing drugs for weight loss in women of reproductive age who are overweight or obese: systematic review and meta-analysis

Women of reproductive age, who are overweight or obese, are prone to infertility. Weight loss in these women leads to increased fecundity, higher chances of conception after infertility treatment and improved pregnancy outcome. In spite of the advantages, most patients have difficulty in losing weight and often regain lost weight over time. This review assesses whether treatment with insulin sensitizing drugs contributes to weight loss, compared with diet or a lifestyle modification programme. After a systematic search of the literature, only randomized controlled trials (RCTs), investigating the effect of insulin sensitizing drugs on weight loss compared with placebo and diet and/or a lifestyle modification programme, were included. Subjects were restricted to women of reproductive age. The main outcome measure was change in body mass index (BMI). Only 14 trials, unintentionally all but two on women with polycystic ovary syndrome (PCOS) only, were included in the analysis. Treatment with metformin showed a statistically significant decrease in BMI compared with placebo (weighted mean difference, -0.68; 95% CI -1.13 to -0.24). There was some indication of greater effect with high-dose metformin (> 1500 mg/day) and longer duration of therapy (> 8 weeks). Limitations were power, low use of intention-to-treat analysis and heterogeneity of the studies. A structured lifestyle modification programme to achieve weight loss should still be the first line treatment in obese women with or without PCOS. Adequately powered RCTs are required to confirm the findings of this review and to assess whether the addition of high-dose metformin therapy to a structured lifestyle modification programme might contribute to more weight loss.