Effect of dose escalation of metformin on clinical features, insulin sensitivity and androgen profile in polycystic ovary syndrome

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Objective The benefit of metformin on polycystic ovary syndrome (PCOS) has been debated. Varying results have been observed in different studies which could be due to differences in the study cohorts and the heterogeneity of the syndrome. We hypothesized that the dose of metformin generally used may not be adequate for women with higher BMI and observed the effect of dose escalation on PCOS in women with differing BMI and baseline insulin resistance. Study design Forty women were recruited to the study. Patients were started on 1 g/day and increased every 8 weeks by 1–3 g at the end of 16 weeks. The study was carried out for 24 weeks. Analysis was carried out based on BMI and baseline insulin sensitivity. There were four groups based on BMI with 10 patients in each group (groups A: 18–24.9 kg/m 2, B: 25–29.9 kg/m 2, C: 30–34.9 kg/m 2 and D: 35–40 kg/m 2). There were three tertiles based on insulin sensitivity. In order of insulin resistance, tertile 1 ( n = 13) – high insulin resistance (IR), tertile 2 ( n = 13) – mid IR, tertile 3 ( n = 14) – low IR. The outcome measures were clinical features, insulin sensitivity and androgens. Results A trend towards reduction of fasting insulin concentration was observed which reached statistical significance ( p < 0.05) in group D. At the highest dose of 3 g, groups B and C also showed a decrease in insulin concentrations but statistical significance was not achieved. On examination of changes in insulin resistance over time, groups B, C and D showed a trend towards improvement in sensitivity but QUICKI remained below 0.333. No definite benefit from higher doses was seen. When analyzed based on the three tertiles, there was significant drop in fasting insulin concentration in the first tertile (−16.73 ± 9.8 nmol/L). Measurement of QUICKI also revealed a significant improvement in the first tertile ( p = 0.001). Conclusion There is no benefit from increased doses of metformin in PCOS but reduction of insulin resistance is more significant in those patients with a lower insulin sensitivity at baseline.