Insulin sensitivity after metformin suspension in normal-weight women with polycystic ovary syndrome

Context: To date, the metabolic effects of the long- term metformin administration in anovulatory patients with polycystic ovary syndrome (PCOS) are known, whereas few data are available on the effects of its suspension.Objective: The objective of the study was to evaluate the effects of metformin suspension on insulin sensitivity in PCOS patients.Design: This was a prospective, randomized, placebo-controlled study. Setting: The study was conducted at the University "Magna Graecia" of Catanzaro, Italy.Patients: Patients included 30 normal-weight anovulatory PCOS women and 10 age- and body mass index-matched healthy controls.Intervention: PCOS patients were randomized to receive 1700 mg daily metformin (metformin group) or placebo tables (placebo group) for 12 months, whereas no treatment was administered in healthy women ( control group).Main Outcome Measures: Clinical, endocrine, and metabolic profile and clamp insulin sensitivity index were evaluated at study entry and after 6, 12, 18, and 24 months.Results: At baseline, the clamp insulin sensitivity index resulted significantly different (P < 0.05) in PCOS patients in comparison with healthy controls, without difference between metformin and placebo groups. During treatment, the clamp insulin sensitivity index was significantly improved (P < 0.05) in the metformin group in comparison with baseline and placebo group, without significant differences between the 6- and 12-month assessments. At 6 and 12 months after treatment suspension, in the metformin group, insulin sensitivity index significantly (P < 0.05) worsened in comparison with that observed at baseline and during treatment and with that observed in the placebo and control groups.Conclusion: In normal-weight anovulatory PCOS patients, longterm metformin administration exerts beneficial effects on peripheral insulin sensitivity. Furthermore, this effect disappears at treatment suspension.