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, long-term metformin administration exerts beneficial effects on peripheral insulin sensitivity. Furthermore, this effect disappears at treatment suspension.