Fluoxetine improves insulin sensitivity in obese patients with non-insulin-dependent diabetes mellitus independently of weight loss

OBJECTIVE: To study the effect of fluoxetine, a specific serotonin reuptake inhibitor, on insulin sensitivity in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) independently of its action on body weight. RESEARCH DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled trial, insulin-mediated glucose disposal was measured in 12 obese patients with NIDDM on diet alone before and after four weeks of treatment with either placebo (n=6) or fluoxetine (n=6) at a dose level of 60 mg once a day. insulin-mediated glucose disposal was assessed by the 2-step euglycemic hyperinsulinemic clamp technique. Patients were instructed on a weight-maintaining diet. RESULTS: Insulin infusion at 40 mU . m(-2). min(-1) resulted in insulin levels of 720+/-70 pmol . L(-1) with a mean plasma glucose value of 6.4+/-0.2 mmol . L(-1). Compared to placebo, fluoxetine increased glucose disposal (M) by 2.4-fold (P < 0.05), the insulin sensitivity index (M/I) by 2.7-fold (P < 0.03) and the glucose metabolic clearance rate (MCR) by 2.9-fold (P < 0.03). Insulin infusion at 400 mU . m(-2). min(-1) elicited insulin levels of 12947+/-1512 pmol . L(-1) with a mean plasma glucose value of 5.6+/-0.4 mmol . L(-1). Compared to placebo, fluoxetine increased M by 30% (P=NS), M/I by 40% (P < 0.04) and MCR by 23% (P < 0.04). Patient weight remained stable throughout the study with no change in dietary intake. CONCLUSION: Fluoxetine improves insulin-mediated glucose disposal in obese patients with NIDDM independently of weight loss.