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

Abstract

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 12 947±1 512 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.