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.