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.


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.


CONCLUSIONS
Fluoxetine improves insulin-mediated glucose disposal in obese patients with NIDDM independently of weight loss.
Maheux
P
P
Clinical Research Institute of Montreal, Department of Medicine, Faculty of Medicine, University of Montreal, Canada.
Ducros
F
F
Bourque
J
J
Garon
J
J
Chiasson
J L
JL
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000627:therapeutic use*; D015309:Glucose Clamp Technique; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects
D001786:Blood Glucose; D005473:Fluoxetine; D007328:Insulin; D017367:Selective Serotonin Reuptake Inhibitors