Improvement of insulin-induced glucose disposal in obese patients with NIDDM after 1-wk treatment with d-fenfluramine.
OBJECTIVE
To study the short-term effects of the serotoninergic anorectic drug d-fenfluramine on insulin-induced glucose disposal.


METHODS
A randomized double-blind placebo-controlled crossover trial with 1-wk treatment periods (2 x 15 mg/day d-fenfluramine) was conducted. Twenty obese subjects, 10 with normal oral glucose tolerance and 10 with non-insulin-dependent diabetes mellitus (NIDDM), were all treated with a weight-maintaining diet. Euglycemic-hyperinsulinemic glucose clamps with measurement of glucose kinetics with D-[3-3H]glucose were performed at either two (patients without NIDDM, 0.05 and 0.10 U.kg-1.h-1) or three (patients with NIDDM, 0.05, 0.10, and 0.50 U.kg-1.h-1) insulin delivery rates.


RESULTS
In the nondiabetic subjects, no significant changes in any metabolic or hormonal parameter were measured in the basal state or during the clamp despite a slight reduction in body weight (-1.2 +/- 0.5 kg, P less than 0.05). In the diabetic patients, no significant changes in body weight or basal plasma insulin levels were observed, but fasting blood glucose levels (8.0 +/- 0.8 vs. 9.4 +/- 1.1 mM, P less than 0.005) and plasma free fatty acid concentrations (1150 +/- 227 vs. 1640 +/- 184 microM, P less than 0.05) were significantly reduced after d-fenfluramine compared with placebo. During the clamp, insulin metabolic clearance rate (MCR) was similar after both placebo and d-fenfluramine; endogenous (hepatic) glucose production was similarly and almost completely suppressed, whereas glucose disposal was remarkably enhanced after d-fenfluramine (average increase of glucose MCR 35 +/- 12%, P less than 0.02).


CONCLUSIONS
Whatever the mechanism(s) involved, a 1-wk treatment with d-fenfluramine induces better blood glucose control and improves insulin sensitivity in obese patients with NIDDM independent of significant weight reduction; this last effect is not present in obese subjects with normal oral glucose tolerance.
Scheen
A J
AJ
Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, Liège, Belgium.
Paolisso
G
G
Salvatore
T
T
Lefèbvre
P J
PJ
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D015992:Body Mass Index; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity
D001786:Blood Glucose; D007328:Insulin; D005277:Fenfluramine