EFFECTS OF DEXFENFLURAMINE ON GLUCOSE-TURNOVER IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Dexfenfluramine, a serotonin agonist with effects on the central nervo us system (CNS), lowers blood glucose in patients with non-insulin-dep endent mellitus (NIDDM). Previous studies using the hyperinsulinemic c lamp have shown that dexfenfluramine improves insulin action on both s timulation of glucose uptake and inhibition of hepatic glucose product ion (HGP). Since the central nervous system can influence glucose tole rance in ways that may not be detected using a clamp procedure, we inv estigated the effects of dexfenfluramine on glucose kinetics during an oral glucose tolerance test (OGTT) in patients with NIDDM. Glucose ki netics were measured basally and during an OGTT using a double isotope technique and the modified one-pool model of the glucose system. Afte r a 4-week run-in period, studies were performed before, after two 15 mg doses, and then after 4 weeks on 15 mg twice daily in 10 subjects w ith NIDDM. Pasting-plasma glucose was significantly lower after 4 week s on dexfenfluramine (P < 0.01) as was plasma glucose at both 1 and 2 h during the OGTT (P < 0.05). The lower plasma glucose was associated with a reduction in HGP both basally (P < 0.01) and during the 1st hou r of the OGTT (P < 0.05). There was no change in peripheral glucose up take. Plasma insulin levels were unaltered, but plasma glucagon was lo wer after 1 month of treatment. We conclude that dexfenfluramine impro ves fasting-blood plasma glucose and oral glucose tolerance predominan tly by reducing hepatic glucose production.