GOOD METABOLIC AND SAFETY PROFILE OF TROGLITAZONE ALONE AND FOLLOWINGALCOHOL IN NIDDM SUBJECTS

Drinking alcohol is associated with a recognised risk of hypoglycaemia . This double-blind, placebo-controlled study was designed to determin e whether alcohol taken with the evening meal alters the gluco-regulat ory response to troglitazone, (TR), an insulin action enhancer, in non -insulin-dependent diabetes mellitus (NIDDM) subjects to increase the risk of hypoglycaemia. In vitro studies conducted prior to the clinica l study presented here showed no evidence of a pharmacokinetic interac tion between the two drugs. A total of 23, diet-treated, NIDDM subject s received either TR, 200 mg once daily (n = 11) or placebo (PL) (n = 12) for 45 days. On days 42 and 45 subjects were given, on separate da ys, an alcohol challenge (AC), 0.6 mg/kg ethanol in orange juice and a control challenge, CC, orange juice alone, with the evening meal. Ser um glucose, insulin, proinsulin-like molecules, C-peptide and lipids w ere measured during the study, for the 4 h after each challenge and th e following morning (fasting). The over-night urine cortisol/creatinin e ratio (an index of hypoglycaemia) was also determined. For the TR tr eated group, fasting serum glucose the next morning (adjusted geometri c mean: 6.8 mmol/l for CC; 6.7 mmol/l for AC) and weighted mean were n ot statistically significantly different following AC compared to CC. Mean trough glucose for TR after the evening meal was 5.7 mmol/l follo wing both the AC and CC. Analysis of the other parameters showed no sy mptomatic or pharmacodynamic evidence of an acute interaction between TR and alcohol. It can be concluded that occasional drinking of alcoho l, with a meal, by TR-treated NIDDM patients is unlikely to be associa ted with an increased risk of hypoglycaemia. (C) 1997 Elsevier Science Ireland Ltd.