Good metabolic and safety profile of troglitazone alone and following alcohol in NIDDM subjects.

Drinking alcohol is associated with a recognised risk of hypoglycaemia. This double-blind, placebo-controlled study was designed to determine whether alcohol taken with the evening meal alters the gluco-regulatory 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 clinical study presented here showed no evidence of a pharmacokinetic interaction between the two drugs. A total of 23, diet-treated, NIDDM subjects 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 days, an alcohol challenge (AC), 0.6 mg/kg ethanol in orange juice and a control challenge, CC, orange juice alone, with the evening meal. Serum glucose, insulin, proinsulin-like molecules, C-peptide and lipids were measured during the study, for the 4 h after each challenge and the following morning (fasting). The over-night urine cortisol/creatinine ratio (an index of hypoglycaemia) was also determined. For the TR treated group, fasting serum glucose the next morning (adjusted geometric mean: 6.8 mmol/l for AC) and weighted mean were not statistically significantly different following AC compared to CC. Mean trough glucose for TR after the evening meal was 5.7 mmol/l following both the AC and CC. Analysis of the other parameters showed no symptomatic or pharmacodynamic evidence of an acute interaction between TR and alcohol. It can be concluded that occasional drinking of alcohol, with a meal, by TR-treated NIDDM patients is unlikely to be associated with an increased risk of hypoglycaemia.