Comparison of effects of combined ACE inhibitor and low-dose thiazide diuretic with ACE inhibitor alone on insulin action in patients with hypertension and Type 2 diabetes : a double-blind crossover study

Aims  To establish the safety in terms of insulin sensitivity of a low dose thiazide/ACE inhibitor combination. Methods  We examined the effects on insulin sensitivity of captopril either alone or in combination with low-dose bendroflumethiazide (1.25 mg) in 15 hypertensive Type 2 diabetic patients. Insulin action was assessed using an isoglycaemic hyperinsulinaemic clamp in a double-blind, randomised, crossover study after a 6-week placebo run-in and following two 12-week treatment periods with captopril (C) (100 mg) alone or in combination with bendroflumethiazide (CB) (1.25 mg). Results  Blood pressure was lower following CB compare to C (138/83 vs. 144/85 mmHg; P < 0.05) and both were lower than baseline (153/92 mmHg; P < 0.01). CB resulted in a significant increase in fasting plasma glucose compared to C (9.6 ± 2.6 vs. 8.5 ± 1.6 mmol/l; P < 0.05). Exogenous glucose infusion rates required to maintain isoglycaemia during hyperinsulinaemia were lower after CB compared to C (25.1 ± 13.3 vs. 34.2 ± 16.8 µmol/kg/min; P < 0.01) as were isotopically determined glucose utilisation rates (29.0 ± 12.4 vs. 36.6 ± 17.3 µmol/kg/min; P < 0.05). There was no significant difference in fasting endogenous glucose production between treatments (CB 9.3 ± 3.3 vs. C 8.6 ± 1.6 µmol/kg/min), nor between suppression following insulin (CB 4.0 ± 2.1 vs. C 4.3 ± 3.1 µmol/kg/min). Conclusions  Combination of low-dose bendroflumethiazide with captopril lowered blood pressure but resulted in deleterious effects on insulin action compared to captopril alone.