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Diabet Med. 2003 Sep;20(9):708-12.

Comparative metabolic effects of hydrochlorothiazide and indapamide in hypertensive diabetic patients receiving ACE inhibitor therapy.

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  • 1National Health & Medical Research Council of Australia Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology & Preventive Medicine, Monash University/Alfred Hospital, Prahran, Victoria, Australia.



ACE inhibitors, when used as monotherapy, are frequently unable to adequately control blood pressure in diabetic patients. A diuretic may be added; however, thiazide diuretics, but not indapamide, have been associated with adverse metabolic effects. Whether these effects also apply to thiazides when administered in the currently used lower doses, and whether they differ from indapamide in their metabolic effects, particularly when used in combination with an ACE inhibitor in diabetic patients, has not been previously studied.


We conducted a prospective, randomized, open-label, blinded endpoint crossover study comparing the metabolic responses to the addition of either hydrochlorothiazide (HCTZ) or indapamide, in 18 diabetic hypertensive patients receiving ACE inhibitor monotherapy for hypertension. Patients stabilized on fosinopril 20 mg/day were randomized to receive either HCTZ 12.5 mg od or indapamide 2.5 mg od for 8 weeks, then crossed over to the alternate therapy for a further 8-week period. Blood pressure, heart rate and metabolic assessments were performed at the end of each 8-week treatment period.


Seated and standing systolic and diastolic blood pressures were not different between HCTZ or indapamide when added to fosinopril, nor was the fasting lipid profile or urinary albumin : creatinine ratio. Plasma potassium was lower with indapamide compared with HCTZ treatment (indapamide 4.3+/-0.1 mmol/l; HCTZ 4.5+/-0.1 mmol/l, P<0.01) and HbA1c was higher with indapamide than with HCTZ therapy (indapamide 7.8+/-0.4%; HCTZ 7.2+/-0.3%, P<0.01).


Hydrochlorothiazide 12.5 mg/day, when added to background ACE inhibitor therapy with fosinopril in hypertensive diabetic patients, resulted in a metabolic profile that was similar, if not superior on certain parameters, in comparison with indapamide 2.5 mg/day.

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