Effects of a Fixed Combination of Losartan With Hydrochlorothiazide on Glucose Tolerance in Hypertensive Patients Uncontrolled with Angiotensin II Receptor Blockers Alone

Abstract

The concomitant use of angiotensin II receptor blocker (ARB) with low doses of hydrochlorothiazide (HCTZ) may provide additional antihypertensive activity. HCTZ induces hypokalemia and hyperglycemia, while ARB slightly induces hyperkalemia. Recently, it has been reported that ARB/ HCTZ did not worsen fasting blood sugar levels; however, the detailed glucose tolerance change effect with combination therapy of ARB/HCTZ compared to ARB alone therapy remains to be investigated. Treated non-diabetes mellitus (DM) hypertensive patients taking a common dose of ARB regimens, not achieving blood pressure (BP) goals, were switched to 50 mg Losartan/12.5 mg HCTZ combinations, and the 75 g oral glucose tolerance test (75 g OGTT) was performed before switching and after switching at 3 months. This study included 30 patients aged 66.5±8.7 years, 67% women. Pre-switching BP 146.6±17.0/ 88.4±10.4 mmHg decreased and was maintained at a steady state, reaching 131.4±1.0/73.8±8.8 mmHg (p<0.001) 3 months later. After switching, blood glucose levels on the 75 g OGTT at fasting, 30, 60 and 120 minutes were significantly decreased. Homeostasis model assessment as an index of insulin resistance and the whole body insulin sensitivity index were significantly ameliorated. On the 75 g OGTT, 50 mg Losartan with 12.5 mg HCTZ combinations did not worsen glucose tolerance; moreover, they improved BP, insulin resistance and sensitivity in non-DM Japanese patients with essential hypertension uncontrolled with ARBs alone.