Type 2 diabetes mellitus complicated by hypertension in Japanese patients: switching treatment from high-dose angiotensin II receptor blockers to losartan plus hydrochlorothiazide.

Objective: The aim of the present study was to assess changes in blood pressure and metabolism after switching treatment from maximum-dose angiotensin II receptor blocker (ARB) therapy to a mixture of conventional-dose ARBs and low-dose diuretics.

Methods: This study was conducted among 43 Japanese patients with type 2 diabetes complicated with hypertension in whom continuous treatment with high doses of ARBs did not reduce their blood pressure to the target level (a systolic blood pressure of 130 mmHg or lower and a diastolic blood pressure of 80 mmHg or lower). The antihypertensive and metabolic effects of switching from high-dose ARBs to a combination of losartan (50 mg/day) plus hydrochlorothiazide (12.5 mg/day) were examined. The primary endpoint was a decrease in blood pressure at 24 weeks.

Results: The combination treatment significantly decreased both systolic (baseline: 147±11; 24 weeks: 133±13 mmHg) and diastolic (baseline: 79±8; 24 weeks: 72±10 mmHg) blood pressure. This treatment was also associated with a significant increase in the HbA1c level (baseline: 7.0±0.8%; 24 weeks: 7.2±0.9%) and a significant decrease in the urinary albumin-creatinine ratio (baseline: 280±590; 24 weeks: 110±253 mg/g creatinine). However, the combination treatment had no effect on lipid metabolism or the serum uric acid or potassium levels.

Conclusion: In patients with diabetes, sodium reabsorption in the renal tubules is enhanced, which leads to the development of salt-sensitive hypertension. Therefore, the concurrent use of a diuretic that promotes sodium excretion can increase the antihypertensive effects of other drugs. This study demonstrated that switching from high-dose ARB treatment to losartan/hydrochlorothiazide combination therapy results in significant control of blood pressure.