Combination therapy using losartan plus hydrochlorothiazide improves blood pressure control in patients with type 2 diabetes mellitus (T2DM) complicated with hypertension, according to a Japanese study.

The 24-week study recruited 43 Japanese patients with T2DM complicated with treatment-resistant hypertension. Prior to the study, participants were given 12 weeks of continuous treatment with the maximum dosage of angiotensin II receptor blockers (ARBs) as recommended in Japan, but their blood pressure did not reach the target level of systolic ≤130mm Hg and diastolic ≤80mm Hg. [Hypertens Res 2009;32:3-107]

Study participants were assessed for changes in blood pressure and metabolism after switching their treatment plan from maximum dose ARB to a combination of losartan 50 mg/day and hydrochlorothiazide 12.5 mg/day. At the end of the study, participants had significantly lower systolic and diastolic blood pressure. The results also showed that combination therapy did not have any effect on lipid metabolism, serum uric acid and potassium levels. However, HbA1c levels were higher and urinary albumin-creatinine ratios lower, said the researchers. [Intern Med 2014;53:1283-9]

The study found that mean systolic blood pressure dropped from 147±11mmHg at baseline to 133±13 mmHg at the end of the study, while mean diastolic blood pressure fell from 79±8 mmHg to 72±10 mmHg. This significant reduction could be due to the fact that patients with diabetes have enhanced renal tubular reabsorption, leading to the formation of sodium-sensitive hypertension. Diuretics promote sodium excretion, thus increasing the antihypertensive effects of other drugs.

Another explanation for the improved antihypertensive effect is that hydrochlorothiazide probably enhances the antihypertensive effects of ARBs by reducing circulating blood volume and increasing plasma renin activity. As ARBs work by inhibiting the actions of angiotensin II, their effectiveness increases in parallel with plasma renin activity. [J Pharmacol Exp Ther 1990;252:726-32]

Most patients with diabetes complicated by hypertension require multidrug therapy to achieve target blood pressure. Combining a diuretic with ARB and regularly monitoring kidney function, electrolytes and glucose metabolism is a potentially effective option for patients who fail first-line therapy using ARBs. This is particularly apparent in diabetic Japanese patients with treatment-resistant hypertension, summarized the researchers.