Clinical relevance of glucose metabolism disturbances induced by antihypertensive drugs

Abstract

Patients with type-2 diabetes mellitus and hypertension are at high risk of cardiovascular disease. Tight blood-pressure control significantly reduces this risk, but is often difficult to achieve. Furthermore, some antihypertensive agents adversely affect glucose and lipid metabolism. The ALPINE (Antihypertensive treatment and Lipid Profile in a North of Sweden Efficacy evaluation) Study compared the metabolic effects of conventional antihypertensive therapy, using a diuretic with a {beta}-blocker as needed, with those of more modern antihypertensive therapy using an AT1-receptor blocker with a calcium antagonist as needed. In this study, 392 patients, most of whom (94%) had never previously been treated with antihypertensive drugs, were randomised to receive hydrochlorothiazide 25 mg alone or with atenolol 50-100 mg, or candesartan cilexetil 16 mg alone or with felodipine extended-release 2.5-5 mg, for 1 year. No cross-over between the randomised treatments was allowed. Most patients needed combination therapy to reach target blood pressure. Hydrochlorothiazidebased treatment significantly increased fasting serum insulin and plasma glucose, compared with candesartan-based treatment, which had no apparent effect on these variables. Triglycerides increased, and high-density lipoprotein cholesterol decreased, to a greater extent with hydrochlorothiazide than with candesartan. Eight hydrochlorothiazide-treated patients developed diabetes, compared with one in the candesartan group (P = 0.03). The incidence of metabolic syndrome was higher in the hydrochlorothiazide group (18 vs. 5, P = 0.007), despite similar blood-pressure reductions. Thus, diuretic and {beta}-blocker-based antihypertensive therapy has an adverse metabolic profile, whereas treatment with an AT1-receptor blocker and a calcium antagonist is metabolically neutral