Anti Hypertensive Medications Thiazides

Thiazides have been associated with glycemic disturbance for many decades. In 1981, a randomized, controlled trial from the Medical Research Council suggested that patients receiving bendrofluazide developed more impaired glucose tolerance (IGT) than those receiving propranolol (15.4 vs. 4.8 cases patient-years, respectively) (13). This study was criticized for using extremely high dose of bendrofluazide. There are, however, many prospective clinical trials that have demonstrated definite adverse effects of thiazide diuretics on glucose homeostasis (14). In a post hoc analysis of the Systolic Hypertension in the Elderly Program (SHEP) trial, 3 years of low-dose chlorthalidone was associated with a significant elevation in fasting glucose compared to placebo (0.51 mmol/L vs. 0.31 mmol/L, respectively; P< 0.01) (15). This trail also demonstrated a clinically significant increase in the incidence of diabetes (13% vs. 8.7%, respectively; P< 0.001). In anti-hypertensive and lipid-lowering treatment to prevent Heart Attack Trial (ALLHAT), over 42,000 hypertensive patients received chlorthalidone, amlodipine, lisinopril or doxazosin as treatment for control of blood pressure. After 4 years, the incidence of diabetes was significantly higher in the chlorthalidone group (11.6%) than other treatment groups; amlodipine (9.8%) and lisinopril (8.1%) (16).

It is logical to conclude that diuretics appear to have a dose-dependent unfavorable effect on glycemic control, which may not be apparent, in short term. There are multiple mechanisms through which thiazide diuretics may worsen glycemic control. The hypokalemic effect of diuretics may blunt the release of insulin from the pancreas (17), elevations in fatty

TABLE 1 Drugs With Potential Adverse Effects on Glucose Homeostasis

Anti-hypertensive drugs Thiazide diuretics Beta-blockers Calcium-channel blockers Minoxidil Diazoxide Alpha-agonist Lipid-lowering agents Niacin

Beta adrenoreceptor agonists

Corticosteroids Immunosupressive and immune modulating drugs Tacrolimus Cyclosporine Interleukins Thyroid hormones Growth hormone Oral contraceptives Drugs for HIV treatment Psychiatric agents Miscellaneous Glucosamine sulphate Interferon Phenytoin Lithium acids and lipids as a result of their use can cause hyperglycemia (18). Other mechanisms that may result in hyperglycemia include decreased insulin sensitivity (19), increased hepatic glucose production (20), a direct inhibitory effect on insulin secretion (21) and enhanced catecholamine secretion and action (22).

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