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Preventing Thiazide‐Induced Hyperglycemia: Opportunities for Clinical Pharmacists

Thiazide diuretics, as well as the thiazide-like diuretic chlorthalidone, have been recommended as first-line therapy for hypertension for over 30 years. (Both thiazide diuretics and thiazide-like diuretics will be referred to as thiazides in this editorial.) Thiazide use, however, declined in the 1980s and 1990s, mostly due to the drugs’ metabolic effects and the active marketing of newer agents. The Antihypertensive and LipidLowering Treatment to Prevent Heart Attack Trial (ALLHAT) and other trials demonstrated that despite the modest metabolic effects of thiazides, newer agents such as angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, and -blockers were not superior to chlorthalidone. Yet only a minority of antihypertensive regimens include a thiazide, even though the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (published in 2003) recommended the use of thiazides for most patients. In 2004, 26% of patients treated in private practice and 41% treated by the United States Department of Veterans Affairs were prescribed a diuretic. In recent years, one of the most controversial topics in the treatment of hypertension has been the onset of diabetes mellitus after the start of therapy with antihypertensives, especially thiazides. Many clinicians, concerned about the prevalence of diabetes, have advocated against the use of thiazides as initial therapy for hypertension. Until recently, what was largely lost in this discussion was the relationship between hyperglycemia and hypokalemia, which has been well described for over 40 years. 6 This controversy has important implications for clinical pharmacists for a couple of reasons. First, many physicians inappropriately avoid the use of thiazides, contributing to poor blood pressure control. 8 Clinical pharmacists can help optimize therapy for hypertension by over-coming barriers to thiazide use. Second, a recent working group from the National Heart, Lung, and Blood Institute (NHLBI) recommended research to evaluate the mechanism of diuretic-induced hyperglycemia and clinical studies to investigate the prevention of hyperglycemia. Funding may be available for clinical pharmacists who choose to study thiazide-induced hyperglycemia.