The diabetogenic potential of thiazide-type diuretic and beta-blocker combinations in patients with hypertension.

BACKGROUND Recently published trials addressing the pharmacological management of hypertension have reported an increase in new-onset diabetes mellitus when comparing certain older and newer treatment regimens. Thiazide-type diuretics (thiazides) and beta-blockers have been individually implicated, but these drugs are frequently combined, and the magnitude of risk associated with their combined use has not been quantified. METHODS AND RESULTS Randomized control trials were retrieved that: (i) featured stepped treatment to manage hypertension; (ii) compared initial treatment using a thiazide or beta-blocker (older drug) with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker or calcium antagonist (newer drug); (iii) assessed cardiovascular outcomes; (iv) reported new-onset diabetes; and (v) provided at least 1-year follow-up. A meta-analysis of available trials indicated that patients exposed to treatment regimens combining thiazides and beta-blockers are at greater risk of developing diabetes than regimens avoiding this combination of drugs (risk ratio for alternative therapy 0.81, 95% confidence interval 0.77-0.86). Current data cannot inform reliably about the risks associated with individual older drugs because of similar overall exposures in patients starting on newer and older drugs. INTERPRETATION AND IMPLICATIONS The results suggest that the routine combined use of a thiazide with a beta-blocker should be questioned in the early management of hypertension, particularly in patients who are at increased risk of developing new-onset diabetes. In such patients, the increased risk of developing diabetes may exceed the benefit of blood pressure lowering.