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.
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.