Systemic hypertension-review
A Meta-Analysis of 94,492 Patients With Hypertension Treated With Beta Blockers to Determine the Risk of New-Onset Diabetes Mellitus

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Beta blockers used for the treatment of hypertension may be associated with increased risk for new-onset diabetes mellitus (DM). A search of Medline, PubMed, and EMBASE was conducted for randomized controlled trials of patients taking β blockers as first-line therapy for hypertension with data on new-onset DM and follow-up for ≥1 year. Twelve studies evaluating 94,492 patients fulfilled the inclusion criteria. Beta-blocker therapy resulted in a 22% increased risk for new-onset DM (relative risk 1.22, 95% confidence interval [CI] 1.12 to 1.33) compared with nondiuretic antihypertensive agents. A higher baseline fasting glucose level (odds ratio [OR] 1.01, 95% CI 1.00 to 1.02, p = 0.004) and greater systolic (OR 1.05, 95% CI 1.05 to 1.08, p = 0.001) and diastolic (OR 1.06, 95% CI 1.01 to 1.10, p = 0.011) blood pressure differences between the 2 treatment modalities were significant univariate predictors of new-onset DM. Multivariate meta-regression analysis showed that a higher baseline body mass index (OR 1.17, 95% CI 1.01 to 1.33, p = 0.034) was a significant predictor of new-onset DM. The risk for DM was greater with atenolol, in the elderly, and in studies in which β blockers were less efficacious antihypertensive agents and increased exponentially with increased duration on β blockers. For the secondary end points, β blockers resulted in a 15% increased risk for stroke, with no benefit for the end point of death or myocardial infarction. In conclusion, β blockers are associated with an increased risk for new-onset DM, with no benefit for the end point of death or myocardial infarction and with a 15% increased risk for stroke compared with other agents. This risk was greater in patients with higher baseline body mass indexes and higher baseline fasting glucose levels and in studies in which β blockers were less efficacious antihypertensive agents compared with other treatments.

Section snippets

Study selection

We conducted a search of studies on Medline, PubMed, and EMBASE using the terms: “β adrenergic blockers,” “adrenergic β antagonist,” “β blockers,” and “hypertension.” We limited our search to studies in human subjects published in English in peer-reviewed journals from 1966 to March 2007. We included only randomized controlled studies with randomized comparisons of regimens based on β blockers with those using other agents, with follow-up of ≥1 year, and evaluating the occurrence of new-onset

Study selection

Of the 805 randomized controlled trials of β blockers in patients with hypertension, 12 studies evaluating 94,492 patients fulfilled the inclusion criteria (Figure 1,Table 1, Table 2, Table 3). We excluded the results of the Metoprolol Atherosclerosis in Hypertension (MAPHY) trial19 because this was a subgroup analysis from the Heart Attack Primary Prevention in Hypertension (HAPPHY) trial.20 Similarly, we excluded the results of the Systolic Hypertension in the Elderly (SHEP) study,21 the

Discussion

The results of the present meta-analysis show that β-blocker therapy for hypertension is associated with increased risk for new-onset DM compared with nondiuretic antihypertensive drugs and also compared with placebo. This excess risk was greater in the cohort aged ≥60 years, in the cohort with higher baseline fasting glucose levels and higher baseline BMIs, and when the systolic blood pressure difference between the 2 treatment groups at study end was greater. The results of this analysis let

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