Several Antihypertensive Drug Combinations Increase the Risk for Incident Diabetes

Lower systolic blood pressure reduces risk
Value-Based Care in Cardiometabolic Health Dec 2012, Vol 1, No 3 - Cardiometabolic Health
Wayne Kuznar

Los Angeles, CA—Antihypertensive regimens that include a thiazide diuretic or a beta-blocker increase the risk for incident diabetes, according to an observational study presented at the 2012 American Heart Association meeting.

The risk was nearly doubled when both drug classes were used togeth­er compared with antihypertensive combinations that included neither, reported Rhonda Cooper-DeHoff, PharmD, Associate Professor, Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville.

To study the effect of prescribing combined antihypertensive drug classes on diabetes risk, her group conducted a nested case-control study among Kaiser Permanente members (aged 35-65 years) without diabetes at baseline.

Incident diabetes was defined as fasting glucose, ≥126 mg/dL; random glucose, ≥200 mg/dL; hemoglobin A1c, ≥7.0%; or prescription of any diabetes therapy. Ten age-matched controls with a fasting glucose of <126 mg/dL at the time of the case onset of diabetes were selected per case.

A total of 9097 cases of diabetes were matched with 90,495 controls. When drug classes were considered separately, the prescription of a thiazide diuretic “imparted a 50% excess risk of diabetes,” said Dr Cooper-DeHoff. The adjusted odds of developing diabetes increased by 14% with prescription of a beta-blocker. No other drug class was associated with excess risk.

“The diabetes risk for a thiazide diuretic plus beta-blocker combination was stacked, meaning that we saw the full effect of both drugs added together,” she said. This combination increased the adjusted odds of incident diabetes by 87% compared with the nonuse of either of these 2 drug classes.

None of the combinations that included a blocker of the renin-angio­tensin system showed an increased risk for diabetes. “Renin-angiotensin system–blocking combinations may be preferred in patients at high risk of diabetes,” Dr Cooper-DeHoff noted.

A separate analysis that she performed using the database from the Women’s Health Initiative Clinical Trials and Observational Study revealed an increased risk of incident diabetes among postmenopausal women who took ≥2 classes of drugs such as thiazide diuretics, beta-blockers, statins, and antidepressants compared with those who took only a single agent.

Lower Systolic BP Equals Lower Risk of Incident Diabetes
An examination of data from a large, randomized trial comparing outcomes between antihypertensive therapy with the angiotensin receptor blocker losartan and the beta-blocker atenolol among patients with left-ventricular hypertrophy revealed that patients with systolic blood pressure (BP) ≤130 mm Hg had a lower risk of developing diabetes than those with higher in-treatment BPs, reported Peter M. Okin, MD, Director of Clinical Affairs and Associate Director of the Cardiac Graphics Laboratory, Weill Cornell Medical College, New York City.

His analysis of the Losartan Intervention for Endpoint Reduction (LIFE) trial included 7485 patients in the trial without diabetes at baseline. During a mean follow-up of 4.6 years, new-onset diabetes was diagnosed in 520 patients (6.9%).
In a multivariate model, patients with systolic BP ≤130 mm Hg had a significant 38% lower risk of new-onset diabetes compared with those with systolic BP ≥142 mm Hg.

The risk for new-onset type 2 diabetes associated with in-treatment systolic BP of ≤130 mm Hg was
in­dependent of other risk factors for diabetes, notably the previously dem­onstrated decreased risk seen with losartan-based therapy and the in-treatment level of high-density lipoprotein cholesterol, said Dr Okin.

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