Antihypertensive drugs linked to differential risk for diabetes

AII receptor antagonists or ACE inhibitors are least associated with incident diabetes.

Issue: March 2007

Hypertension treatment with angiotensin II receptor antagonists and ACE inhibitors is least likely to lead to diabetes; however, diuretics or beta-blockers increase a patient’s chance of developing diabetes, according to a report published in The Lancet.

“We should monitor our patients for the development of diabetes, and we should remain cognizant that different medicines have different propensities. But we should use all the medicines necessary to get and keep blood pressure under control,” said William J. Elliott, MD, PhD, professor of preventive medicine, internal medicine and pharmacology at Rush Medical College of Rush University Medical Center, Chicago.

Several long-term clinical trials have shown that patients on antihypertension medications are more likely to have reduced glucose tolerance and precipitated new-onset diabetes than those without hypertension. This is often attributed to increased weight, recent weight gain or stronger family history of diabetes among those with hypertension.

Elliott and colleagues analyzed data to assess the relationship between long-term treatment with classes of antihypertensive drugs and incident diabetes.

Evaluating a relationship

The researchers conducted a network meta-analysis of long-term, randomized clinical trials from 1966 to 2006 among 143,153 participants who did not have diabetes at randomization. They identified 22 clinical trials of each class of antihypertensive drugs. They assessed the chance that a person would develop diabetes during one to about five years of observation.

Their findings showed that the lowest risk for new-onset diabetes occurred with AII receptor antagonists (OR=0.57; 95% CI, 0.46-0.72), which were better but not significantly better than ACE inhibitors (OR=0.67; 95% CI, 0.56-0.80) followed by calcium channel blockers (OR=0.75; 95% CI, 0.62-0.90) and placebo (OR=0.77; 95% CI, 0.63-0.94). The risk was highest with diuretics and beta-blockers (OR=0.90; 95% CI, 0.75-1.09), according to Elliott. Compared with placebo, diuretics or beta-blockers slightly but significantly increased the risk for developing diabetes. AII receptor antagonists or ACE inhibitors significantly decreased the risk. These findings suggest that the differences between antihypertensive drugs and the risk for new-onset diabetes are real and significant.

“Don’t throw out the blood pressure medicines because you are worried about the risk for getting diabetes; instead, monitor patients,” Elliott advised. “It is certainly important when you find out a patient has diabetes because it changes their blood pressure target and their cholesterol target, and they probably ought to always be on aspirin after that.”

Franz H. Messerli, MD, said this meta-analysis is “thorough and comprehensive, corroborating and extending previous work from our group and other investigators.

“It provides a clinically useful document on the diabetogenic properties – or absence thereof – of various antihypertensive drug classes,” said Messerli, director of the hypertension program, division of cardiology at St. Luke’s-Roosevelt Hospital, New York.

In the United States, the 2003 national hypertension guidelines recommend diuretics as first-line treatment and beta-blockers as only one of several acceptable second-line options. Last June the British National Institute for Health and Clinical Excellence issued a new set of guidelines, based on economic considerations, which recommended against using both a diuretic and a beta-blocker for the routine treatment of hypertension.

The findings of this study showed that the risk for new-onset diabetes with beta-blockers and diuretics appears to be small, according to Messerli. However, in the United States, about 20 million people are taking thiazide diuretics and almost the same numbers are prescribed beta-blockers. On average, about 7% to 8% of patients on antihypertensive drugs develop diabetes, which doubles the risk for CV events.

“By using blockers of the renin-angiotensin system or calcium antagonists instead of beta-blockers and diuretics, a substantial number of new-onset diabetes could possibly be prevented,” Messerli said. –by Tara Grassia

This article also appeared in Today in Cardiology, a SLACK Incorporated publication.

For more information:
Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007;369:201-207.