ACEIs, ARBs decrease new-onset type 2 diabetes in patients with hypertension, CAD, and HF

ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) possess a similar and significant ability to reduce the development of new-onset type 2 diabetes among patients with hypertension, coronary artery disease, and heart failure, according to a meta-analysis study published in Diabetes Care.

Despite the long-term benefits, the drugs do not seem to impact the cardiovascular, cerebrovascular, or mortality outcomes over the short-term, the study authors noted.

The researchers' objective was to study the effects of angiotensin II, which has been shown to increase hepatic glucose production and decrease insulin sensitivity.

The reviewers identified 11 trials covering 66,608 patients. Seven of the trials evaluated patients being treated for hypertension, 2 evaluated patients being treated for coronary disease, and 2 evaluated patients being treated for heart failure. The mean patient age ranged between 53 and 76 years, and greater than half of the participants were men.

In 3 trials, patients in the control group were given placebo. The remaining 8 trials allowed the use of ACEIs or ARBs in the control group. Use ranged from 2% to 23%.

An ACEI or ARB prevented new-onset type 2 diabetes (odds ratio [OR], 0.78; 95% CI, 0.73–0.83). The influence of either an ACEI (6 trials) or an ARB (5 trials) alone on new-onset type 2 diabetes was similar (OR, 0.79; 95% CI, 0.71–0.89 and OR, 0.76; 95% CI, 0.70–0.82, respectively).

Regardless of indication for use-hypertension (7 trials), coronary artery disease (2 trials), or heart failure (2 trials)-reductions in new-onset type 2 diabetes were maintained (OR, 0.79; 95% CI, 0.72–0.85; OR, 0.76; 95% CI, 0.60–0.95; and OR, 0.70; 95% CI, 0.50–0.96; respectively).

"Given our study results, it is clear that blocking the renin-angiotensin system with an ACEI or ARB significantly reduced the odds of developing type 2 diabetes," the authors stated. "It is also clear that the beneficial results will occur regardless of whether ACEIs or ARBs are used."

No statistical heterogeneity was observed for any evaluation (P>.1 for all comparisons). ACEIs and ARBs did not reduce the odds of mortality or cardiovascular or cerebrovascular events versus control therapy among all of the studies combined or the hypertension trials.

"This suggests that hypertension control and not the development of new-onset diabetes drives these end points over the study time period," the authors stated. "It may be that longer-term follow-up is needed to reap the benefits of diabetes prevention or that this factor is not an important determinant of risk in this population."

ACEIs and ARBs reduced the odds of these outcomes among the coronary artery disease studies versus control.

"Given the time frame from onset of diabetes to diabetes-related mortality, cardiovascular or cerebrovascular outcomes, it is difficult to attribute the additional benefits of ACEI or ARB therapy to the development of diabetes alone," the researchers stated.

Although the use of an ACEI or ARB did not prove beneficial in their heart failure analysis, the authors noted that their meta-analysis was made up of only a small fraction of the heart failure trials that have been conducted.

"We limited our meta-analysis to studies that also evaluated new-onset diabetes," they stated. "When evaluating the totality of data in heart failure, ACEIs and ARBs provide a clear mortality benefit in patients with heart failure."

SOURCE Gillespie EL, White CM, Kardas M, Lindberg M, Coleman CI. The impact of ACE inhibitors or angiotensin II type 1 receptor blockers on the development of new-onset type 2 diabetes. Diabetes Care. 2005;28:2261–2266.