Antihypertensive drugs reduced risk for new-onset type 2 diabetes; effect varies by antihypertensive class
The results of this individual-patient data meta-analysis suggest that angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers should be first-line antihypertensive agents in patients with prediabetes, an ACP Journal Club commentary said.
An individual-patient data meta-analysis of 19 randomized controlled trials (RCTs) comparing antihypertensive drugs with placebo for primary and secondary prevention found that the effect on new-onset type 2 diabetes differed by class. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) were associated with decreased risk for new-onset type 2 diabetes, beta-blockers and thiazide diuretics were associated with increased risk, and calcium-channel blockers had no apparent significant effect.
The study was published by The Lancet on Nov. 13, 2021. The following commentary by Michael Shannon, MD, FACP, was published in the ACP Journal Club section of Annals of Internal Medicine on April 5.
Without lifestyle changes, 15% to 30% of the almost 100 million Americans with prediabetes (hemoglobin [Hb] A1c, 5.7% to 6.4%) will develop diabetes within 3 to 5 years; this means that approximately 20 million people are at risk. An effective addition to the current methods of diabetes prevention, which comprise lifestyle modifications and metformin, would be welcome.
The U.S. Centers for Disease Control and Prevention estimate that 116 million American adults (47%) have hypertension ([systolic blood pressure] >130 mm Hg or [diastolic blood pressure] >80 mm Hg), and 88 million (35%) have prediabetes. Therefore, it is safe to assume that millions of Americans have both hypertension and prediabetes.
The systematic review and meta-analysis by Nazarzadeh and colleagues found that, in patients who were treated for hypertension, ACE inhibitors and ARBs each reduced risk for new-onset diabetes by 16%, thiazides increased it by 20%, beta-blockers increased it by 48%, and calcium-channel blockers had no effect on risk.
Because only 6.8% (vs. the expected 15% to 30%) of the 145,939 participants developed diabetes during the 4.5 years of follow-up, most participants may have had HbA1c levels in the normal range (≤5.6%) at baseline. Unfortunately, because HbA1c was not routinely reported in the 19 RCTs, prediabetes is not reported in the meta-analysis. The diagnostic criteria for the diagnosis of diabetes were fasting glucose levels, reporting of new-onset diabetes as an adverse event, and International Classification of Diseases, Ninth Revision, codes, so there is no way to know the baseline prevalence of prediabetes.
At a median follow-up of 4.5 years, the absolute risk reduction was 1.19% (number needed to treat, 85) for ACE inhibitors and 0.56% (number needed to treat, 179) for ARBs. However, given the large number of American adults with both hypertension and prediabetes, the potential benefit of antihypertensive drug therapy is great and the take-home message is important.
Current guidelines generally do not include prediabetes as a reason to use a specific drug class for treatment of hypertension but, as has been suggested by others, the results of this analysis suggest that ACE inhibitors or ARBs should be first-line antihypertensive agents in patients with prediabetes.