Effect of Angiotensin‐Converting Enzyme Inhibitors and Angiotensin II Type 1 Receptor Blockers on the Rate of New‐Onset Diabetes Mellitus: A Review and Pooled Analysis

Abstract

The rising prevalence and health burden of diabetes mellitus require that new approaches for prevention among high-risk populations be evaluated. Emerging evidence from the prospective evaluations of secondary and tertiary outcomes and from retrospective evaluations in randomized controlled trials suggests that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor blockers (ARBs) may reduce the occurrence of new-onset diabetes. Therefore, we each independently searched MEDLINE for randomized controlled trials from January 1966-October 2005 that used an ACE inhibitor or ARB as a primary intervention versus a control group not receiving an ACE inhibitor or ARB and that reported the occurrence of diabetes. Thirteen trials were identified. In each of the 13 studies, the frequency of diabetes in the ACE inhibitor or ARB groups was lower than that in the control groups. In addition, it was consistent in that no study significantly excluded any benefit from ACE inhibitors or ARBs on the rate of new-onset diabetes. The combined occurrence of new-onset diabetes in all 13 studies was 2249 cases among 31,283 patients (7.2%) in the ACE inhibitor or ARB group versus 3230 cases among 35,988 patients (9.0%) in the control group. The combined relative risk of diabetes was 0.80, with a 95% confidence interval of 0.76-0.84, based on a two-sided alpha of 0.05, in favor of ACE inhibitors and ARBs. This observation needs to be confirmed by randomized controlled trials with the frequency of diabetes as the primary prospective end point.

Cytokine Abnormalities in the Etiology of the Cardiometabolic Syndrome

“…Special attention was drawn to RAS inhibition with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers after several studies showed a decreased incidence of new-onset type 2 diabetes mellitus and improvement of cardiovascular disease outcomes [54]. The beneficial effects of RAS inhibition on cardiovascular disease in patients with insulin resistance or overt diabetes may be explained best by the blockade of the pathologic phenomena induced by the activation of RAS: increased oxidative stress; increased vasoconstriction; promotion of a proinflammatory, procoagulatory, and proliferative environment; and the disruption of insulin signaling pathways.…”

Waking up from the DREAM of preventing diabetes with drugs

“…Relative risk of diabetes diagnosis after 1 year of troglitazone was 0.25 (P<0.001), but the effect disappeared in the year after drug discontinuation 12 Angiotensin converting enzyme inhibitors, angiotensin receptor blockers • Systematic reviews of trials in hypertension, heart failure, and coronary disease that assessed diabetes as a secondary or post hoc outcome found large preventive effects 13 • DREAM trial failed to confirm the effect 14 …”

Pharmacological interventions in the prevention of type 2 diabetes

“…Several RCTs were found that met our inclusion criteria [3][4][5][6][7], as well as one Cochrane review [8] and five systematic reviews of RCTs [9][10][11][12][13]. Studies investigating the effects of lifestyle interventions (diet and exercise) were included to enable comparison of non-pharmacological and pharmacological methods of diabetes prevention [14][15][16].…”

“…The effect of the angiotensin-converting enzyme (ACE) inhibitor ramipril on diabetes incidence has been investigated in one RCT [4]; the role of ACE inhibitors and angiotensin receptor blockers (ARBs) in diabetes prevention has been systematically reviewed [10][11][12]. The results of the DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) trial showed that while ramipril did not decrease the progression to diabetes (Table 1), patients receiving ramipril were 16% more likely to regress to normoglycemia compared with placebo recipients (P ¼ 0.001) [4].…”

“…The results of the DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) trial showed that while ramipril did not decrease the progression to diabetes (Table 1), patients receiving ramipril were 16% more likely to regress to normoglycemia compared with placebo recipients (P ¼ 0.001) [4]. In systematic reviews of progression to diabetes in patients with IGT or IFG receiving ACE inhibitors or ARBs (n ¼ 66 608-72 333), the risk of progression to diabetes was reduced by 21-27% and 22-24% in patients receiving ACE inhibitors and ARBs respectively [10][11][12].…”