Angiotensin-Converting Enzyme Inhibitors Versus Angiotensin Receptor Blockers for Cardiovascular and Renal Protection in Type 2 Diabetes: A Systematic Review and Meta-Analysis

Type 2 diabetes mellitus (T2DM) increases the risk of cardiovascular morbidity and end-stage renal disease. Renin-angiotensin-aldosterone system (RAAS) inhibitors, specifically angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are standard therapies for organ protection. However, uncertainty remains regarding their comparative efficacy and the safety of combination therapy. This systematic review and meta-analysis aimed to compare the efficacy of ACEIs versus ARBs in reducing cardiovascular and renal events in patients with T2DM and to assess the safety of dual blockade. PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials (RCTs) published up to 2025 comparing ACEIs, ARBs, or their combination against placebo or active controls in T2DM patients. The primary outcome was a composite of cardiovascular death, myocardial infarction, stroke, and renal failure. Methodological quality was assessed using the Cochrane Risk of Bias 2 tool. Data were synthesized using frequentist pairwise and Bayesian network meta-analyses. Heterogeneity was explored via meta-regression, and trial sequential analysis (TSA) was used to assess the sufficiency of evidence. In total, 16 RCTs involving 47,406 participants were included. In pairwise analysis, both ACEIs (risk ratio (RR) = 0.87, 95% confidence interval (CI) = 0.81-0.94) and ARBs (RR = 0.90, 95% CI = 0.83-0.98) significantly reduced the risk of the primary composite endpoint compared to control. Network meta-analysis showed no statistically significant difference between ACEIs and ARBs (RR = 0.98, 95% CI = 0.88-1.09). Although ACEIs ranked slightly higher in probability for reducing all-cause mortality (surface under the cumulative ranking = 78% vs. 65%), this difference was not statistically significant. Dual blockade (ACEI + ARB) increased the risk of hyperkalemia (RR = 2.8) and acute kidney injury (RR = 1.7) without improving efficacy. Meta-regression identified baseline systolic blood pressure as a significant modifier of treatment benefit (p = 0.04). TSA indicated that the evidence for the RAAS blockade's benefit is conclusive. ACEIs and ARBs exhibit comparable efficacy in preventing cardiovascular and renal events in patients with T2DM, with a marginal mortality benefit favoring ACEIs. Dual blockade is associated with increased harm and is not recommended. Monotherapy with either agent remains the preferred strategy for organ protection.