Angiotensin receptor blockers and nontraditional health outcomes: an umbrella review of meta‐analyses of randomised controlled trials

AIM: Angiotensin receptor blockers (ARBs) are prescribed for cardiovascular and renal protection, but their effects on nontraditional health outcomes remain unclear. With the increasing use of ARBs in diverse populations, clarifying their broader impact has important clinical implications. METHODS: We conducted an umbrella review of systematic reviews and meta-analyses of randomised controlled trials (RCTs) that assessed ARBs and nontraditional health outcomes. PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to April 2026. Methodological quality was appraised using AMSTAR 2, and certainty of evidence was assessed using GRADE. Where trial-level data were available, we re-analysed outcomes using random-effects models and evaluated heterogeneity, 95% prediction intervals, and small-study effects. RESULTS: Fifteen systematic reviews and meta-analyses of RCTs were included, covering 35 unique nontraditional outcomes. Nine outcomes reached nominal statistical significance, but only a few met more stringent credibility criteria. The most credible associations were lower risks of headache and new-onset diabetes, and lower fasting plasma insulin levels with ARB therapy. Associations with migraine severity, low-density lipoprotein cholesterol, and insulin resistance were suggestive or exploratory because of prediction intervals crossing the null, sparse data, heterogeneity, or limited certainty. No convincing evidence supported associations with oncological, infectious, or transplant-related outcomes. Most included reviews were rated as low or critically low-quality using AMSTAR 2, warranting cautious interpretation. CONCLUSION: ARBs appear to provide therapeutic benefits beyond traditional indications, particularly in metabolic and neurological domains, without evidence of excess harm. These findings may inform clinical decision-making in patients at risk of diabetes or with comorbid pain conditions.