Is diabetes still a compelling indication for renin-angiotensin-aldosterone system inhibitors? ============================================================================================== * Robert Fakheri * Sripal Bangalore * Franz Messerli **TO THE EDITOR**: The recent review by Momoniat et al, “ACE inhibitors and ARBs: Managing potassium and renal function,” provides a thorough overview of these important medication classes.1 The authors state, “In general, a renin-angiotensin-aldosterone system inhibitor is recommended if the patient has diabetes; stage 1, 2, or 3 chronic kidney disease; or proteinuria.” The sentence suggests that patients with diabetes alone, even without nephropathy, are to receive renin-angiotensin-aldosterone system inhibitors. We take issue with this statement. The current literature no longer supports the notion that diabetes mellitus is a compelling indication for use of renin-angiotensin-aldosterone system blockers in the absence of associated nephropathy. In a systematic review and meta-analysis of 19 randomized controlled trials that enrolled 25,414 participants with diabetes for a total of 95,910 patient-years of follow-up, we demonstrated that inhibitors of the renin-angiotensin-aldosterone system were not superior to other antihypertensive drug classes in patients with diabetes.2 Specifically, renin-angiotensin-aldosterone system blockers were not superior to thiazides, calcium channel blockers, or beta-blockers at reducing the risk of hard cardiovascular and renal end points.2 Current guidelines from the American Diabetes Association,3 European Society of Cardiology,4 and Joint National Committee5 also do not give preference to these drug classes in patients with diabetes without nephropathy. Perhaps the word “diabetes” could be removed in the above-referenced sentence. Furthermore, heart failure with reduced ejection fraction could be added to the list of conditions that are indications for inhibition of the renin-angiotensin-aldosterone system irrespective of initial blood pressure level. * Copyright © 2020 The Cleveland Clinic Foundation. All Rights Reserved. ## REFERENCES 1. Momoniat T, Ilyas D, Bhandari S. ACE inhibitors and ARBs: Managing potassium and renal function. Cleve Clin J Med 2019; 86(9):601–607. doi:10.3949/ccjm.86a.18024 [Abstract/FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NToiY2Nqb20iO3M6NToicmVzaWQiO3M6ODoiODYvOS82MDEiO3M6NDoiYXRvbSI7czoyMDoiL2Njam9tLzg3LzEvOS4xLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 2. Bangalore S, Fakheri R, Toklu B, Messerli FH. Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and meta-analysis of randomized trials. BMJ 2016; 352:i438. doi:10.1136/bmj.i438 [Abstract/FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjE2OiIzNTIvZmViMTFfNC9pNDM4IjtzOjQ6ImF0b20iO3M6MjA6Ii9jY2pvbS84Ny8xLzkuMS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 3. de Boer IH, Bangalore S, Benetos A, et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care 2017; 40(9):1273–1284. doi:10.2337/dci17-0026 [FREE Full Text](http://www.ccjm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6NzoiZGlhY2FyZSI7czo1OiJyZXNpZCI7czo5OiI0MC85LzEyNzMiO3M6NDoiYXRvbSI7czoyMDoiL2Njam9tLzg3LzEvOS4xLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 4. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018; 39(33):3021–3104. doi:10.1093/eurheartj/ehy339 [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1093/eurheartj/ehy339&link_type=DOI) [PubMed](http://www.ccjm.org/lookup/external-ref?access_num=30165516&link_type=MED&atom=%2Fccjom%2F87%2F1%2F9.1.atom) 5. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014; 311(5):507–520. doi:10.1001/jama.2013.284427 [CrossRef](http://www.ccjm.org/lookup/external-ref?access_num=10.1001/jama.2013.284427&link_type=DOI) [PubMed](http://www.ccjm.org/lookup/external-ref?access_num=24352797&link_type=MED&atom=%2Fccjom%2F87%2F1%2F9.1.atom)