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Case reports suggesting that co\u2010administration of insulin secretagogues with ACEIs is associated with an increased risk of serious hypoglycemia have led to warnings regarding a drug\u2013drug interaction in widely used drug compendia. However, subsequent studies have had inconsistent results. We performed a systematic review to evaluate the evidence that concomitant use of ACEIs and insulin secretagogues increases the risk of serious hypoglycemia. MEDLINE\/PubMed and Embase were searched from inception to July 2023 for studies evaluating adults with T2D treated with insulin secretagogues, such as sulfonylureas or meglitinides, and exposed to an ACEI. The primary outcome was serious hypoglycemia. A literature search yielded 472 papers, of which five met the inclusion criteria. The heterogeneity of the studies precluded meta\u2010analysis. Two studies using multiple methods to address bias found no association between hypoglycemia and concomitant use of ACEI and insulin secretagogues. Three studies found potential associations, but only one was statistically significant; these studies were at serious or critical risk of bias due to potential confounding from lack of adjustment for renal dysfunction. The higher quality studies found no association between the concomitant use of insulin secretagogues with ACEI and hypoglycemia. Drug compendia and electronic health records should consider updating and removing alerts warning of a drug\u2013drug interaction between insulin secretagogues as a class and ACEIs.<\/jats:p>","DOI":"10.1002\/cpt.3530","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T06:15:40Z","timestamp":1734070540000},"page":"1005-1011","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Risk of Hypoglycemia Associated With Concomitant Use of Insulin Secretagogues and ACE Inhibitors in Adults With Type 2 Diabetes: A Systematic Review"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4633-1716","authenticated-orcid":false,"given":"Patricia Y.","family":"Chu","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology &amp; Diabetes, Department of Pediatrics Children's Hospital of Philadelphia  Pennsylvania Philadelphia USA"},{"name":"Division of Endocrinology, Diabetes &amp; Metabolism, Department of Medicine, Department of Medicine University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Center for Real\u2010World Effectiveness and Safety of Therapeutics, Center for Clinical Epidemiology and Biostatistics, and Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6345-5852","authenticated-orcid":false,"given":"Emma K.","family":"Edmondson","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes &amp; Metabolism, Department of Medicine, Department of Medicine University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0259-969X","authenticated-orcid":false,"given":"James H.","family":"Flory","sequence":"additional","affiliation":[{"name":"Endocrinology Service, Department of Subspecialty Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4726-9413","authenticated-orcid":false,"given":"Sean","family":"Hennessy","sequence":"additional","affiliation":[{"name":"Center for Real\u2010World Effectiveness and Safety of Therapeutics, Center for Clinical Epidemiology and Biostatistics, and Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,13]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30025-1"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1185\/030079902125000200"},{"key":"e_1_2_10_3_1","volume-title":"Shivkumar A","author":"Costello R.A.","year":"2023"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.460"},{"key":"e_1_2_10_5_1","volume-title":"Angiotensin converting enzyme inhibitors (ACEI)","author":"Herman L.L."},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199311113292004"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfad118"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(90)90227-5"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-020-0518-5"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198812153192416"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)92148-6"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)92148-6"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)92148-6"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/amiajnl-2012-001089"},{"key":"e_1_2_10_15_1","unstructured":"Micromedex\u00ae (electronic version).IBM Watson Health GV Colorado USA<https:\/\/www.micromedexsolutions.com>. 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