{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:09:56Z","timestamp":1792091396456,"version":"4.4.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp; Metabol"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>It is uncertain if the combination of sodium\u2010glucose co\u2010transporter 2 inhibitors (SGLT2\u2010Is) and renin\u2010angiotensin\u2010aldosterone system inhibitors (RAAS\u2010Is) provides better cardio\u2010renal clinical outcomes in people with type 2 diabetes mellitus (T2DM) compared with SGLT2\u2010Is alone. Using a systematic review and meta\u2010analysis of randomized controlled trials (RCTs), we evaluated the efficacy and safety with respect to cardio\u2010renal outcomes of the combination of SGLT2 and RAAS inhibitors\u00a0vs SGLT2\u2010Is in patients with T2DM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Studies were identified from MEDLINE, Embase, the Cochrane Library and search of bibliographies to May 2021. The Cochrane risk of bias tool was used to assess the risk of bias of each study. Study\u2010specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. Quality of the evidence was assessed using GRADE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nine articles comprising 8 RCT evaluations (<jats:italic>n<\/jats:italic>\u00a0=\u00a034,551 participants) that compared SGLT2\u2010Is with placebo in patients with T2DM against a background of standard care and reported subgroup results for those treated with or without RAAS\u2010Is at baseline were included. No RCT specifically investigated the combination of SGLT2 and RAAS inhibitors compared with SGLT2\u2010Is alone. The RRs (95% CIs) for composite cardiovascular outcome and composite CVD death\/heart failure hospitalization comparing SGLT2\u2010Is vs placebo in patients on RAAS\u2010Is were 0.93 (0.85\u20131.01) and 0.88 (0.76\u20131.02), respectively. The corresponding estimates for patients not on RAAS\u2010Is were 0.78 (0.65\u20130.93) and 0.73 (0.65\u20130.82), respectively. There was no evidence of interactions between RAAS\u2010I status and the effects of SGLT2\u2010Is for both outcomes. Single study results showed that SGLT2\u2010Is vs placebo reduced the risk of composite kidney outcome and cardiovascular death in patients with RAAS inhibition. The effect of SGLT2 inhibition vs placebo on kidney parameters, genital infections, volume depletion, hyperkalaemia, hypokalaemia, hypoglycaemia and other adverse events was similar in patients with or without RAAS inhibition. The quality of the evidence ranged from very low to moderate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Aggregate published data suggest that the combination of SGLT2 and RAAS inhibitors\u00a0in the treatment of patients with T2DM may be similar in efficacy and safety if not superior to SGLT2\u2010Is alone. Head\u2010to\u2010head comparisons of the two interventions are warranted to inform T2DM management. The use of SGLT2 inhibition as a first\u2010line therapy in T2DM or its early use in the prevention of renal deterioration and cardiovascular complications in addition to its glycaemic control deserves further study.<\/jats:p><\/jats:sec>","DOI":"10.1002\/edm2.303","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T19:19:50Z","timestamp":1634325590000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Benefits and harms of sodium\u2010glucose co\u2010transporter\u20102 inhibitors (SGLT2\u2010I) and renin\u2013angiotensin\u2013aldosterone system inhibitors (RAAS\u2010I) versus SGLT2\u2010Is alone in patients with type 2 diabetes: A systematic review and meta\u2010analysis of randomized controlled trials"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8335-7018","authenticated-orcid":false,"given":"Samuel","family":"Seidu","sequence":"first","affiliation":[{"name":"Diabetes Research Centre University of Leicester Leicester General Hospital Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2625-0273","authenticated-orcid":false,"given":"Setor K","family":"Kunutsor","sequence":"additional","affiliation":[{"name":"National Institute for Health Research Bristol Biomedical Research Centre University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol Bristol UK"},{"name":"Translational Health Sciences Bristol Medical School Learning &amp; Research Building (Level 1) University of Bristol Southmead Hospital Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinar","family":"Topsever","sequence":"additional","affiliation":[{"name":"Department of Family Medicine Acibadem Mehmet Ali Aydinlar University School of Medicine Kerem Aydinlar Campus Atasehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamlesh","family":"Khunti","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre University of Leicester Leicester General Hospital Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30058-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40273-015-0268-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31678-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.7.1813"},{"key":"e_1_2_9_6_1","unstructured":"WHO Health Topics.Diabetes.https:\/\/www.who.int\/health\u2010topics\/diabetes#tab\u00a0=\u00a0tab_1. 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