{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T11:09:45Z","timestamp":1778929785618,"version":"3.51.4"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diabetic kidney disease (DKD) is a leading cause of chronic and end\u2010stage renal diseases. Sodium\u2010glucose cotransporter\u20102 inhibitors (SGLT2is) and glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) confer renoprotection; however, emerging evidence suggests that combination therapy has synergistic benefits. This meta\u2010analysis evaluated dual versus monotherapy, focusing on the urinary albumin\u2010to\u2010creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). A systematic review and meta\u2010analysis of randomized controlled trials (RCTs) was conducted. PubMed, Scopus, Embase, CINAHL, Medline, and Web of Science were searched until August 2025 for RCTs comparing GLP\u20101RA plus SGLT2i versus monotherapy or placebo in adults with T2D. The primary outcome was the change in UACR, and the secondary outcome was eGFR. Pooled standardized mean differences (SMD) were estimated using random\u2010effects models, including subgroup and sensitivity analyses. Eight RCTs (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091974; sample size, 41\u20134000; follow\u2010up, 16\u2009weeks\u20133.4\u2009years) were included. Combination therapy was well tolerated and significantly reduced UACR compared with monotherapy (SMD \u20130.25, 95% confidence interval (CI) \u20130.38, \u22120.13; I\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090%). The benefits remained significant against SGLT2i alone (SMD, \u22120.28) but not for GLP\u20101RA alone. For eGFR, dual therapy provided a modest benefit versus SGLT2i (SMD 0.12, 95% CI 0.00\u20130.23) but not for GLP\u20101RA. The effects were consistent in patients with DKD and in larger trials. Early SGLT2is and GLP\u20101RA combination therapy is safe and provides superior renoprotection compared to monotherapy in patients with type 2 diabetes, albuminuria, and high cardiorenal risk. Broader adoption of combination therapy could improve outcomes, although cost and access barriers remain an issue.\n                  <\/jats:p>","DOI":"10.1002\/phar.70142","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T06:55:49Z","timestamp":1775631349000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Monotherapy: The Superior Efficacy of Combined\n                    <scp>GLP<\/scp>\n                    \u20101 Receptor Agonist and\n                    <scp>SGLT2<\/scp>\n                    Inhibitors on Renal Biomarkers: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6175-1690","authenticated-orcid":false,"given":"Aya M.","family":"AbdelMagid","sequence":"first","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy Cairo University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3791-5998","authenticated-orcid":false,"given":"Ahmed M.","family":"Kamel","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy Cairo University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6048-847X","authenticated-orcid":false,"given":"Samar F.","family":"Farid","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy Cairo University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-023-05876-w"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201057723\u20106"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2012.10.001"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.10924"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15287"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14410"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32590-X"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30249-9"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.021887"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0588"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci22-0034"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.3683"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2019.06.009"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10157\u2010024\u201002514\u20106"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.10.018"},{"key":"e_1_2_13_18_1","unstructured":"\u201cGetData\u2010Graph\u2010Digitizer.com [Computer Program] \u201d(2008) http:\/\/www.getdata\u2010graph\u2010digitizer.com\/index.php."},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280216669183"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1429"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_13_22_1","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions. 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