{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:55:15Z","timestamp":1790567715959,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Individually, sodium\u2013glucose co\u2010transporter\u20102 inhibitors (SGLT2i) and glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) have been shown to reduce major kidney and cardiovascular events in patients with chronic kidney disease (CKD). However, evidence supporting combined GLP\u20101RA and SGLT2i therapy in this population remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, including adults with CKD treated with SGLT2i alone or SGLT2i with subsequent initiation of GLP\u20101RA between June 2020 and December 2023. Propensity score matching (1:1) adjusted for demographics, comorbidities, medications, and laboratory values. The primary outcome was major adverse kidney events (MAKE); secondary outcomes included all\u2010cause mortality and major adverse cardiovascular events (MACE). Time\u2010to\u2010event analyses were performed using Cox proportional hazards models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 112\u2009596 patients with CKD, 16460 received SGLT2i and GLP\u20101RA combination therapy, and 96\u2009136 received SGLT2i monotherapy. The matched cohort included 32\u2009448 patients (16\u2009224 per group). Over a median follow\u2010up of 12\u2009months, the addition of a GLP\u20101RA was associated with lower rates of the primary outcome of MAKE (HR 0.70; 95% CI 0.65\u20130.74;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) compared with SGLT2i monotherapy. Combination therapy was also associated with lower risks of MACE (HR 0.83; 95% CI 0.78\u20130.87) and all\u2010cause mortality (HR 0.55; 95% CI 0.50\u20130.61). Benefits were consistent across CKD stages and diabetes status, with significantly more pronounced effects observed in patients with obesity, heart failure, and ischemic heart disease. Combination therapy was associated with increased gastrointestinal symptoms, genital infections, and retinopathy progression, but lower risks of volume\u2010depletion events and acute kidney injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this real\u2010world CKD cohort, GLP\u20101RA added to SGLT2i therapy was associated with substantial incremental reductions in kidney disease progression and cardiovascular events. These findings suggest an additive cardiorenal benefit, particularly in patients with obesity, supporting the evaluation of combination therapy in future randomised trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71375","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:03:21Z","timestamp":1790564601000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effectiveness of Adding\n                    <scp>GLP<\/scp>\n                    \u20101 Receptor Agonists to\n                    <scp>SGLT2<\/scp>\n                    Inhibitor Therapy in Chronic Kidney Disease: A Population Based Study"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4759-1540","authenticated-orcid":false,"given":"Hussain","family":"Salim","sequence":"first","affiliation":[{"name":"Department of Medicine Dow University of Health Sciences  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaheer","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Department of Medicine Dow University of Health Sciences  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav S.","family":"Gulsin","sequence":"additional","affiliation":[{"name":"National Institute of Health and Care Research, Leicester Biomedical Research Centre Glenfield Hospital  Leicester UK"},{"name":"Department of Cardiovascular Sciences, British Heart Foundation Cardiovascular Research Centre University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habib R.","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Schulich School of Medicine and Dentistry Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9051-6081","authenticated-orcid":false,"given":"Saad Ahmed","family":"Waqas","sequence":"additional","affiliation":[{"name":"Department of Medicine Dow University of Health Sciences  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerry P.","family":"McCann","sequence":"additional","affiliation":[{"name":"National Institute of Health and Care Research, Leicester Biomedical Research Centre Glenfield Hospital  Leicester UK"},{"name":"Department of Cardiovascular Sciences, British Heart Foundation Cardiovascular Research Centre University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Garg","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Schulich School of Medicine and Dentistry Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Shurrab","sequence":"additional","affiliation":[{"name":"Cardiology Department Health Sciences North, Northern Ontario School of Medicine University  Sudbury Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamlesh","family":"Khunti","sequence":"additional","affiliation":[{"name":"National Institute of Health and Care Research, Leicester Biomedical Research Centre Glenfield Hospital  Leicester UK"},{"name":"Diabetes Research Centre University of Leicester  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Rashid","sequence":"additional","affiliation":[{"name":"National Institute of Health and Care Research, Leicester Biomedical Research Centre Glenfield Hospital  Leicester UK"},{"name":"Department of Cardiovascular Sciences, British Heart Foundation Cardiovascular Research Centre University of Leicester  Leicester UK"},{"name":"Diabetes Research Centre University of Leicester  Leicester UK"},{"name":"Keele Cardiovascular Research Group, Centre for Prognosis Research, School of Medicine Keele University  Keele UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2024.03.020"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050686"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dci22\u20100027"},{"key":"e_1_2_12_5_1","unstructured":"KDIGO \u201cDiabetes in CKD \u201daccessed December 10 2025 https:\/\/kdigo.org\/guidelines\/diabetes\u2010ckd\/."},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024816"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204233"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603827"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607141"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2108269"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)31149\u20103"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2403347"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010023\u201001798\u20104"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1358573"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2023.05.048"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/jamiaopen\/ooad035"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.4103\/sja.SJA_543_18"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfaf064"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.10.018"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1516126"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.645563"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2019.10.029"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201050199\u2010y"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2016\u20100198"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.7326\/M16\u20102607"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfae396"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph18081130"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010024\u201002090\u20109"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892\u2010018\u20101011\u20107"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2023.11.007"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.30952"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcjd.2019.09.003"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2024.101594"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557\u2010022\u201007360\u2010w"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741\u2010025\u201010523\u20100"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00392\u2010023\u201002362\u20106"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010021\u201001385\u20105"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.15277\/bjd.2021.301"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18\u20101355"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1590\/2175\u20108239\u2010JBN\u20102020\u20100100"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.71375","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.71375","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.71375","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:03:26Z","timestamp":1790564606000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/10.1111\/dom.71375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":40,"alternative-id":["10.1111\/dom.71375"],"URL":"https:\/\/doi.org\/10.1111\/dom.71375","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]},"assertion":[{"value":"2026-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"dom.71375"}}