{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:00:19Z","timestamp":1787313619320,"version":"build-2736575974"},"reference-count":40,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Intern Med"],"published-print":{"date-parts":[[2023,7,1]]},"abstract":"\n Importance<\/jats:title>\n Type 2 diabetes (T2D) is the leading cause of kidney disease in the US. It is not known whether glucose-lowering medications differentially affect kidney function.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate kidney outcomes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) trial comparing 4 classes of glucose-lowering medications added to metformin for glycemic management in individuals with T2D.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n A randomized clinical trial was conducted at 36 sites across the US. Participants included adults with T2D for less than 10 years, a hemoglobin A\n 1c<\/jats:sub>\n level between 6.8% and 8.5%, and estimated glomerular filtration rate (eGFR) greater than or equal to 60 mL\/min\/1.73 m\n 2<\/jats:sup>\n who were receiving metformin treatment. A total of 5047 participants were enrolled between July 8, 2013, and August 11, 2017, and followed up for a mean of 5.0 years (range, 0-7.6 years). Data were analyzed from February 21, 2022, to March 27, 2023.\n <\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n \n Addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin, with the medication combination continued until the HbA\n 1c<\/jats:sub>\n was greater than 7.5%; thereafter, insulin was added to maintain glycemic control.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n Chronic eGFR slope (change in eGFR between year 1 and trial end) and a composite kidney disease progression outcome (albuminuria, dialysis, transplant, or death due to kidney disease). Secondary outcomes included incident eGFR less than 60 mL\/min\/1.73 m\n 2<\/jats:sup>\n , 40% decrease in eGFR to less than 60 mL\/min\/1.73 m\n 2<\/jats:sup>\n , doubling of urine albumin-to-creatinine ratio (UACR) to 30 mg\/g or greater, and progression of Kidney Disease Improving Global Outcomes stage. Analyses were intention-to-treat.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of the 5047 participants, 3210 (63.6%) were men. Baseline characteristics were mean (SD) age 57.2 (10.0) years; HbA\n 1c<\/jats:sub>\n 7.5% (0.5%); diabetes duration, 4.2 (2.7) years; body mass index, 34.3 (6.8); blood pressure 128.3\/77.3 (14.7\/9.9) mm Hg; eGFR 94.9 (16.8) mL\/min\/1.73 m\n 2<\/jats:sup>\n ; and median UACR, 6.4 (IQR 3.1-16.9) mg\/g; 2933 (58.1%) were treated with renin-angiotensin-aldosterone inhibitors. Mean chronic eGFR slope was \u22122.03 (95% CI, \u22122.20 to \u22121.86) mL\/min\/1.73 m\n 2<\/jats:sup>\n per year for patients receiving sitagliptin; glimepiride, \u22121.92 (95% CI, \u22122.08 to \u22121.75) mL\/min\/1.73 m\n 2<\/jats:sup>\n per year; liraglutide, \u22122.08 (95% CI, \u22122.26 to \u22121.90) mL\/min\/1.73 m\n 2<\/jats:sup>\n per year; and insulin glargine, \u22122.02 (95% CI, \u22122.19 to \u22121.84) mL\/min\/1.73 m\n 2<\/jats:sup>\n per year (\n P<\/jats:italic>\n \u2009=\u2009.61). Mean composite kidney disease progression occurred in 135 (10.6%) patients receiving sitagliptin; glimepiride, 155 (12.4%); liraglutide, 152 (12.0%); and insulin glargine, 150 (11.9%) (\n P<\/jats:italic>\n \u2009=\u2009.56). Most of the composite outcome was attributable to albuminuria progression (98.4%). There were no significant differences by treatment assignment in secondary outcomes. There were no adverse kidney events attributable to medication assignment.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this randomized clinical trial, among people with T2D and predominantly free of kidney disease at baseline, no significant differences in kidney outcomes were observed during 5 years of follow-up when a dipeptidyl peptidase 4 inhibitor, sulfonylurea, glucagonlike peptide 1 receptor agonist, or basal insulin was added to metformin for glycemic control.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT01794143<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamainternmed.2023.1487","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T11:33:54Z","timestamp":1684755234000},"page":"705","source":"Crossref","is-referenced-by-count":38,"title":["Comparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Type 2 Diabetes"],"prefix":"10.1001","volume":"183","author":[{"given":"Deborah J.","family":"Wexler","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital Diabetes Center and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian H.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Kidney Research Institute, University of Washington, Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alokananda","family":"Ghosh","sequence":"additional","affiliation":[{"name":"George Washington University Biostatistics Center, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naji","family":"Younes","sequence":"additional","affiliation":[{"name":"George Washington University Biostatistics Center, Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ionut","family":"Bebu","sequence":"additional","affiliation":[{"name":"George 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