PMID- 32444457 OWN - NLM STAT- MEDLINE DCOM- 20210219 LR - 20210219 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 43 IP - 8 DP - 2020 Aug TI - Effects of Linagliptin on Cardiovascular and Kidney Outcomes in People With Normal and Reduced Kidney Function: Secondary Analysis of the CARMELINA Randomized Trial. PG - 1803-1812 LID - 10.2337/dc20-0279 [doi] AB - OBJECTIVE: Type 2 diabetes is a leading cause of kidney failure, but few outcome trials proactively enrolled individuals with chronic kidney disease (CKD). We performed secondary analyses of cardiovascular (CV) and kidney outcomes across baseline estimated glomerular filtration rate (eGFR) categories (>/=60, 45 to <60, 30 to <45, and <30 mL/min/1.73 m(2)) in Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA), a cardiorenal placebo-controlled outcome trial of the dipeptidyl peptidase 4 inhibitor linagliptin (NCT01897532). RESEARCH DESIGN AND METHODS: Participants with CV disease and/or CKD were included. The primary outcome was time to first occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke (three-point major adverse CV event [3P-MACE]), with a secondary outcome of renal death, end-stage kidney disease, or sustained >/=40% decrease in eGFR from baseline. Other end points included progression of albuminuria, change in HbA(1c), and adverse events (AEs) including hypoglycemia. RESULTS: A total of 6,979 subjects (mean age 65.9 years; eGFR 54.6 mL/min/1.73 m(2); 80.1% albuminuria) were followed for 2.2 years. Across eGFR categories, linagliptin as compared with placebo did not affect the risk for 3P-MACE (hazard ratio 1.02 [95% CI 0.89, 1.17]) or the secondary kidney outcome (1.04 [0.89, 1.22]) (interaction P values >0.05). Regardless of eGFR, albuminuria progression was reduced with linagliptin, as was HbA(1c), without increasing risk for hypoglycemia. AEs were balanced among groups overall and across eGFR categories. CONCLUSIONS: Across all GFR categories, in participants with type 2 diabetes and CKD and/or CV disease, there was no difference in risk for linagliptin versus placebo on CV and kidney events. Significant reductions in risk for albuminuria progression and HbA(1c) and no difference in AEs were observed. CI - (c) 2020 by the American Diabetes Association. FAU - Perkovic, Vlado AU - Perkovic V AUID- ORCID: 0000-0002-4257-7620 AD - Faculty of Medicine, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia vlado.perkovic@unsw.edu.au. FAU - Toto, Robert AU - Toto R AD - University of Texas Southwestern Medical Center, Dallas, TX. FAU - Cooper, Mark E AU - Cooper ME AD - Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia. FAU - Mann, Johannes F E AU - Mann JFE AD - Kuratorium fur Dialyse Kidney Centre, Munich, Germany. AD - Department of Nephrology, Friedrich-Alexander University of Erlangen-Nurnberg, Erlangen, Germany. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Dallas Diabetes Research Center, Dallas, TX. FAU - McGuire, Darren K AU - McGuire DK AUID- ORCID: 0000-0002-6412-7989 AD - University of Texas Southwestern Medical Center, Dallas, TX. FAU - Kahn, Steven E AU - Kahn SE AD - Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA. FAU - Marx, Nikolaus AU - Marx N AUID- ORCID: 0000-0001-6141-634X AD - Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Aachen, Germany. FAU - Alexander, John H AU - Alexander JH AD - Duke Clinical Research Institute, Duke Health, Durham, NC. FAU - Zinman, Bernard AU - Zinman B AUID- ORCID: 0000-0002-0041-1876 AD - Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. AD - Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada. FAU - Pfarr, Egon AU - Pfarr E AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. FAU - Schnaidt, Sven AU - Schnaidt S AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Meinicke, Thomas AU - Meinicke T AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - von Eynatten, Maximillian AU - von Eynatten M AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. FAU - George, Jyothis T AU - George JT AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. FAU - Johansen, Odd Erik AU - Johansen OE AUID- ORCID: 0000-0003-2470-0530 AD - Boehringer Ingelheim Norway KS, Asker, Norway. FAU - Wanner, Christoph AU - Wanner C AUID- ORCID: 0000-0001-9507-5301 CN - CARMELINA investigators LA - eng SI - ClinicalTrials.gov/NCT01897532 SI - figshare/10.2337/figshare.12129993 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200522 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 3X29ZEJ4R2 (Linagliptin) SB - IM MH - Aged MH - Cardiovascular Diseases/*epidemiology/etiology/prevention & control MH - Cardiovascular System/*drug effects MH - Diabetes Mellitus, Type 2/complications/diagnosis/*drug therapy/epidemiology MH - Diabetic Nephropathies/drug therapy/epidemiology MH - Dipeptidyl-Peptidase IV Inhibitors/pharmacology/therapeutic use MH - Female MH - Glomerular Filtration Rate/drug effects MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Incidence MH - Kidney/*drug effects MH - Kidney Failure, Chronic/complications/*epidemiology/physiopathology/prevention & control MH - Linagliptin/*pharmacology/therapeutic use MH - Male MH - Middle Aged MH - Mortality MH - Prognosis MH - Renal Insufficiency, Chronic/complications/drug therapy/epidemiology/physiopathology MH - Retrospective Studies MH - Treatment Outcome PMC - PMC7372065 EDAT- 2020/05/24 06:00 MHDA- 2021/02/20 06:00 PMCR- 2020/05/22 CRDT- 2020/05/24 06:00 PHST- 2020/02/09 00:00 [received] PHST- 2020/04/06 00:00 [accepted] PHST- 2020/05/24 06:00 [pubmed] PHST- 2021/02/20 06:00 [medline] PHST- 2020/05/24 06:00 [entrez] PHST- 2020/05/22 00:00 [pmc-release] AID - dc20-0279 [pii] AID - 200279 [pii] AID - 10.2337/dc20-0279 [doi] PST - ppublish SO - Diabetes Care. 2020 Aug;43(8):1803-1812. doi: 10.2337/dc20-0279. Epub 2020 May 22.