Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials.

Autor:	Badve SV; St George Hospital, Sydney, NSW, Australia; Renal and Metabolic Division, The George Institute for Global Health, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia. Electronic address: sbadve@georgeinstitute.org.au., Bilal A; AdventHealth Translational Research Institute, Orlando, FL, USA., Lee MMY; School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK., Sattar N; School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK., Gerstein HC; Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada., Ruff CT; TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., McMurray JJV; School of Cardiovascular and Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK., Rossing P; Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Bakris G; American Society of Hypertension Comprehensive Hypertension Center, University of Chicago Medicine and Biological Sciences, Chicago, IL, USA., Mahaffey KW; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA, USA., Mann JFE; KfH Kidney Center, Munich, Germany; University Hospital, Friedrich-Alexander University, Erlangen, Germany., Colhoun HM; Institute of Genetics and Molecular Medicine, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK., Tuttle KR; University of Washington School of Medicine, Seattle, WA, USA; Providence Inland Northwest Health, Spokane, WA, USA., Pratley RE; AdventHealth Translational Research Institute, Orlando, FL, USA., Perkovic V; Renal and Metabolic Division, The George Institute for Global Health, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia.
Jazyk:	angličtina
Zdroj:	The lancet. Diabetes & endocrinology [Lancet Diabetes Endocrinol] 2025 Jan; Vol. 13 (1), pp. 15-28. Date of Electronic Publication: 2024 Nov 25.
DOI:	10.1016/S2213-8587(24)00271-7
Abstrakt:	Background: GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACE) and can also have kidney benefits. However, whether GLP-1 receptor agonists improve clinically important kidney outcomes remains uncertain. We aimed to comprehensively assess the effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes by performing a meta-analysis of randomised controlled trials. Methods: For this meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials that included at least 500 participants with type 2 diabetes, compared a GLP-1 receptor agonist with placebo with at least 12 months of follow-up, and reported a primary clinical kidney or cardiovascular outcome, from database inception to March 26, 2024. Post hoc, we included the SELECT trial (NCT03574597), which enrolled participants with cardiovascular disease and a BMI of 27 kg/m 2 or more without diabetes. Study-level summary data were extracted independently by two authors for inclusion in this random-effects analysis. The main kidney outcome was a composite outcome, consisting of kidney failure (kidney replacement therapy or a persistent estimated glomerular filtration rate [eGFR] <15 mL/min per 1·73 m 2 ), a sustained reduction in eGFR by at least 50% or the nearest equivalent, or death from kidney failure. The main cardiovascular outcome was MACE, consisting of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. This study is registered with PROSPERO, CRD42024528864. Findings: Of the 5140 records identified through the literature search, 11 trials, involving 85 373 participants (29 386 female, 55 987 male), were included in the meta-analysis. In participants with type 2 diabetes (67 769), GLP-1 receptor agonists reduced the composite kidney outcome by 18% compared with placebo (hazard ratio [HR] 0·82, 95% CI 0·73-0·93; I 2 =26·41%), kidney failure by 16% (HR 0·84, 0·72-0·99; I 2 =0%), MACE by 13% (HR 0·87, 0·81-0·93; I 2 =49·75%), and all-cause death by 12% (HR 0·88, 0·83-0·93; I 2 =0%). The effect on the composite kidney outcome (HR 0·81, 95% CI 0·72-0·92; I 2 =23·11%), kidney failure (HR 0·84, 0·72-0·98; I 2 =0%), MACE (HR 0·86, 0·80-0·92; I 2 =48·9%), and all-cause death (HR 0·87, 0·82-0·91; I 2 =0%) was similar when the SELECT trial was included, with no evidence of heterogeneity between this trial and those including participants with type 2 diabetes (p heterogeneity >0·05). There was no difference in the risk of serious adverse events, including acute pancreatitis and severe hypoglycaemia, between the GLP-1 receptor agonist and placebo groups (risk ratio [RR] 0·95, 95% CI 0·90-1·01; I 2 =88·5%). However, treatment discontinuation due to adverse events occurred more frequently in the GLP-1 receptor agonist groups (RR 1·51, 95% CI 1·18-1·94; I 2 =96·3%). Interpretation: We found evidence that GLP-1 receptor agonists significantly reduce clinically important kidney events, kidney failure, and cardiovascular events. Funding: None. Competing Interests: Declaration of interests SVB reports consulting fees from Bayer, AstraZeneca, GSK, and Vifor Pharma; speaking fees from Bayer, AstraZeneca, Pfizer, and Vifor Pharma (all honoraria paid to his institution); and non-financial research support from Bayer. MMYL reports receiving grants through his employer, the University of Glasgow, from AstraZeneca, Boehringer Ingelheim, and Roche Diagnostics; MMYL is a member of a trial steering committee for Cytokinetics and a clinical endpoints committee for Bayer. NS reports consulting and speaking fees from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, Sanofi, and ZP Therapeutics; and grants from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics, paid to the University of Glasgow. HCG holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly, AstraZeneca, Novo Nordisk, Hanmi, and Merck; continuing education grants from Eli Lilly, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly, Novo Nordisk, DKSH, Zuellig, Sanofi, Carbon Brand, and Jiangsu Hanson; and consulting fees from Abbott, Bayer, Eli Lilly, Novo Nordisk, Pfizer, Sanofi, Kowa, and Hanmi. CTR reports research grants through Brigham and Women's Hospital from Anthos, AstraZeneca, Daiichi Sankyo, Janssen, and Novartis; and has received honoraria for scientific advisory boards and consulting from Anthos, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Janssen, and Pfizer. JJVM reports payments to his employer, the University of Glasgow, for work on clinical trials, consulting, lecturing, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Cytokinetics, Dal-Cor, GSK, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos; personal lecture fees from Abbott, Hikma, Sun Pharmaceuticals, Servier, and Theracos; and personal payments from Abbott, Hikma, Ionis, Sun Pharmaceuticals, and Servier. PR has received grants to his institution from Novo Nordisk, AstraZeneca, and Bayer; and has received honoraria for scientific advisory boards and steering groups from AstraZeneca, Abbott, Bayer, Boehringer Ingelheim, Gilead, Novo Nordisk, Sanofi, Eli Lilly, and Novartis. GB has received honoraria from Bayer, KBP Biosciences, Alnylam, AstraZeneca, Novo Nordisk, and InREGEN. KWM has received grants from AHA, Apple, Bayer, California Institute Regenerative Medicine (CIRM), CSL Behring, Eidos, Ferring, Gilead, Google (Verify), Idorsia, Johnson & Johnson, Luitpold, Novartis, PAC-12, Precordior, and Sanifit; and consulting fees from Applied Therapeutics, Bayer, BMS, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson & Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, Phasebio, Portola, Quidel, and Theravance; and has equity in Human, Medeloop, Precordior, and Regencor. JFEM reports grants from Novo Nordisk, the EU, and McMaster University (Hamilton, Canada); consulting fees from Novo Nordisk, AstraZeneca, Bayer, and Boehringer Ingelheim; honoraria from Novo Nordisk, AstraZeneca, Bayer, and Novartis; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi, and Boehringer Ingelheim, and has had a leadership role in the Kidney Disease Improving Global Outcomes group. HMC reports serving on advisory panels for Novo Nordisk and Bayer; receiving research funding from Sanofi, Roche, and IQVIA; receiving grants from the Chief Scientist Office, Diabetes UK, the European Commission, JDRF (Breakthrough T1D), and the Medical Research Council; serving on a speaker's bureau for Novo Nordisk; and holding stock in Roche and Bayer. KRT is supported by National Institutes of Health research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, OT2OD032581 and Centers for Disease Control and Prevention project numbers 75D301–21-P-12254 and 75D301–23-C-18264. She has also received investigator-initiated grant support from Travere Therapeutics, Bayer, and the Doris Duke Charitable Foundation, outside of the submitted work. She reports consultancy fees from AstraZeneca, Boehringer Ingelheim, Bayer, Eli Lilly, Novo Nordisk, Travere Therapeutics, and Pfizer; and speaker fees from Novo Nordisk. REP reports speaker fees from Eli Lilly and Novo Nordisk; consulting fees from Bayer, Bayer HealthCare Pharmaceuticals, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Intas Pharmaceuticals, Eli Lilly, Novo Nordisk, Pfizer, and Sun Pharmaceutical Industries; and grants from Biomea Fusion, Carmot Therapeutics, Dompé, Endogenex, Fractyl, Eli Lilly, Novo Nordisk, and Sanofi. VP has received honoraria for roles on steering committees, data monitoring committees, or advisory boards or for scientific presentations from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, GSK, Janssen, Novo Nordisk, Novartis, Otsuka, Travere, Tricida, and UpToDate; and is Board Director for George Clinical, St Vincents Health Australia and several independent medical research institutes. AB declares no competing interests. (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
Databáze:	MEDLINE
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