Glucagon-like peptide-1 receptor agonists and kidney outcomes.
Humans
Glucagon-Like Peptide-1 Receptor
/ agonists
Diabetes Mellitus, Type 2
/ drug therapy
Renal Insufficiency, Chronic
/ drug therapy
Diabetic Nephropathies
/ drug therapy
Hypoglycemic Agents
/ therapeutic use
Glucagon-Like Peptides
/ therapeutic use
Glomerular Filtration Rate
/ drug effects
Kidney
/ drug effects
Disease Progression
Glucagon-Like Peptide-1 Receptor Agonists
albuminuria
cardiovascular outcome trials
diabetes
diabetic nephropathy
eGFR
glucagon‐like peptide‐1 receptor agonists
kidney
Journal
Journal of diabetes
ISSN: 1753-0407
Titre abrégé: J Diabetes
Pays: Australia
ID NLM: 101504326
Informations de publication
Date de publication:
Oct 2024
Oct 2024
Historique:
revised:
06
06
2024
received:
25
03
2024
accepted:
18
07
2024
medline:
4
10
2024
pubmed:
4
10
2024
entrez:
4
10
2024
Statut:
ppublish
Résumé
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained increasing attention for their potential benefits in people with type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD). Most supportive evidence of a kidney-protective effect of the GLP-1RA class of medications has been derived from kidney-related outcomes reported from cardiovascular outcome trials (CVOTs). GLP-1RAs have been shown to reduce albuminuria, mitigate cardiovascular risk, and possibly attenuate estimated glomerular filtration rate (eGFR) decline. The kidney-protective effects of GLP-1RAs are thought to be attributed to their anti-inflammatory, antioxidant, and vasodilatory properties. Despite these promising findings, the use of GLP-RAs has yet to be definitively shown to slow progression to chronic kidney failure in people with T2DM. The Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease (FLOW trial) is the first major trial assessing the potential of a GLP-1RA to slow progression of kidney disease in people with established CKD to clinically important kidney end points. On March 5, 2024, the top line result from FLOW was announced with semaglutide 1.0 mg being reported to reduce the primary end point of the trial by a significant 24% compared with placebo. Here, we summarize the kidney outcomes reported from CVOTs for the GLP-1RA class of medication and briefly describe kidney outcomes from other major GLP-1RAs trials. We also discuss a potential role of the dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, tirzepatide, as a kidney-protective agent.
Identifiants
pubmed: 39364792
doi: 10.1111/1753-0407.13609
doi:
Substances chimiques
Glucagon-Like Peptide-1 Receptor
0
Hypoglycemic Agents
0
Glucagon-Like Peptides
62340-29-8
semaglutide
53AXN4NNHX
Glucagon-Like Peptide-1 Receptor Agonists
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13609Subventions
Organisme : Novo Nordisk
Organisme : Servier
Organisme : Medtronic
Organisme : The Rebecca Cooper Medical Research Foundation
Organisme : St Vincent's Research Foundation
Organisme : The Juvenile Diabetes Research Foundation (T1D)
Organisme : Gray Innovations
Organisme : The Diabetes Australia Research Trust/Program
Organisme : The National Health and Medical Research Council of Australia
Organisme : Eli Lilly
Organisme : Sanofi Aventis
Organisme : Astra Zeneca
Organisme : Merck Sharp & Dohme
Organisme : Norvartis
Organisme : Boehringer Ingelheim
Organisme : Amgen
Organisme : Versanis
Organisme : Endogenex
Organisme : The University of Melbourne
Informations de copyright
© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.
Références
US Food and Drug Administration. Guidance for industry diabetes mellitus‐evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. 2008 https://www.fda.gov/media/71297/download
Rajan T, Ferro EG, Elshazly MB. 2020 FDA guidance for diabetes drug development: cardiorenal populations and outcomes: lessons learned and future directions. 2021 September 11, 2021. Accessed March 9, 2024. https://www.acc.org/Latest-in-Cardiology/Articles/2021/09/10/13/46/2020-FDA-Guidance-for-Diabetes-Drug-Development
Sattar N, Lee MMY, Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP‐1 receptor agonists in patients with type 2 diabetes: a systematic review and meta‐analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9(10):653‐662. doi:10.1016/S2213‐8587(21)00203‐5
Naaman SC, Bakris GL. Diabetic nephropathy: update on pillars of therapy slowing progression. Diabetes Care. 2023;46(9):1574‐1586. doi:10.2337/dci23‐0030
Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247‐2257. doi:10.1056/NEJMoa1509225
Marso SP, Daniels GH, Brown‐Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311‐322. doi:10.1056/NEJMoa1603827
Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834‐1844. doi:10.1056/NEJMoa1607141
Holman RR, Bethel MA, Mentz RJ, et al. Effects of once‐weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377(13):1228‐1239. doi:10.1056/NEJMoa1612917
Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double‐blind, randomised placebo‐controlled trial. Lancet. 2018;392(10157):1519‐1529. doi:10.1016/j.ahj.2018.03.030
Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double‐blind, randomised placebo‐controlled trial. Lancet. 2019;394(10193):121‐130. doi:10.1016/S0140‐6736(19)31149‐3
Husain M, Birkenfeld AL, Donsmark M, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381(9):841‐851. doi:10.1056/NEJMoa1901118
Gerstein HC, Sattar N, Rosenstock J, et al. Cardiovascular and renal outcomes with Efpeglenatide in type 2 diabetes. N Engl J Med. 2021;385(10):896‐907. doi:10.1056/NEJMoa2108269
Kristensen SL, Rørth R, Jhund PS, et al. Cardiovascular, mortality, and kidney outcomes with GLP‐1 receptor agonists in patients with type 2 diabetes: a systematic review and meta‐analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019;7(10):776‐785. doi:10.1016/S2213‐8587(19)30249‐9
MacIsaac RJ, Thomas MC. Effects of diabetes medications targeting the Incretin system on the kidney. Clin J Am Soc Nephrol. 2018;13(2):321‐323. doi:10.2215/cjn.10380917
Sourris KC, Ding Y, Maxwell SS, et al. Glucagon‐like peptide‐1 receptor signaling modifies the extent of diabetic kidney disease through dampening the receptor for advanced glycation end products–induced inflammation. Kidney Int. 2024;105(1):132‐149. doi:10.1016/j.kint.2023.09.029
Muskiet MHA, Tonneijck L, Smits MM, et al. GLP‐1 and the kidney: from physiology to pharmacology and outcomes in diabetes. Nat Rev Nephrol. 2017;13(10):605‐628. doi:10.1038/nrneph.2017.123
MacIsaac RJ, Jerums G, Ekinci EI. Glycemic control as primary prevention for diabetic kidney disease. Adv Chronic Kidney Dis. 2018;25(2):141‐148. doi:10.1053/j.ackd.2017.11.003
Rossing P, Baeres FMM, Bakris G, et al. The rationale, design and baseline data of FLOW, a kidney outcomes trial with once‐weekly semaglutide in people with type 2 diabetes and chronic kidney disease. Nephrol Dial Transplant. 2023;38(9):2041‐2051. doi:10.1093/ndt/gfad009
Novo Nordisk will stop the once‐weekly injectable semaglutide kidney outcomes trial, FLOW, based on interim analysis. 2023 October 11, 2023. Accessed October 25, 2023. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=166327
Novo Nordisk. Semaglutide 1.0 mg demonstrates 24% reduction in the risk of kidney disease‐related events in people with type 2 diabetes and chronic kidney disease in the FLOW trial. 2024 March 5, 2024. Accessed March 9, 2024. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=167028
Lincoff AM, Brown‐Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221‐2232. doi:10.1056/NEJMoa2307563
Hinton W, Feher M, Munro N, Walker M, de Lusignan S. Real‐world prevalence of the inclusion criteria for the LEADER trial: data from a national general practice network. Diabetes Obes Metab. 2019;21(7):1661‐1667. doi:10.1111/dom.13710
Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43(6):474‐484. doi:10.1093/eurheartj/ehab777
Caruso I, Cignarelli A, Sorice GP, et al. Cardiovascular and renal effectiveness of GLP‐1 receptor agonists vs. other glucose‐lowering drugs in type 2 diabetes: a systematic review and meta‐analysis of real‐world studies. Metabolites. 2022;12(2):183. doi:10.3390/metabo12020183
Mann JFE, Ørsted DD, Brown‐Frandsen K, et al. Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med. 2017;377(9):839‐848. doi:10.1056/NEJMoa1616011
Botros FT, Gerstein HC, Malik R, et al. Dulaglutide and kidney function–related outcomes in type 2 diabetes: a REWIND post hoc analysis. Diabetes Care. 2023;46(8):1524‐1530. doi:10.2337/dc23‐0231
Gerstein HC, Mian R, Ramasundarahettige C, et al. Cardiovascular and renal outcomes with varying degrees of kidney disease in high‐risk people with type 2 diabetes: an epidemiological analysis of data from the AMPLITUDE‐O trial. Diabetes Obes Metab. 2024;26:1216‐1223. doi:10.1111/dom.15417
Bethel MA, Mentz RJ, Merrill P, et al. Microvascular and cardiovascular outcomes according to renal function in patients treated with once‐weekly Exenatide: insights from the EXSCEL trial. Diabetes Care. 2019;43(2):446‐452. doi:10.2337/dc19‐1065
Idzerda NMA, Clegg LE, Hernandez AF, et al. Prediction and validation of exenatide risk marker effects on progression of renal disease: insights from EXSCEL. Diabetes Obes Metab. 2020;22(5):798‐806. doi:10.1111/dom.13958
Tuttle KR, Bosch‐Traberg H, Cherney DZI, et al. Post hoc analysis of SUSTAIN 6 and PIONEER 6 trials suggests that people with type 2 diabetes at high cardiovascular risk treated with semaglutide experience more stable kidney function compared with placebo. Kidney Int. 2023;103(4):772‐781. doi:10.1016/j.kint.2022.12.028
Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo‐controlled trial. Lancet. 2019;394(10193):131‐138. doi:10.1016/S0140‐6736(19)31150‐X
Muskiet Marcel HAM. Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo‐controlled trial. Lancet Diabetes Endocrinol. 2018;6(11):859‐869.
Shaman AM, Bain SC, Bakris GL, et al. Effect of the glucagon‐like peptide‐1 receptor agonists semaglutide and liraglutide on kidney outcomes in patients with type 2 diabetes: pooled analysis of SUSTAIN 6 and LEADER. Circulation. 2022;145(8):575‐585. doi:10.1161/circulationaha.121.055459
van der Aart‐van der Beek AB, Clegg LE, Penland RC, et al. Effect of once‐weekly exenatide on estimated glomerular filtration rate slope depends on baseline renal risk: a post hoc analysis of the EXSCEL trial. Diabetes Obes Metab. 2020;22(12):2493‐2498. doi:10.1111/dom.14175
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295‐2306. doi:10.1056/NEJMoa1811744
Tuttle Katherine RK. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate‐to‐severe chronic kidney disease (AWARD‐7): a multicentre, open‐label, randomised trial. Lancet Diabetes Endocrinol. 2018;6(8):605‐617.
Tuttle KR, Rayner B, Lakshmanan MC, et al. Clinical outcomes by albuminuria status with Dulaglutide versus insulin glargine in participants with diabetes and CKD: AWARD‐7 exploratory analysis. Kidney360. 2021;2(2):254‐262. doi:10.34067/kid.0005852020
Schechter M, Melzer Cohen C, Fishkin A, et al. Kidney function loss and albuminuria progression with GLP‐1 receptor agonists versus basal insulin in patients with type 2 diabetes: real‐world evidence. Cardiovasc Diabetol. 2023;22(1):126. doi:10.1186/s12933‐023‐01829‐0
Peng ZY, Yang CT, Lin WH, Yao WY, Ou HT, Kuo S. Chronic kidney outcomes associated with GLP‐1 receptor agonists versus long‐acting insulins among type 2 diabetes patients requiring intensive glycemic control: a nationwide cohort study. Cardiovasc Diabetol. 2023;22(1):272. doi:10.1186/s12933‐023‐01991‐5
MacIsaac RJ, Deed G, D'Emden M, et al. Challenging clinical perspectives in type 2 diabetes with Tirzepatide, a first‐in‐class Twincretin. Diabetes Ther. 2023;14(12):1997‐2014. doi:10.1007/s13300‐023‐01475‐5
Karakasis P, Patoulias D, Fragakis N, Klisic A, Rizzo M. Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: a systematic review and multilevel meta‐analysis. Diabetes Obes Metab. 2024;26(3):1090‐1104. doi:10.1111/dom.15410
Heerspink HJL, Sattar N, Pavo I, et al. Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS‐4 trial: post‐hoc analysis of an open‐label, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022;10(11):774‐785. doi:10.1016/S2213‐8587(22)00243‐1
Heerspink HJL, Sattar N, Pavo I, et al. Effects of Tirzepatide versus insulin glargine on cystatin C–based kidney function: a SURPASS‐4 post hoc analysis. Diabetes Care. 2023;46(8):1501‐1506. doi:10.2337/dc23‐0261
Bjornstad P, Cherney D, Lawson J, et al. MO399: Remodel: a mechanistic trial evaluating the effects of Semaglutide on the kidneys in people with type 2 diabetes and chronic kidney disease. Nephrol Dial Transplant. 2022;37(Supplement_3):gfac070.013. doi:10.1093/ndt/gfac070.013
Rossing P, Caramori ML, Chan JCN, et al. Executive summary of the KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease: an update based on rapidly emerging new evidence. Kidney Int. 2022;102(5):990‐999. doi:10.1016/j.kint.2022.06.013
Committee ADAPP. 9. Pharmacologic approaches to glycemic treatment: standards of care in diabetes—2024. Diabetes Care. 2023;47(Supplement_1):S158‐S178. doi:10.2337/dc24‐S009
Lam CSP, Ramasundarahettige C, Branch KRH, et al. Efpeglenatide and clinical outcomes with and without concomitant sodium‐glucose cotransporter‐2 inhibition use in type 2 diabetes: exploratory analysis of the AMPLITUDE‐O trial. Circulation. 2022;145(8):565‐574. doi:10.1161/CIRCULATIONAHA.121.057934
Sivalingam S, Wasehuus VS, Rotbain Curovic V, et al. Albuminuria‐lowering effect of adding semaglutide on top of empagliflozin in individuals with type 2 diabetes: a randomized and placebo‐controlled study. Diabetes Obes Metab. 2024;26(1):54‐64. doi:10.1111/dom.15287
Simms‐Williams N, Treves N, Yin H, et al. Effect of combination treatment with glucagon‐like peptide‐1 receptor agonists and sodium‐glucose cotransporter‐2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study. BMJ. 2024;385:e078242. doi:10.1136/bmj‐2023‐078242
Neuen BL, Heerspink HJL, Vart P, et al. Estimated lifetime cardiovascular, kidney, and mortality benefits of combination treatment with SGLT2 inhibitors, GLP‐1 receptor agonists, and nonsteroidal MRA compared with conventional Care in Patients with Type 2 diabetes and albuminuria. Circulation. 2024;149(6):450‐462. doi:10.1161/CIRCULATIONAHA.123.067584
Khurana N, James S, Coughlan MT, MacIsaac RJ, Ekinci EI. Novel therapies for kidney disease in people with diabetes. J Clin Endocrinol Metab. 2022;107(1):e1‐e24. doi:10.1210/clinem/dgab639
Cardoso P, Young KG, Nair ATN, et al. Phenotype‐based targeted treatment of SGLT2 inhibitors and GLP‐1 receptor agonists in type 2 diabetes. Diabetologia. 2024;67(5):822‐836. doi:10.1007/s00125‐024‐06099‐3
Trial of Semaglutide for Diabetic Kidney Disease in Type 1 Diabetes (RT1D). Clinicaltrials.Gov identifier: NCT05822609. Accessed April 21, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05822609