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Liraglutide and Renal Outcomes in Type 2 Diabetes
Open accessAbstract
BACKGROUND: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown. METHODS: We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed. RESULTS: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively). CONCLUSIONS: This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).
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“The LEADER and REWIND trials also report a greater than 20% reduction in the risk of developing new macroalbuminuria, along with favourable trends in other clinically relevant adverse renal outcomes. 26,27”
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“Glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) have also been shown to improve kidney outcomes (95-100).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [97]
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“GLP-1 RAs have also been shown to improve kidney outcomes (104-109).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [106]
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“However, the composite kidney outcomes in these trials were evaluated as secondary outcomes, and the reported effects were largely driven by a lower risk of new-onset macroalbuminuria. 23-25”
From Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials (2025) · cites this paper as [24]
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“Treatment with these drugs is in fact associated with a reduced decline in the estimated glomerular filtration rate (eGFR), as well as with a reduction in urinary albumin excretion and in the incidence rate of de novo albuminuria [28,29].”
From GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives (2023) · cites this paper as [28]
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“However, these benefits were driven by a lower risk of persistent macroalbuminuria [6,10,13].”
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Citations
Cites
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504720 · Cited by 12,315
Self-citationEffects of Intensive Glucose Lowering in Type 2 Diabetes
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802743 · Cited by 7,888
10-year follow-up of intensive glucose control in type 2 diabetes
Holman, R. R., Paul, S. K., Bethel, M. A., Matthews, D. R., & Neil, H. A. W. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0806470 · Cited by 7,751
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, N. R., Ravn, L. S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603827 · Cited by 7,629
Self-citationEmpagliflozin and Progression of Kidney Disease in Type 2 Diabetes
Wanner, C., Inzucchi, S. E., Lachin, J. M., Fitchett, D., von Eynatten, M., Mattheus, M., Johansen, O. E., Woerle, H. J., Broedl, U. C., & Zinman, B. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1515920 · Cited by 3,655
Self-citationStevens, P. E., Levin, A., & for the Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members* (2013) · Annals of Internal Medicine · doi:10.7326/0003-4819-158-11-201306040-00007 · Cited by 3,607
Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus
Scirica, B. M., Bhatt, D. L., Braunwald, E., Steg, P. G., Davidson, J., Hirshberg, B., Ohman, P., Frederich, R., Wiviott, S. D., Hoffman, E. B., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1307684 · Cited by 3,470
Assessing Kidney Function — Measured and Estimated Glomerular Filtration Rate
Stevens, L. A., Coresh, J., Greene, T., & Levey, A. S. (2006) · New England Journal of Medicine · doi:10.1056/nejmra054415 · Cited by 2,952
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Cosentino, F., Grant, P. J., Aboyans, V., Bailey, C. J., Ceriello, A., Delgado, V., Federici, M., Filippatos, G., Grobbee, D. E., Hansen, T. B., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz486 · Cited by 4,763
Davies, M. J., D’Alessio, D. A., Fradkin, J., Kernan, W. N., Mathieu, C., Mingrone, G., Rossing, P., Tsapas, A., Wexler, D. J., & Buse, J. B. (2018) · Diabetes Care · doi:10.2337/dci18-0033 · Cited by 3,518
Self-citationKristensen, S. L., Rørth, R., Jhund, P. S., Docherty, K. F., Sattar, N., Preiss, D., Køber, L., Petrie, M. C., & McMurray, J. J. V. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30249-9 · Cited by 1,663
GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art
Nauck, M. A., Quast, D. R., Wefers, J., & Meier, J. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101102 · Cited by 1,647
“The discovery of beneficial renal effects using GLP-1 RAs is a recent achievement mainly based on the observations that GLP-1 RAs prevented new-onset macroalbuminuria [99,164,165], reduced urinary albumin excretion [164,165], or slowed the decline in the estimated glomerular filtration rate (eGFR) over time [164e166].”
BackgroundSattar, N., Lee, M. M. Y., Kristensen, S. L., Branch, K. R. H., Del Prato, S., Khurmi, N. S., Lam, C. S. P., Lopes, R. D., McMurray, J. J. V., Pratley, R. E., et al. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00203-5 · Cited by 1,599
Metadata
- Authors
- Mann, J. F. E., Ørsted, D. D., Brown-Frandsen, K., Marso, S. P., Poulter, N. R., Rasmussen, S., Tornøe, K., Zinman, B., & Buse, J. B.
- Affiliations
- Mount Sinai Hospital (CA)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-08-31
- Volume
- 377
- Issue
- 9
- Pages
- 839-848
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2752707491
- Semantic Scholar
- e3932087f500b455476965939bdced15360eb028
- Cited by
- 1,253
- References
- 32
- Citations by year
- 2026: 99 · 2025: 116 · 2024: 121 · 2023: 131 · 2022: 134 · 2021: 161 · 2020: 180 · 2019: 139 · 2018: 152 · 2017: 20
- FWCI
- 106.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (publishedVersion, other-oa)
- ResearchOnline - JCU (James Cook University) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Homo Politicus (Academy of Humanities and Economics in Lodz) (submittedVersion, cc-by-nc-nd)
- Jagiellonian University Repository (Jagiellonian University) (submittedVersion, cc-by-nc-nd)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
- Funders
- Novo Nordisk
- National Institutes of Health (UL1TR001111)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- liraglutide, type 2 diabetes, renal outcomes, diabetic nephropathy, macroalbuminuria, end-stage renal disease, acute kidney injury, glucagon-like peptide-1 analogues, albuminuria, estimated glomerular filtration rate, cardiovascular risk, renal adverse effects, LEADER trial, cardiovascular outcomes, serum creatinine doubling, usual care
- MeSH terms
- Liraglutide, Aged, Albuminuria, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Double-Blind Method, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Hypoglycemic Agents, Kidney Failure, Chronic, Male, Middle Aged, Glucagon-Like Peptide 1, Intention to Treat Analysis, Acute Kidney Injury
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