Changes in albuminuria predict cardiovascular and renal outcomes in type 2 diabetes: a post Hoc analysis of the LEADER trial
Open accessAbstract
OBJECTIVE: A post hoc analysis to investigate the association between 1-year changes in albuminuria and subsequent risk of cardiovascular and renal events. RESEARCH DESIGN AND METHODS: LEADER was a randomized trial of liraglutide up to 1.8 mg/day versus placebo added to standard care for 3.5–5 years in 9,340 participants with type 2 diabetes and high cardiovascular risk. We calculated change in urinary albumin-to-creatinine ratio (UACR) from baseline to 1 year in participants with >30% reduction (n = 2,928), 30–0% reduction (n = 1,218), or any increase in UACR (n = 4,124), irrespective of treatment. Using Cox regression, risks of major adverse cardiovascular events (MACE) and a composite nephropathy outcome (from 1 year to end of trial in subgroups by baseline UACR [<30 mg/g, 30–300 mg/g, or ≥300 mg/g]) were assessed. The analysis was adjusted for treatment allocation alone as a fixed factor and for baseline variables associated with cardiovascular and renal outcomes. RESULTS: For MACE, hazard ratios (HRs) for those with >30% and 30–0% UACR reduction were 0.82 (95% CI 0.71, 0.94; P = 0.006) and 0.99 (0.82, 1.19; P = 0.912), respectively, compared with any increase in UACR (reference). For the composite nephropathy outcome, respective HRs were 0.67 (0.49, 0.93; P = 0.02) and 0.97 (0.66, 1.43; P = 0.881). Results were independent of baseline UACR and consistent in both treatment groups. After adjustment, HRs were significant and consistent in >30% reduction subgroups with baseline micro- or macroalbuminuria. CONCLUSIONS: A reduction in albuminuria during the 1st year was associated with fewer cardiovascular and renal outcomes, independent of treatment. Albuminuria monitoring remains an important part of diabetes care, with great unused potential.
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In an analysis of LEADER, a reduction in albuminuria during the first year of treatment was associated with fewer cardiovascular and kidney outcomes; patients who had a >30% reduction in UACR experienced an 18% lower risk of MACE (HR 0.82) and 33% reduced risk for the composite kidney outcome (HR 0.67) regardless of baseline UACR or treatment arm.
“Another analysis of the LEADER trial found that a reduction in albuminuria during the first year of treatment was associated with fewer cardiovascular and kidney outcomes; patients who had a >30% reduction in UACR experienced an 18% lower risk of MACE [HR, 0.82 (0.71–0.74)] and 33% reduced risk for the composite kidney outcome [HR, 0.67 (0.49–0.93)] regardless of baseline UACR or treatment arm [53”
From Glucagon-like peptide-1 receptor agonists in diabetic kidney disease: a review of their kidney and heart protection (2023) · cites this paper as [53]
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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 · cited 13× · see citing works
“Data from a number of trials have indicated that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) lower albuminuria andprovide CVand renal benefits in participants with type 2 diabetes (T2D) (8–12).”
BackgroundMethodInfluentialSelf-citationSemaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M. L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1607141 · Cited by 6,900 · cited 1× · see citing works
“Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) and Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN 6) trials (9; 13).”
BackgroundSelf-citationMACMAHON, S. (1990) · The Lancet · doi:10.1016/0140-6736(90)90878-9 · Cited by 4,253 · cited 1× · see citing works
“We assessed the impact of regression to the mean by calculating the nonparametric regression dilution coefficient using theMacMahon-Petomethod, dividing UACRdata intodeciles (18) (Supplementary”
MethodGerstein, H. C. (2001) · JAMA · doi:10.1001/jama.286.4.421 · Cited by 2,440 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2022</i>
American Diabetes Association Professional Practice Committee (2022) · Diabetes Care · doi:10.2337/dc22-s009 · Cited by 1,555 · see citing works
Liraglutide and renal outcomes in type 2 diabetes
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. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1616011 · Cited by 1,253 · see citing works
Self-citationRosenstock, J., Perkovic, V., Johansen, O. E., Cooper, M. E., Kahn, S. E., Marx, N., Alexander, J. H., Pencina, M., Toto, R. D., Wanner, C., et al. (2019) · JAMA · doi:10.1001/jama.2018.18269 · Cited by 1,084 · see citing works
de Zeeuw, D., Remuzzi, G., Parving, H., Keane, W. F., Zhang, Z., Shahinfar, S., Snapinn, S., Cooper, M. E., Mitch, W. E., & Brenner, B. M. (2004) · Kidney International · doi:10.1111/j.1523-1755.2004.00653.x · Cited by 963 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2020</i>
American Diabetes Association (2020) · Diabetes Care · doi:10.2337/dc20-s009 · Cited by 914 · see citing works
de Zeeuw, D., Remuzzi, G., Parving, H., Keane, W. F., Zhang, Z., Shahinfar, S., Snapinn, S., Cooper, M. E., Mitch, W. E., & Brenner, B. M. (2004) · Circulation · doi:10.1161/01.cir.0000139860.33974.28 · Cited by 748 · see citing works
Tuttle, K. R., Lakshmanan, M. C., Rayner, B., Busch, R. S., Zimmermann, A. G., Woodward, D. B., & Botros, F. T. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30104-9 · Cited by 648 · see citing works
Gerstein, H. C., Colhoun, H. M., Dagenais, G. R., Diaz, R., Lakshmanan, M., Pais, P., Probstfield, J., Botros, F. T., Riddle, M. C., Rydén, L., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)31150-x · Cited by 638 · see citing works
Self-citationHeerspink, H. J. L., Greene, T., Tighiouart, H., Gansevoort, R. T., Coresh, J., Simon, A. L., Chan, T. M., Hou, F. F., Lewis, J. B., Locatelli, F., et al. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30314-0 · Cited by 397 · see citing works
Self-citationAtkins, R. C., Briganti, E. M., Lewis, J. B., Hunsicker, L. G., Braden, G. L., de Crespigny, P. J. C., Deferrari, G., Drury, P., Locatelli, F., Wiegmann, T. B., et al. (2005) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2004.10.019 · Cited by 366 · see citing works
Coresh, J., Heerspink, H. J. L., Sang, Y., Matsushita, K., Arnlov, J., Astor, B. C., Black, C., Brunskill, N. J., Carrero, J.-J., Feldman, H. I., et al. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30313-9 · Cited by 338 · see citing works
Self-citationEijkelkamp, W. B. A., Zhang, Z., Remuzzi, G., Parving, H., Cooper, M. E., Keane, W. F., Shahinfar, S., Gleim, G. W., Weir, M. R., Brenner, B. M., et al. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006050445 · Cited by 299 · see citing works
Tuttle, K. R., Alicic, R. Z., Duru, O. K., Jones, C. R., Daratha, K. B., Nicholas, S. B., McPherson, S. M., Neumiller, J. J., Bell, D. S., Mangione, C. M., et al. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.18169 · Cited by 275 · see citing works
Changes in Albuminuria Predict Mortality and Morbidity in Patients with Vascular Disease
Schmieder, R. E., Mann, J. F. E., Schumacher, H., Gao, P., Mancia, G., Weber, M. A., McQueen, M., Koon, T., & Yusuf, S. (2011) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010091001 · Cited by 270 · see citing works
Self-citationEffect of Saxagliptin on Renal Outcomes in the SAVOR-TIMI 53 Trial
Mosenzon, O., Leibowitz, G., Bhatt, D. L., Cahn, A., Hirshberg, B., Wei, C., Im, K., Rozenberg, A., Yanuv, I., Stahre, C., et al. (2016) · Diabetes Care · doi:10.2337/dc16-0621 · Cited by 267 · see citing works
Self-citationMuskiet, M. H. A., Tonneijck, L., Huang, Y., Liu, M., Saremi, A., Heerspink, H. J. L., & van Raalte, D. H. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30268-7 · Cited by 259 · see citing works
Self-citationMarso, S. P., Poulter, N. R., Nissen, S. E., Nauck, M. A., Zinman, B., Daniels, G. H., Pocock, S., Steinberg, W. M., Bergenstal, R. M., Mann, J. F. E., et al. (2013) · American Heart Journal · doi:10.1016/j.ahj.2013.07.012 · Cited by 244 · see citing works
Self-citationDrug-Induced Reduction in Albuminuria Is Associated with Subsequent Renoprotection: A Meta-Analysis
Lambers Heerspink, H. J., Kröpelin, T. F., Hoekman, J., & de Zeeuw, D. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014070688 · Cited by 242 · see citing works
Pollock, C., Stefánsson, B., Reyner, D., Rossing, P., Sjöström, C. D., Wheeler, D. C., Langkilde, A. M., & Heerspink, H. J. L. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30086-5 · Cited by 205 · see citing works
Self-citationComparison of different measures of urinary protein excretion for prediction of renal events
Lambers Heerspink, H. J., Gansevoort, R. T., Brenner, B. M., Cooper, M. E., Parving, H. H., Shahinfar, S., & de Zeeuw, D. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010010063 · Cited by 193 · see citing works
Groop, P., Cooper, M. E., Perkovic, V., Hocher, B., Kanasaki, K., Haneda, M., Schernthaner, G., Sharma, K., Stanton, R. C., Toto, R. D., et al. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13041 · Cited by 149 · see citing works
The effect of liraglutide on renal function: A randomized clinical trial
von Scholten, B. J., Persson, F., Rosenlund, S. V., Hovind, P. H., Faber, J. O., Hansen, T. W., & Rossing, P. R. (2016) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12808 · Cited by 105 · see citing works
Self-citationEshøj, O., Feldt‐Rasmussen, B., Larsen, M., et al. (1987) · Diabetic Medicine · doi:10.1111/j.1464-5491.1987.tb00924.x · Cited by 102 · see citing works
Time course and mechanisms of the anti‐hypertensive and renal effects of liraglutide treatment
von Scholten, B. J., Lajer, M., Goetze, J. P., Persson, F., & Rossing, P. (2015) · Diabetic Medicine · doi:10.1111/dme.12594 · Cited by 73 · see citing works
Self-citationChanges in Albuminuria and the Risk of Major Clinical Outcomes in Diabetes: Results From ADVANCE-ON
Jun, M., Ohkuma, T., Zoungas, S., Colagiuri, S., Mancia, G., Marre, M., Matthews, D. R., Poulter, N. R., Williams, B., Rodgers, A., et al. (2017) · Diabetes Care · doi:10.2337/dc17-1467 · Cited by 59 · see citing works
Heerspink, H. J. L., Ninomiya, T., Persson, F., Brenner, B. M., Brunel, P., Chaturvedi, N., Desai, A. S., Haffner, S. M., McMurray, J. J. V., Solomon, S. D., et al. (2015) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12600 · Cited by 57 · see citing works
Self-citationHeerspink, H. J. L., Persson, F., Brenner, B. M., Chaturvedi, N., Brunel, P., McMurray, J. J. V., Desai, A. S., Solomon, S. D., Pfeffer, M. A., PARVING, H.-H. D., et al. (2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00469-6 · Cited by 49 · see citing works
Self-citationNumber and Frequency of Albuminuria Measurements in Clinical Trials in Diabetic Nephropathy
Kröpelin, T. F., de Zeeuw, D., Andress, D. L., Bijlsma, M. J., Persson, F., Parving, H., & Heerspink, H. J. L. (2015) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.07780814 · Cited by 26 · see citing works
Self-citationZobel, E. H., von Scholten, B. J., Lindhardt, M. K., Persson, F., Hansen, T. W., & Rossing, P. R. (2016) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2016.09.016 · Cited by 14 · see citing works
Self-citationChanges in albuminuria and renal outcome in patients with type 2 diabetes and hypertension
Viazzi, F., Ceriello, A., Fioretto, P., et al. (2018) · Journal of Hypertension · doi:10.1097/hjh.0000000000001749 · Cited by 11 · see citing works
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Rossing, P., Baeres, F. M. M., Bakris, G., Bosch-Traberg, H., Gislum, M., Gough, S. C. L., Idorn, T., Lawson, J., Mahaffey, K. W., Mann, J. F. E., et al. (2023) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfad009 · Cited by 242 · see citing works
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- Authors
- Persson, F., Bain, S. C., Mosenzon, O., Heerspink, H. J. L., Mann, J. F. E., Pratley, R., Raz, I., Idorn, T., Rasmussen, S., von Scholten, B. J., & Rossing, P.
- Affiliations
- Steno Diabetes Center Copenhagen (DK)
- Swansea University (GB)
- Hebrew University of Jerusalem (IL)
- University Medical Center Groningen (NL)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- AdventHealth Orlando (US)
- Novo Nordisk (Denmark) (DK)
- Novo Nordisk A/S, Søborg, Denmark
- University of Copenhagen (DK)
- Corresponding author
- Persson, Frederik
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2021-01-27
- Volume
- 44
- Issue
- 4
- Pages
- 1020-1026
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC7985419
- OpenAlex
- W3118994355
- Cited by
- 71
- References
- 34
- Citations by year
- 2026: 15 · 2025: 15 · 2024: 13 · 2023: 14 · 2022: 9 · 2021: 5
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Care (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- Cronfa (Swansea University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- Teva Pharmaceutical Industries
- Celgene
- National Institute for Health and Care Excellence
- Janssen Scientific Affairs
- Steno Diabetes Center Copenhagen (SDCC 3.A Complications)
- European Commission
- Cardiff University
- Hebrew University of Jerusalem
- Eisai
- Novo Nordisk
- Astellas Pharma
- Vifor Pharma
- Servier
- Canadian Institutes of Health Research
- Relypsa
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- albuminuria, albumin-creatinine ratio, type 2 diabetes, liraglutide, major adverse cardiovascular events, diabetic nephropathy, renal outcomes, cardiovascular outcomes, microalbuminuria, macroalbuminuria, LEADER trial
- MeSH terms
- Liraglutide, Albuminuria, Creatinine, Diabetes Mellitus, Type 2, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases
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