Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial - PubMed (original) (raw)
Randomized Controlled Trial
. 2019 Jul 13;394(10193):131-138.
doi: 10.1016/S0140-6736(19)31150-X. Epub 2019 Jun 9.
Helen M Colhoun 2, Gilles R Dagenais 3, Rafael Diaz 4, Mark Lakshmanan 5, Prem Pais 6, Jeffrey Probstfield 7, Fady T Botros 5, Matthew C Riddle 8, Lars Rydén 9, Denis Xavier 6, Charles Messan Atisso 5, Leanne Dyal 10, Stephanie Hall 10, Purnima Rao-Melacini 10, Gloria Wong 10, Alvaro Avezum 11, Jan Basile 12, Namsik Chung 13, Ignacio Conget 14, William C Cushman 15, Edward Franek 16, Nicolae Hancu 17, Markolf Hanefeld 18, Shaun Holt 19, Petr Jansky 20, Matyas Keltai 21, Fernando Lanas 22, Lawrence A Leiter 23, Patricio Lopez-Jaramillo 24, Ernesto German Cardona Munoz 25, Valdis Pirags 26, Nana Pogosova 27, Peter J Raubenheimer 28, Jonathan E Shaw 29, Wayne H-H Sheu 30, Theodora Temelkova-Kurktschiev 31; REWIND Investigators
Collaborators, Affiliations
- PMID: 31189509
- DOI: 10.1016/S0140-6736(19)31150-X
Randomized Controlled Trial
Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial
Hertzel C Gerstein et al. Lancet. 2019.
Abstract
Background: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease.
Methods: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952.
Findings: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p<0·0001), with HRs of 0·89 (0·78-1·01; p=0·066) for sustained decline in eGFR of 30% or more and 0·75 (0·39-1·44; p=0·39) for chronic renal replacement therapy.
Interpretation: Long-term use of dulaglutide was associated with reduced composite renal outcomes in people with type 2 diabetes.
Funding: Eli Lilly and Company.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Comment in
- Is it time to REWIND the cardiorenal clock in diabetes?
Verma S, Mazer CD, Perkovic V. Verma S, et al. Lancet. 2019 Jul 13;394(10193):95-97. doi: 10.1016/S0140-6736(19)31267-X. Epub 2019 Jun 9. Lancet. 2019. PMID: 31189510 No abstract available. - Dulaglutide slows kidney disease in type 2 diabetes.
Oliva-Damaso N, Oliva-Damaso E, Payan J, Porrini E. Oliva-Damaso N, et al. Lancet. 2020 Feb 22;395(10224):559. doi: 10.1016/S0140-6736(19)32550-4. Lancet. 2020. PMID: 32087784 No abstract available.
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