Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial

REWIND Investigators

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)131-138
Number of pages8
JournalThe Lancet
Volume394
Issue number10193
DOIs
Publication statusPublished - 2019 Jul 13

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Type 2 Diabetes Mellitus
Randomized Controlled Trials
Placebos
Glomerular Filtration Rate
Kidney
Renal Replacement Therapy
Albumins
Creatinine
Cardiovascular Diseases
Intention to Treat Analysis
Incidence
Subcutaneous Injections
dulaglutide
Cause of Death
Stroke
Myocardial Infarction
Urine
Safety
Serum
Glucagon-Like Peptide-1 Receptor

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

@article{008e451dfd464fe48ab5e6b96b0db96f,
title = "Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial",
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.",
author = "{REWIND Investigators} and Gerstein, {Hertzel C.} and Colhoun, {Helen M.} and Dagenais, {Gilles R.} and Rafael Diaz and Mark Lakshmanan and Prem Pais and Jeffrey Probstfield and Botros, {Fady T.} and Riddle, {Matthew C.} and Lars Ryd{\'e}n and Denis Xavier and Atisso, {Charles Messan} and Leanne Dyal and Stephanie Hall and Purnima Rao-Melacini and Gloria Wong and Alvaro Avezum and Jan Basile and Namsik Chung and Ignacio Conget and Cushman, {William C.} and Edward Franek and Nicolae Hancu and Markolf Hanefeld and Shaun Holt and Petr Jansky and Matyas Keltai and Fernando Lanas and Leiter, {Lawrence A.} and Patricio Lopez-Jaramillo and {Cardona Munoz}, {Ernesto German} and Valdis Pirags and Nana Pogosova and Raubenheimer, {Peter J.} and Shaw, {Jonathan E.} and Sheu, {Wayne H.H.} and Theodora Temelkova-Kurktschiev and Mercedes Abella and Andrea Alebuena and Sandra Almagro and Eduardo Amoroso and Paula Anadon and Elizabeth Andreu and Guillermo Aristimu{\~n}o and Maria Arzadun and Maria Barbieri and Raul Barcudi and Ines Bartolacci and Gabriel Bolobanich and Anselmo Bordonava",
year = "2019",
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day = "13",
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Dulaglutide and renal outcomes in type 2 diabetes : an exploratory analysis of the REWIND randomised, placebo-controlled trial. / REWIND Investigators.

In: The Lancet, Vol. 394, No. 10193, 13.07.2019, p. 131-138.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dulaglutide and renal outcomes in type 2 diabetes

T2 - an exploratory analysis of the REWIND randomised, placebo-controlled trial

AU - REWIND Investigators

AU - Gerstein, Hertzel C.

AU - Colhoun, Helen M.

AU - Dagenais, Gilles R.

AU - Diaz, Rafael

AU - Lakshmanan, Mark

AU - Pais, Prem

AU - Probstfield, Jeffrey

AU - Botros, Fady T.

AU - Riddle, Matthew C.

AU - Rydén, Lars

AU - Xavier, Denis

AU - Atisso, Charles Messan

AU - Dyal, Leanne

AU - Hall, Stephanie

AU - Rao-Melacini, Purnima

AU - Wong, Gloria

AU - Avezum, Alvaro

AU - Basile, Jan

AU - Chung, Namsik

AU - Conget, Ignacio

AU - Cushman, William C.

AU - Franek, Edward

AU - Hancu, Nicolae

AU - Hanefeld, Markolf

AU - Holt, Shaun

AU - Jansky, Petr

AU - Keltai, Matyas

AU - Lanas, Fernando

AU - Leiter, Lawrence A.

AU - Lopez-Jaramillo, Patricio

AU - Cardona Munoz, Ernesto German

AU - Pirags, Valdis

AU - Pogosova, Nana

AU - Raubenheimer, Peter J.

AU - Shaw, Jonathan E.

AU - Sheu, Wayne H.H.

AU - Temelkova-Kurktschiev, Theodora

AU - Abella, Mercedes

AU - Alebuena, Andrea

AU - Almagro, Sandra

AU - Amoroso, Eduardo

AU - Anadon, Paula

AU - Andreu, Elizabeth

AU - Aristimuño, Guillermo

AU - Arzadun, Maria

AU - Barbieri, Maria

AU - Barcudi, Raul

AU - Bartolacci, Ines

AU - Bolobanich, Gabriel

AU - Bordonava, Anselmo

PY - 2019/7/13

Y1 - 2019/7/13

N2 - 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.

AB - 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.

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U2 - 10.1016/S0140-6736(19)31150-X

DO - 10.1016/S0140-6736(19)31150-X

M3 - Article

C2 - 31189509

AN - SCOPUS:85068568021

VL - 394

SP - 131

EP - 138

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10193

ER -