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

Published on Jul 1, 2019in The Lancet59.102
· DOI :10.1016/S0140-6736(19)31150-X
Hertzel C. Gerstein93
Estimated H-index: 93
(Population Health Research Institute),
Helen M. Colhoun50
Estimated H-index: 50
(Edin.: University of Edinburgh)
+ 1453 AuthorsWilliam Zigrang2
Estimated H-index: 2
Sources
Abstract
Summary 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 m 2 (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 Interpretation Long-term use of dulaglutide was associated with reduced composite renal outcomes in people with type 2 diabetes. Funding Eli Lilly and Company.
  • References (27)
  • Citations (18)
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References27
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#1Hertzel C. Gerstein (Population Health Research Institute)H-Index: 93
#2Helen M. Colhoun (Edin.: University of Edinburgh)H-Index: 50
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#2Stephen D. Wiviott (Brigham and Women's Hospital)H-Index: 67
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Background: Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose contransporter-2 inhibitors (SGLT2i) have emerged as two new classes of antihyperglycemic agents that also reduce cardiovascular risk. The relative benefits in patients with and without established atherosclerotic cardiovascular disease (ASCVD) for different outcomes with these classes of drugs remain undefined. Methods: We performed a systematic review and trial-level meta-analysis of GLP1-RA and SGLT2i cardiovas...
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#1Marcel H.A. Muskiet (VUmc: VU University Medical Center)H-Index: 14
#2Lennart Tonneijck (VUmc: VU University Medical Center)H-Index: 15
Last. Daniël H. van Raalte (VUmc: VU University Medical Center)H-Index: 21
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Summary Background The results of the ELIXA trial demonstrated the cardiovascular safety of lixisenatide, a short-acting glucagon-like peptide-1 receptor agonist, in patients with type 2 diabetes and acute coronary syndrome. In this exploratory analysis of ELIXA, we investigate the effect of lixisenatide on renal outcomes. Methods ELIXA was a randomised, double-blind, placebo-controlled trial, done at 828 sites in 49 countries. Patients with type 2 diabetes and a recent coronary artery event wer...
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The aim was to determine the effects of dulaglutide, a synthetic once-weekly, injectable human glucagon-like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglu...
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Approximately 20% to 40% of patients with type 1 or type 2 diabetes mellitus develop diabetic kidney disease. This is a clinical syndrome characterized by persistent albuminuria (> 300 mg/24 h, or > 300 mg/g creatinine), a relentless decline in glomerular filtration rate (GFR), raised arterial blood pressure, and enhanced cardiovascular morbidity and mortality. There is a characteristic histopathology. In classical diabetic nephropathy, the first clinical sign is moderately increased urine album...
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