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<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. Copyright (c) 2019 Elsevier Ltd. All
rights reserved.
