Use of glucagon-like peptide-1-receptor-agonists and risk of serious renal events: Scandinavian cohort study
To assess the association between use of GLP1-receptor-agonists and risk of serious renal events in routine clinical practice.
Research Design and Methods
Cohort study using an active-comparator new-user design and nationwide register data from Sweden, Denmark and Norway, 2010-2016. The cohort included 38,731 new users of GLP1-receptor-agonists (liraglutide 92.5%; exenatide 6.2%; lixisenatide 0.7%; dulaglutide 0.6%), matched 1:1 on age, sex and propensity score to a new user of the active comparator, dipeptidyl-peptidase-4 (DPP-4) inhibitors. The main outcome was serious renal events, a composite including renal replacement therapy, death from renal causes and hospitalization for renal events. Secondary outcomes were the individual components of the main outcome. Hazard ratios (HRs) were estimated using Cox models and an intention-to-treat exposure definition. Mean (SD) follow-up time was 3.0 (1.7) years.
Mean (SD) age of the study population was 59 (10) years and 18% had cardiovascular disease. A serious renal event occurred in 570 users of GLP1-receptor-agonists (incidence rate 4.8 events per 1000 person-years) and in 722 users of DPP4 inhibitors (6.3 events per 1000 person-years; hazard ratio [HR] 0.76, 95% CI 0.68-0.85; absolute difference -1.5 [-2.1 to -0.9] events per 1000 person-years). Use of GLP1-receptor-agonists was associated with a significantly lower risk of renal replacement therapy (HR 0.73 [0.62-0.87]) and hospitalization for renal events (HR 0.73 [0.65-0.83]) but not death from renal causes (HR 0.72 [0.48-1.10]). When using an as-treated exposure definition in which patients were censored at treatment cessation or switch to the other study drug, the HR for the primary outcome was 0.60 (0.49-0.74).
ConclusionIn this large cohort of patients seen in routine clinical practice in three countries, use of GLP1-receptor-agonists, as compared with DPP4 inhibitors, was associated with a reduced risk of serious renal events.