GLP-1 receptor agonist versus DPP-4 inhibitor and kidney and cardiovascular outcomes in clinical practice in type-2 diabetes

Whether glucagon-like peptide-1 receptor agonists (GLP1RA) reduce detrimental kidney outcomes is uncertain. In secondary analyses, trials have shown consistent reductions in macroalbuminuria, but inconclusive results about kidney function decline. To help clarify this, we conducted a cohort study to compare kidney and cardiovascular outcomes in individuals who started GLP1RA or dipeptidyl peptidase-4 inhibitors (DPP4i) (reduces degradation of endogenous GLP1). The primary outcome was a composite of sustained doubling of creatinine, kidney failure or kidney death. The secondary outcomes were three-point major adverse cardiovascular events (MACE) and its individual components. Propensity score weighted Cox regression was used to balance 53 confounders. A total of 19,766 individuals were included, of whom 5,699 initiated GLP1-RA, and were followed for a median 2.9 years. Mean age was 63 years, 26.2% had atherosclerotic cardiovascular disease and 16.0% had an estimated glomerular filtration rate (eGFR) under 60 ml/ min/1.73m(2). The adjusted hazard ratio for GLP1-RA vs. DPP4i was 0.72 (95% confidence interval 0.53-0.98) for the composite kidney outcome and 0.85 (0.73-0.99) for MACE, with absolute five-year risk reductions of 0.8% (0.1%-1.5%) and 1.6% (0.2%-2.9%), respectively. Hazard ratios were 0.79 (0.60-1.05) for cardiovascular death, 0.86 (0.68-1.09) for myocardial infarction and 0.74 (0.59-0.93) for stroke. Results were consistent within subgroups, including age, sex, eGFR and baseline metformin use. Thus, in our analysis of patients from routine clinical practice, the use of GLP1RA was associated with a lower risk of kidney outcomes compared with DPP4i. Reductions in both kidney outcomes and MACE were similar in magnitude to those reported in large cardiovascular outcome trials.

Automated summary

In this study, it was found that glucagon-like peptide-1 receptor agonists (GLP1RA) were associated with a lower risk of kidney outcomes compared to dipeptidyl peptidase-4 inhibitors (DPP4i). The reductions in both kidney outcomes and major adverse cardiovascular events (MACE) were similar in magnitude to those reported in large cardiovascular outcome trials.