Target Trial Emulation: Glucagon-Like Peptide-1 Receptor Agonist, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors for Kidney Outcome Prevention.

key pointsUnknown if addition of newer diabetes medications is associated with kidney disease among older patients who were under recruited in clinical trials. In this target trial emulation, we report a protective association for kidney events and death for both glucagon-like peptide 1 receptor agonist and sodium-glucose cotransporter 2 inhibitor, compared with dipeptidyl peptidase-4 inhibitor. The association of glucagon-like peptide 1 receptor agonist and sodium-glucose cotransporter 2 inhibitor on kidney disease extended across multiple subgroups including short duration of use and in the older population.

backgroundA trial emulation approach evaluated kidney outcomes for addition of three diabetes medications among Veterans, including older Veterans underrepresented in trials.

methodsA retrospective cohort of Veterans with diabetes who were new users adding glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter 2 inhibitors (SGLT2is), or dipeptidyl peptidase-4 inhibitors (DPP4is). Each group was followed until a composite of death or kidney event defined as a 50% decline in eGFR, kidney failure (transplant or dialysis) or censored for nonpersistence of drug class, loss of follow-up, and study end. The primary analysis used propensity score weights to compare the hazard of the composite outcome. The secondary analysis considered cause-specific hazard of kidney events with death as censoring. An Aalen-Johansen plot displayed individual outcomes of kidney event or death as a competing risk. Subgroup analyses evaluated Veterans by duration of use, age, eGFR, and urine protein.

resultsAfter propensity score weighting, the cohort included 42,684 GLP-1 RA, 44,198 SGLT2i, and 44,213 DPP4i episodes. The median age was 69 years, diabetes duration was 10.6 years (6.8-15.2), and eGFR was 75 ml/min per 1.73 m 2 (58-92). Event rates per 1000 person-years were 34.6 (33.3-36.0) versus 29.0 (27.8-30.3) versus 47.4 (46.0-48.9) for GLP-1 RA, SGLT2i, and DPP4i, respectively. There was a protective association for composite of kidney event and death for GLP-1 RA, hazard ratio (HR) 0.70 (0.67 to 0.74), and SGLT2i users (HR, 0.65 [0.61 to 0.68]) versus DPP4i. The results were similar for the cause-specific hazard of kidney event alone GLP-1 RA (HR, 0.72 [0.65 to 0.80]) and SGLT2i (HR, 0.48 [0.43 to 0.55]) and for subgroups.

conclusionsGLP-1 RA and SGLT2i as add-on diabetes treatment were associated with lower composite and individual outcomes of kidney event and death. The association was similar across subgroups highlighting the value in primary prevention among older populations.