medwireNews: People with type 2 diabetes have a lower risk for chronic kidney disease (CKD) progression and death when using sodium-glucose cotransporter (SGLT)2 inhibitors than when given dipeptidyl peptidase (DPP)-4 inhibitors, real-world study data show.
The research, by Iskandar Idris (University of Nottingham, UK) and colleagues, was based on English primary care practice data for 131,824 people with type 2 diabetes, the majority (79.0%) of whom had no known history of CKD.
Using propensity score matching, the researchers paired 23,438 people who initiated SGLT2 inhibitor therapy between 2013 and 2018 with the same number of individuals who began DPP-4 inhibitors on the basis of age, sex, presence of microvascular complications, frailty, and cardiovascular comorbidity.
Prior to matching, the team found that patients given an SGLT2 inhibitor were younger, less frail, had lower burden of heart failure and CKD, a higher estimated glomerular filtration rate (eGFR) and glycated hemoglobin (HbA1c) level, and were more likely to be using glucose-lowering drugs except sulfonylureas.
During a median 2.1 years of follow-up, 359 individuals in the SGLT2 inhibitor group experienced the primary composite CKD endpoint of a more than 40% decline in eGFR, end-stage kidney disease (ESKD; a composite of kidney transplantation, maintenance of dialysis, sustained low eGFR<15, or diagnosis of ESKD), or kidney death.
By comparison, there were 568 CKD events in the DPP-4 inhibitor group, and the corresponding rates of 7.48 versus 11.77 events per 1000 patient–years were significantly different between the two groups, with a hazard ratio (HR) of 0.64 in favor of SGLT2 inhibition.
The risks for all-cause mortality, ESKD, and a sustained low eGFR were also significantly lower with SGLT2 inhibition than with DPP-4 inhibition, at HRs of 0.74, 0.37, and 0.33, respectively, as was the risk for a 40% or greater decline in eGFR (HR=0.66) and the likelihood of being diagnosed with ESKD in primary care (HR=0.04).
Idris and co-authors report in Diabetes, Obesity and Metabolism that the findings were consistent across subgroups, with the notable exception that mortality differences between the two treatment groups were only apparent for people with an HbA1c below 7.0%. Conversely, the relative risk reduction in the composite CKD endpoint was independent of baseline glucose control.
In post-hoc analyses, they observed that eGFR values were stable or increased over time among patients on SGLT2 inhibitors but decreased among those patients receiving DPP-4 inhibitors.
Idris and team conclude that their “findings complement and are consistent with [randomized controlled trials] and observational studies investigating the effectiveness of SGLT [inhibitors] compared with other glucose lowering therapies to reduce cardio-renal endpoints.”
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