SGLT-2 inhibitors associated with fewer serious renal events than DPP-4 inhibitors

In a propensity-matched Scandinavian study, new users of sodium-glucose cotransporter-2 (SGLT-2) inhibitors had a lower risk of renal replacement therapy and hospital admission for renal events than new users of dipeptidyl peptidase-4 (DPP-4) inhibitors.


Use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors was associated with a lower risk of serious renal events compared to use of dipeptidyl peptidase-4 (DPP-4) inhibitors in a recent study.

Researchers used nationwide registry data from 2013 through 2018 from Sweden, Denmark, and Norway to assess serious renal events in routine clinical practice. The main outcome was a composite of renal replacement therapy, death from renal causes, and hospital admission for renal events. Secondary outcomes were the individual components of the main outcome. Results were published online on April 29 by The BMJ.

Overall, the cohort study included 29,887 new users of SGLT-2 inhibitors (dapagliflozin, 66.1%; empagliflozin, 32.6%; canagliflozin, 1.3%) and 29,887 new users of an active comparator, DPP-4 inhibitors, matched 1:1 on the basis of a propensity score with 57 variables, such as sociodemographic characteristics, comorbidities, co-medications, and health care utilization. The mean age of the study population was 61.3 years (SD, 10.5 years), and the mean follow-up time was 1.7 years (SD, 1.0 years). About 19% of patients had cardiovascular disease, and about 3% had chronic kidney disease. Compared with use of DPP-4 inhibitors, use of SGLT-2 inhibitors was associated with a reduced risk of serious renal events (2.6 events per 1,000 person-years vs. 6.2 events per 1,000 person-years; hazard ratio, 0.42 [95% CI, 0.34 to 0.53]; absolute difference, −3.6 [95% CI, −4.4 to −2.8] events per 1,000 person-years). In secondary outcome analyses, the hazard ratios for use of SGLT-2 inhibitors versus DPP-4 inhibitors were 0.32 (95% CI, 0.22 to 0.47) for renal replacement therapy, 0.41 (95% CI, 0.32 to 0.52) for hospital admission for renal events, and 0.77 (95% CI, 0.26 to 2.23) for death from renal causes.

Among other limitations, the study defined exposure based on filled prescriptions, and low adherence could bias the results toward the null, the study authors said. In addition, the generalizability of the results to populations and health care systems outside Scandinavia is unknown, they noted.

The study results should be interpreted with some caution, as sensitivity analyses suggested a modest degree of unmeasured confounding in the primary analysis, an accompanying editorial said. However, the findings “add to the impressive track record for SGLT2 inhibitors,” the editorialist wrote. “Additional pragmatic comparative effectiveness trials in real world settings and more diverse populations could add further support for broader access to these drugs.”