Sodium-glucose co-transporter 2 (SGLT2) inhibitors are associated with lower risk of serious renal events than dipeptidyl peptidase-4 (DPP4) inhibitors in real-world patients with type 2 diabetes and various levels of renal function, according to new data from Sweden, Denmark, and Norway.

Investigators used nationwide registry data to propensity-score match 29,887 new users of SLGT2 inhibitors (mostly dapagliflozin and empagliflozin; canagliflozin use was rare) to 29,887 new users of DPP-4 inhibitors on 57 variables. Use of SGLT2 inhibitors was significantly associated with a 58% reduced relative risk of serious renal events (a composite of renal replacement therapy [RRT], death from renal causes, and hospitalization for renal events) and an absolute risk reduction of 3.6 events per 1000 person years (2.6 vs 6.2 events per 1000 person years, respectively), Peter Ueda, MD, PhD, of Karolinska Institutet in Stockholm, Sweden, and collaborators reported in BMJ. By individual component of the composite end point, use of SGLT2 inhibitors was significantly associated with a 68% and 59% lower risk for RRT and hospital admission for renal events, respectively, and a nonsignificant 23% lower risk for death from renal causes. The corresponding absolute risk reductions were −1.7 vs −2.9 vs −0.1 events per 1000 person years, respectively.

In subgroup analyses, the decreased risk of the composite end point associated with SGLT2 inhibitors was significantly greater among patients with than without chronic kidney disease (70% vs 48%) and in those with than without cardiovascular disease (82% vs 48%).

“Although the absolute risk reduction associated with SGLT2 inhibitors was larger in patients with cardiovascular disease or chronic kidney disease, the protective association of SGLT2 inhibitors was also observed in patients without such history,” Dr Ueda’s team stated.


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“The findings from this observational study complement the data from clinical trials, as well as our previous observational study of cardiovascular outcomes, and provide further support for the use of SGLT2 inhibitors across a broad range of patients with type 2 diabetes with various levels of renal function.”

In sensitivity analyses, the protective effect of SGLT2 inhibitors appeared independent from hyperglycemic control, reduced blood pressure, and weight loss. According to the authors, SGLT2 inhibitors may have favorable effects on renal hemodynamics and may reduce tissue inflammation and fibrosis.

In an accompanying editorial, Steven M. Smith, PharmD, MPH, of the University of Florida in Gainesville, praised the study while acknowledging that it is observational and subject to some confounding.

“Overall, the findings by Pasternak and colleagues add to the impressive track record for SGLT2 inhibitors. Additional pragmatic comparative effectiveness trials in real world settings and more diverse populations could add further support for broader access to these drugs, not only in high income countries but also in lower income countries where the burden of kidney disease is disproportionately high.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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References

Pasternak B, Wintzell V, Melbye M, et al. Use of sodium-glucose co-transporter 2 inhibitors and risk of serious renal events: Scandinavian cohort study [published April 29, 2020]. BMJ 2020;369:m1186. doi: 10.1136/bmj.m1186

Smith SM. SGLT2 inhibitors and kidney outcomes in the real world: Observational data from clinical practice favour these drugs over DPP4 inhibitors [published April 29, 2020]. BMJ 2020;369:m1584. doi: 10.1136/bmj.m1584