SGLT2 inhibitors reduce risk of serious renal events

Use of sodium-glucose co-transporter 2 (SGLT2) inhibitors appears to significantly lower the risk of serious renal events as compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, according to a study.

“Complementing data from clinical trials, this study provides further support for the use of SGLT2 inhibitors in a broad range of patients with type 2 diabetes (T2D),” the researchers said.

This analysis using nationwide data from Sweden, Denmark and Norway from 2013 to 2018 included a cohort of 29,887 new users of SGLT2 inhibitors (follow-up time: dapagliflozin, 66.1 percent; empagliflozin, 32.6 percent; canagliflozin, 1.3 percent) and 29,887 new users of an active comparator (DPP-4 inhibitors) matched 1:1 based on a propensity score with 57 variables.

Mean follow-up was 1.7 years. Primary endpoints were serious renal events and a composite including renal replacement therapy, death from renal causes and hospital admission for renal events, while secondary ones included the individual components of the primary outcome.

Of the participants (mean age, 61.3 years), 11,108 (19 percent) had cardiovascular disease and 1,974 (3 percent) had chronic kidney disease. Use of SGLT2 vs DPP-4 inhibitors resulted in a reduced risk of serious renal events (2.6 vs 6.2 events per 1,000 person-years; hazard ratio [HR, 95 percent confidence interval [CI], 0.34–0.53; absolute difference, –3.6, 95 percent CI, –4.4 to –2.8 events per 1,000 person-years). [BMJ 2020;369:m1186]

Secondary outcome analyses also revealed that the use of SGLT2 vs DPP-4 inhibitors was associated with a lower risk of renal replacement therapy (HR, 0.32, 95 percent CI, 0.22–0.47), hospital admission for renal events (HR, 0.41, 95 percent CI, 0.32–0.52) and death from renal causes (HR, 0.77, 95 percent CI, 0.26–2.23).

Adjustments were made in the model in sensitivity analyses in each of the Swedish and Danish parts of the cohort for glycated haemoglobin and estimated glomerular filtration rate (Sweden and Denmark) and for blood pressure, body mass index and smoking (Sweden only). These analyses showed that the HR moved from 0.41 (95 percent CI, 0.26–0.66) to 0.50 (95 percent CI, 0.31–0.81) in Sweden and from 0.42 (95 percent CI, 0.32–0.56) to 0.55 (95 percent CI, 0.41–0.74) in Denmark.

In large clinical trials, SGLT2 inhibitors have been shown to reduce the risk of advanced renal outcomes, including renal replacement therapy, and protect kidney functions in patients at high risk of cardiovascular disease or established nephropathy. [N Engl J Med 2019;380:2295-2306; Lancet Diabetes Endocrinol 2018;6:691-704; N Engl J Med 2016;375:323-334; Lancet Diabetes Endocrinol 2019;7:606-617; Lancet Diabetes Endocrinol 2019;2:1-10]

“The findings from [the current] 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 T2D with various levels of renal function,” the researchers said. [N Engl J Med 2019;380:2295-2306; Lancet Diabetes Endocrinol 2018;6:691-704; N Engl J Med 2016;375:323-334; Lancet Diabetes Endocrinol 2019;7:606-617; BMJ 2019;366:l4772]

In addition, “SGLT2 inhibitors have been suggested to protect the kidney through several mechanisms, including favourable effects on renal haemodynamics and reduction of tissue inflammation and fibrosis,” they added. [Lancet Diabetes Endocrinol 2019;7:397-412; Circulation 2016;134:752-772]