Serious renal events reduced versus DPP4 inhibitors, but not death from renal causes

The use of sodium-glucose co-transporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes significantly reduced the incidence of serious renal events compared with the use of dipeptidyl peptidase-4 (DPP4) inhibitors in routine clinical practice, nationwide register data from Sweden, Denmark and Norway has shown.

Comparing a cohort of 29,887 new users of SGLT2 inhibitors to another 29,887 new users of DPP4 inhibitors, SGLT2 inhibition reduced the risk of severe renal events by 58% compared with DPP4 inhibition at a hazard ratio (HR) of 0.42 (95% CI, 0.34-0.53), Bjorn Pasternak, MD, PhD, Karolinska Institute, Stockholm, Sweden and colleagues reported in the BMJ.

The same drug class also reduced 2 out of 3 individual components within the composite endpoint consisting of renal replacement therapy (dialysis or kidney transplantation), death from renal causes and hospital admission for renal events.

Specifically, SGLT2 inhibitors significantly lowered the need for renal replacement therapy by 68% compared to DPP4 inhibitors at a HR of 0.32 (95% CI, 0.22-0.47) as well as hospital admission for renal events by 59% at a HR of 0.41 (95%, 0.32-0.52).

In contrast, SGLT2 inhibitors did not significantly reduce death from renal causes compared with DPP4 inhibitors, investigators pointed out.

“The four large clinical trials assessing renal outcomes with SGLT2 inhibitors have included only patients at high cardiovascular risk or with established nephropathy,” the authors explained.

“The findings from this observational study complement the data from clinical trials…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,” they added.

Data from nationwide health and administrative registers in Sweden, Denmark and Norway were analyzed for the years 2013 and 2018.

“Mean follow-up time overall was 1.7…years,” researchers noted.

The mean age of the study population was 61.3 years; 19% had cardiovascular disease (CVD), and 3% had chronic kidney disease (CKD).

The SGLT2 inhibitors analyzed in the study included dapagliflozin, empagliflozin and canagliflozin.

The DPP4 inhibitors used in the study included sitagliptin, vildagliptin, linagliptin, saxagliptin and alogliptin.

Results showed that the use of a SGLT2 inhibitor significantly lowered the risk of serious renal events to 2.6 events per 1,000 person years compared with 6.2 events per 1000 person years with DPP4 inhibitor use.

“The association of SGLT2 inhibitors with lower risk of serious renal events was largely driven by the first two years of follow-up,” the authors observed, at a HR of 0.34 (95% CI, 0.25-0.47) for year 1 after study entry and a HR of 0.43 (95% CI, 0.30-0.64) for year 2.

The same drug classes also significantly lowered the need for renal replacement therapy at an incidence rate of 0.8 per 1000 person years compared with an incidence rate of 2.5 per 1000 person years for DPP4 inhibitors.

The incidence rate for hospital admission for renal events was also significantly lower at 2.0 per 1000 person years with SLGT2 inhibitors compared with 4.9 per 1000 person years for DPP4 inhibitors.

The benefits of SGLT2 inhibition were also seen in men and women, across different age groups and individual drugs although the reduction in the risk of serious renal events was greater in patients with CVD and those with CKD, as would be predicted by clinical trial results.

Limitations of the study include the fact that it was carried out in Scandinavia and the generalizability of the findings to other populations and healthcare systems is unknown.

Well Designed Study

Commenting on the findings, Steven Smith, PharmD, MPH, University of Florida in Gainesville, Florida, noted that results from this well-designed study add new evidence that SGLT2 inhibitors may be preferable to DPP4 inhibitors in patients at risk for, or who already have, diabetic kidney disease.

“Evidence is mixed regarding whether DPP4 inhibitors prevent progression of diabetic kidney disease, but they do not worsen it,” Smith wrote.

“[And] the protective effect of SGLT2 inhibitors seems to occur independent of improved hyperglycemic control and probably independent of other effects shared by DPP4 inhibitors (such as reduced blood pressure or weight loss),” he suggested.

Smith also noted that the SGLT2 inhibitors lowered the risk of the development and progression of diabetic kidney disease in patients without CVD or CKD.

This finding, he wrote, was very informative as these lower risk types of patients had been largely excluded from clinical trials.

Nevertheless, Smith suggested that additional trials in real world settings and in more diverse populations “could add further support for broader access to these drugs, not just in high income countries, but also in lower income countries where the burden of kidney disease is disproportionately high,” he concluded.

  1. The sodium-glucose co-transporter 2 (SGLT2) inhibitors significantly reduced the incidence of serious renal events compared to the dipeptidyl peptidase-4 (DPP4) inhibitors in patients with type 2 diabetes.

  2. The previously reported renoprotective effects of the SGLT2 inhibitors have now been shown in routine clinical care in patients who were not at high risk for cardiovascular disease and who did not have chronic kidney disease.

Pam Harrison, Contributing Writer, BreakingMED™

Pasternak had no conflicts of interest to declare.

Cat ID: 13

Topic ID: 76,13,730,13,192,918