In an observational analysis of pooled national registry data from Scandinavia, SGLT2 inhibitors were associated with a reduced risk of serious renal events compared with dipeptidyl peptidase-4 (DPP4) inhibitors, consistent with the results of previous clinical trials and smaller observational studies.
The researchers who carried out the study, published in the BMJ, say their findings provide further support for the use of SGLT2 inhibitors 'across a broad range of patients with type II diabetes with various levels of renal function'. A linked editorial in the BMJ says the study 'adds new evidence that SGLT2 inhibitors seem preferable to DPP4 inhibitors in patients at risk of developing or worsening diabetic kidney disease'.
SGLT2 inhibitors have been suggested to protect the kidney via several mechanisms, including favourable effects on renal haemodynamics and reduction of tissue inflammation and fibrosis.
Using national registry data from Sweden, Denmark, and Norway, the researchers matched new users of SGLT2 inhibitors (n=29,887) to new users of DPP4 inhibitors (n=29,887) between 2013 and 2018. DPP4 inhibitors were chosen as the active comparator as they are used in similar clinical circumstances to SGLT2 inhibitors and are thought to have minimal effects on renal outcomes.
The investigators used registry data and death statistics to track serious renal events over an average of 1.7 years. The primary outcome was a composite endpoint of first occurrence of renal replacement therapy, hospital admission for renal events, or death from renal causes.
The results showed SGLT2 inhibitor initiation was associated with a lower risk of serious renal events than DPP4 inhibitor initiation (2.6 events per 1,000 person-years vs 6.2 events per 1,000 person-years), equating to 3.6 fewer events per 1,000 person-years or a 58% lower relative risk of such events.
The treatment difference was primarily driven by lower rates of renal replacement therapy and hospital admission with SGLT2 inhibitor use; no difference was seen in the rates of death from renal causes.
Subgroup analysis showed the apparent renoprotective effect of SGLT2 inhibitors was particularly marked in patients with a history of cardiovascular disease or chronic kidney disease, and seemed to occur independent of improved glycaemic control.
The researchers highlight the measures they took 'to control for a large number of patient characteristics', but they acknowledge that as an observational study, the possibility of unmeasured confounding cannot be ruled out.