Real-world data back renal benefits with SGLT2 inhibition
medwireNews: Use of sodium-glucose cotransporter (SGLT)2 inhibitors is associated with a reduced risk for renal events in people with type 2 diabetes in clinical practice, say researchers.
The study’s primary outcome was a composite of serious renal events, comprising dialysis or kidney transplant, hospital admission for renal events, and death from renal causes. During follow-up, this occurred at a rate of 2.6 per 1000 person–years among 29,887 new users of SGLT2 inhibitors, compared with 6.2 per 1000 person–years among 29,887 matched new users of dipeptidyl peptidase (DPP)-4 inhibitors, giving a significant 58% reduction in risk.
This comprised significant reductions of 1.7 and 2.9 events per 1000 person–years for dialysis/transplantation and hospital admissions, respectively, and a nonsignificant reduction of 0.1 renal deaths per 1000 person–years, although the number of events was much smaller for this than the other two individual endpoints.
Peter Ueda (Karolinska Institutet, Stockholm, Sweden) and co-researchers used national registry data to identify people who started an SGLT2 inhibitor in Sweden, Denmark, and Norway during 2013–2018. The average follow-up time was 1.4 years, with 66.1% of this accounted for by time using dapagliflozin, followed by empagliflozin (32.6%), and canagliflozin (1.3%).
These people were matched to new users of DPP-4 inhibitors based on 57 variables that influenced the probability of being prescribed an SGLT2 inhibitor versus a DPP-4 inhibitor. Average follow-up was 2.0 years for the DPP-4 inhibitor group, with sitagliptin use accounting for nearly two-thirds of this.
The average age of the cohort was 61.3 years, and 60.7% were men. Most were taking metformin, around a quarter were using insulin, and most were taking multiple medications, with about two-thirds taking angiotensin-converting enzyme inhibitors and lipid-lowering medications. Nearly a third of the cohort had atherosclerotic heart disease or heart failure at baseline, but only 3.3% had chronic kidney disease.
The renoprotective effect of SGLT2 inhibitors was consistent in men and women and across younger and older age categories. It persisted irrespective of whether people had major cardiovascular disease or chronic kidney disease at baseline, although the effect size was larger in people with these comorbidities.
The findings are published in The BMJ, with an editorial from Steven Smith (University of Florida, Gainesville, USA), who says that “although SGLT2 inhibitors appeared particularly beneficial in people with cardiovascular disease or chronic kidney disease, it is perhaps more informative that these drugs were associated with a lower risk of development and progression of diabetic kidney disease in patients without these overt comorbidities, who have largely been excluded from clinical trials.”
However, he highlights the potential for unmeasured confounders in real-world studies, and calls for “[a]dditional pragmatic comparative effectiveness trials in real world settings and more diverse populations,” which he suggests “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.”
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