The Significance of Administering Gliflozins in Real Practice in Diabetics Without CV and Renal Disease
Current care standards recommend the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i, i.e., gliflozins) regardless of glycemic compensation in patients with type 2 diabetes (T2DM) and kidney disease, heart failure, or high cardiovascular (CV) risk. A recent study published in the Clinical Journal of the American Society of Nephrology (CJASN) assessed whether long-term use of SGLT2i brings benefits compared to dipeptidyl peptidase-4 inhibitors (DPP4i, i.e., gliptins) in diabetics without documented CV or renal disease using data from a large Israeli database.
Study Methodology
Patients with type 2 diabetes who initiated treatment with gliflozins (empagliflozin or dapagliflozin) or DPP4i (sitagliptin, linagliptin, vildagliptin, saxagliptin) available in Israel between 2015 and 2021 were matched based on propensity score (1:1) using 90 parameters. The renal composite parameter included a confirmed reduction of at least 40% in estimated glomerular filtration rate (eGFR) or kidney failure. The "kidney-or-death" indicator additionally included all-cause mortality. The decline in eGFR was also compared. The authors analyzed the overall population and a subgroup of diabetics without documented cardiovascular and renal disease at study entry.
A total of 19,648 patients were included, of which 53% (10,467) had low cardiorenal risk. The median follow-up period was 38 months.
Findings
The renal composite parameter occurred with a frequency of 6.9 vs. 9.5 events per 1,000 patient-years for SGLT2i vs. DPP4i, and the kidney-or-death parameter at 17.7 vs. 22.1 events per 1,000 patient-years. The initiation of SGLT2i was associated with a significant reduction in the risk of the renal composite parameter (hazard ratio [HR] 0.72; 95% CI 0.61–0.86; p < 0.001) and the kidney-or-death parameter (HR 0.80; 95% CI 0.71–0.89; p < 0.001) compared to DPP4i. In patients without cardiovascular or renal disease, the initiation of SGLT2i compared to DPP4i led to a lower risk of the kidney-or-death parameter (HR 0.77; 95% CI 0.61–0.97), while the risk reduction of the renal composite parameter showed only a statistically insignificant trend (HR 0.67; 95% CI 0.44–1.02).
SGLT2i treatment also slowed the eGFR decline compared to DPP4i in both the overall diabetic population (by 0.49 ml/min/1.73 m2/year) and in diabetics without cardiovascular or renal disease (by 0.48 ml/min/1.73 m2/year).
Conclusion
In a study involving nearly 20,000 patients with T2DM, long-term use of SGLT2i compared to DPP4i in real-world practice was associated with a slower decline in eGFR and a reduced risk of the composite parameter, which includes significant deterioration of renal function (≥ 40% decline in eGFR/kidney failure) or all-cause mortality, in both the overall population and in diabetics without cardiovascular or renal disease at study entry.
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Source: Melzer-Cohen C., Schechter M., Rozenberg A. et al. Long-term, real-world, kidney function changes with SGLT2i versus DPP4i type 2 diabetes without cardiovascular or kidney disease. CJASN 2023 Sep 1; 18 (9): 1153−1162, doi: 10.2215/CJN.0000000000000218.
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