Does SGLT2 Inhibitor Administration Benefit Diabetics with Low Cardiorenal Risk?

Introduction

The cardiorenal protective effect of SGLT2i has been confirmed in patients with type 2 diabetes (T2DM) who have a high risk of heart and renal damage, both by randomized controlled trials and real-world practice studies. However, the authors of the cited paper, published this year in the journal Diabetes, noted that there is a lack of long-term research on the efficacy of gliflozins in T2DM patients with normal renal function and a low risk of developing heart and kidney disease. They decided to fill this gap in the data.

Methodology and Study Progress

The authors used data from a large Israeli database. They identified patients with type 2 diabetes who started treatment with empagliflozin or another SGLT2i between 2015 and 2021 and who had a low initial risk of renal disease according to the KDIGO classification (estimated glomerular filtration rate [eGFR] ≥ 60 ml/min/1.73 m²; urine albumin-to-creatinine ratio [UACR] < 30 mg/g) and had no history of cardiovascular (CV) conditions. These patients were matched by propensity score with the same number of T2DM patients who started treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4i, also known as gliptins) during the same period based on 120 baseline characteristics. All patients were monitored until an event occurred or the study ended. The primary evaluated parameter was a composite endpoint including a persistent decline in eGFR by ≥ 40%, end-stage renal disease (ESRD), and death from any cause.

This approach created 5,195 pairs of patients, with one in each pair taking empagliflozin or another SGLT2i, and the other taking a DPP-4i. Regarding baseline data of the entire cohort, the median age was 60 years, and the median eGFR was 93 ml/min/1.73 m². The median follow-up period was 35.2 months.

Findings

Among patients treated with empagliflozin, there were 172 events included in the composite endpoint during the study period, corresponding to an incidence of 11.0 events per 1,000 patient-years. For those treated with DPP-4i, there were 215 events, equating to an incidence of 13.7 events per 1,000 patient-years (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.65–0.97; p = 0.02). Similar trends were observed for the renal components of the evaluated parameter, i.e., a persistent eGFR decline of at least 40% and the incidence of ESRD.

Results comparing the use of any gliflozin against gliptins were also analyzed. This analysis included 6,477 pairs of patients, with a median follow-up period of 37.6 months. It also demonstrated a lower risk of the primary composite endpoint in the group treated with SGLT2i. The number of events here was 9.9 per 1,000 patient-years compared to 13.0 events per 1,000 patient-years in the DPP-4i group (HR 0.77; 95% CI 0.64–0.92).

Conclusion

This study observed benefits of SGLT2 inhibitor administration on renal function in type 2 diabetics with low cardiorenal risk compared to DPP-4i. The authors concluded that their findings support the use of gliflozins in this group of patients, regardless of glycemic control achieved.

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Source: Schechter M., Melzer Cohen C., Rozenberg A. et al. Favorable kidney outcomes are associated with empagliflozin vs. DPP4i in patients with diabetes and normal kidney function: real-world evidence. Diabetes 2022; 71 (Suppl. 1): 867-P, doi: 10.2337/db22-867-P.