Renal outcomes and all‐cause death associated with sodium‐glucose co‐transporter‐2 inhibitors versus other glucose‐lowering drugs (CVD‐REAL 3 Korea)

Abstract

Aims To investigate the effectiveness of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors on the risk of progression to end‐stage renal disease (ESRD) and all‐cause mortality in a broad range of patients with type 2 diabetes (T2D) using a Korean nationwide cohort. Materials and Methods Using data from the Korean National Health Insurance Service database from January 2014 to December 2017, a total of 701 674 patients were identified with T2D. We divided these patients into new users of SGLT2 inhibitors and new users of other glucose‐lowering drugs (oGLDs). Using propensity scores, patients in the two groups were matched 1:1. We assessed the risk of ESRD and all‐cause death. Results There were 45 016 patients in each group, and baseline characteristics were well balanced between the groups. The patients' mean age was 58.1 ± 10.6 years and mean estimated glomerular filtration rate (eGFR) was 89.2 ± 27.4 mL/min/1.73m2, and 8% of patients had proteinuria. We identified 167 incident ESRD cases and 1070 all‐cause deaths during follow‐up. Use of SGLT2 inhibitors versus oGLDs was associated with a lower risk of ESRD (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.34 to 0.65) and all‐cause death (HR 0.82, 95% CI 0.73 to 0.93). In a subgroup analysis by eGFR, initiation of SGLT2 inhibitor treatment, compared with oGLD treatment, was associated with lower risk of progression to ESRD among patients with eGFR 60 to 90 mL/min/1.73m2 and those with eGFR < 60 mL/min/1.73m2, and a lower risk of all‐cause death was associated with SGLT2 inhibitors versus oGLDs in patients with eGFR ≥90 and 60 to 90 mL/min/1.73m2. Conclusion In this large nationwide study of Korean patients with T2D, initiation of SGLT2 inhibitors versus oGLDs was associated with lower risk of ESRD and all‐cause death.

Sodium-glucose cotransporter inhibitors may reduce the risk of pneumonia: an updated meta-analysis of cardiovascular outcome trials

“…Possible pathophysiological explanations that might account for the observed reduction in the risk of pneumonia include activation of M2 macrophages, inhibition of lipid raft formation, increased production of ketone bodies, prevention of cytosolic pH reduction and induced shift of energy metabolism towards an increased reliance on lipid oxidation [ 11 – 13 ]. The reasons for the differential association of SGLT2i with the risk of pneumonia versus upper or lower respiratory infection are unknown [ 2 ].…”

“…The present meta-analysis confirms that treatment with SGLTi is associated with a lower risk of pneumonia compared with placebo in patients at high cardiometabolic risk. In this context, ongoing RCTs (DARE-19 and TACTIC-E) will elucidate the efficacy and safety of SGLTi on the progression, complications and mortality associated with COVID-19 [ 11 , 19 ]. Considering their cardiovascular benefit, SGLTi should not be interrupted during current pandemic.…”

The effect of sodium‐glucose transport protein 2 inhibitors on mortality and heart failure in randomized trials versus observational studies

“…We searched PubMed on November 4, 2020, and identified 23 observational studies assessing the effect of SGLT‐2 inhibitors on all‐cause mortality, cardiovascular mortality, or heart failure 13,16,18,25‐45 as shown in Table 1. The flow and selection of studies is available in the PRISMA diagram in Data .…”

“…Twelve studies compared the effect of SGLT‐2 inhibitors with DPP‐4 inhibitors, 17,26,27,31,32,37‐39,43‐45 six studies compared the effect of SGLT‐2 inhibitors versus oGLD, 13,16,18,29,33,41 one study compared the effect of SGLT‐2 inhibitors versus GLP‐1 receptor agonists, 40 and one study compared patients exposed to SGLT‐2 inhibitors versus unexposed 25 . These studies included between 14,000 and 603,685 participants and the follow‐up period for intention‐to‐treat analysis was between 5 and 36 months.…”

SGLT2-Inhibitoren: Was gibt es Neues?

“…Eine Analyse von skandinavischen Krankenkassendaten konnte ebenfalls eine niedrigere Inzidenz von terminaler Niereninsuffizienz und Hospitalisierung aufgrund von Nierenerkrankungen bei mit SLGT2i behandelten T2DM-Patienten im Vergleich zu DPP4i feststellen [ 19 ]. Eine Analyse von Krankenkassendaten aus Korea im Rahmen der CVD-REAL-3-Studie kommt zu ähnlichen Ergebnissen: Hier zeigte sich bei mit SGLT2i behandelten Diabetespatienten ein niedrigeres Risiko für eine terminale Niereninsuffizienz (HR: 0,47; 95 %-KI: 0,34–0,65) im Vergleich zu gematchten Kontrollpatienten [ 20 ].…”