Cardiovascular and mortality benefits of sodium–glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus: CVD-Real Catalonia

Abstract

Background Evidence from prospective cardiovascular (CV) outcome trials in type 2 diabetes (T2DM) patients supports the use of sodium–glucose co-transporter-2 inhibitors (SGLT2i) to reduce the risk of CV events. In this study, we compared the risk of several CV outcomes between new users of SGLT2i and other glucose-lowering drugs (oGLDs) in Catalonia, Spain. Methods CVD-REAL Catalonia was a retrospective cohort study using real-world data routinely collected between 2013 and 2016. The cohorts of new users of SGLT2i and oGLDs were matched by propensity score on a 1:1 ratio. We compared the incidence rates and hazard ratio (HR) for all-cause death, hospitalization for heart failure, chronic kidney disease, and modified major adverse CV event (MACE; all-cause mortality, myocardial infarction, or stroke). Results After propensity score matching, 12,917 new users were included in each group. About 27% of users had a previous history of CV disease. In the SGLT2i group, the exposure time was 60% for dapagliflozin, 26% for empagliflozin and 14% for canagliflozin. The use of SGLT2i was associated with a lower risk of heart failure (HR: 0.59; 95% confidence interval [CI] 0.47–0.74; p < 0.001), all-cause death (HR = 0.41; 95% CI 0.31–0.54; p < 0.001), all-cause death or heart failure (HR = 0.55; 95% CI 0.47–0.63; p < 0.001), modified MACE (HR = 0.62; 95% CI 0.52–0.74; p < 0.001), and chronic kidney disease (HR = 0.66; 95% CI 0.54–0.80; p < 0.001). Conclusions In this large, retrospective observational study of patients with T2DM from a Catalonia, initiation of SGLT-2i was associated with lower risk of mortality, as well as heart failure and CKD.

The Impact of Novel Anti-Diabetic Medications on CV Outcomes: A New Therapeutic Horizon for Diabetic and Non-Diabetic Cardiac Patients

“…When comparing the cardiovascular effect of SGLT2i with DDP-4 inhibitors [ 41 ] or sulfonylureas derivates [ 42 ] in real world data, SGLT2i have demonstrated superior reduction in all-cause mortality, while other outcomes were inconclusive. Further real-world observational studies have strengthened these findings [ 43 , 44 , 45 , 46 ]. To date, several SGLT2i have been approved: Empagliflozin, Canagliflozin, Dapagliflozin, and Sotagliflozin, which is a combined SGLT1 and SGLT2 inhibitor ( Table 1 and Table 2 ).…”

Anti-inflammatory role of SGLT2 inhibitors as part of their anti-atherosclerotic activity: Data from basic science and clinical trials

“…Similarly, the CANOSSA trial, a prospective and open-label study that enrolled 35 patients with diabetes mellitus and stable chronic heart, demonstrated that the canagliflozin administration (100 mg/day for 12 months) induced a significant decrease in hs-CRP after 3, 6, and 12 months compared with baseline (3 months: p = 0.002, 6 months: p = 0.001, 12 months: p = 0.007) ( 68 ).…”

The Place and Value of Sodium-Glucose Cotransporter 2 Inhibitors in the Evolving Treatment Paradigm for Type 2 Diabetes Mellitus: A Narrative Review

“…In addition, SGLT2i use was associated with improved cardiorenal outcomes and reduced all-cause mortality, compared with DPP-4is [ 81 ]. Real-world data from the CVD-REAL Catalonia study (including 25,834 people with T2DM) demonstrated that SGLT2i use was associated with a lower risk of HF, all-cause mortality, modified MACE (all-cause mortality, myocardial infarction or stroke) and CKD compared with other glucose-lowering treatments ( P < 0.001 for each outcome) [ 84 ].…”