Dapagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in people with type 2 diabetes (CVD-REAL Nordic) when compared with dipeptidyl peptidase-4 inhibitor therapy: a multinational observational study

AIMS: To compare the sodium glucose-cotransporter-2-inhibitor (SGLT-2i) dapagliflozin versus dipeptidyl peptidase-4 inhibitors (DPP-4i) regarding risk associations of MACE (nonfatal myocardial infarction, nonfatal stroke or cardiovascular [CV] mortality), hospital events for heart failure (HHF), atrial fibrillation, and severe hypoglycemia for type 2 diabetes (T2D) patients in a real-world setting.

METHODS: All T2D patients dispensed with glucose lowering drugs (GLDs) during 2012-2015 were identified in nationwide registries in Denmark, Norway and Sweden. Patients were divided in two groups; new users of dapagliflozin and new users of DPP-4i, matched 1:3 by propensity score, calculated by patient characteristics, co-morbidities and drug treatment. Cox survival models estimated hazard ratio per country separately; a weighted average was calculated.

RESULTS: After matching, a total of 40,908 T2D patients were identified as new users of dapagliflozin (n=10,227) or DPP-4i (n=30,681). The groups were well balanced at baseline; mean-age was 61 years and 23% had CV disease. Mean follow-up time was 0.95 years, with a total of 38,760 patient-years. Dapagliflozin was associated with lower risk of MACE, HHF and all-cause mortality compared to DPP-4i; hazard ratios (HRs): 0.79 (95% CI 0.67-0.94), 0.62 (0.50-0.77), and 0.44 (0.33-0.60), respectively. Numerically lower, but non-significant HRs were observed for myocardial infarction (0.91 [0.72-1.16]), stroke (0.79 [0.61-1.03]) and CV mortality (0.76 [0.53-1.08]) Atrial fibrillation and severe hypoglycemia showed neutral associations.

CONCLUSIONS: Dapagliflozin was associated with lower risks of cardiovascular events and all-cause mortality compared to DPP-4i in a in a real-world clinical setting and broad T2D population.