Lower cardiorenal risk with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes without cardiovascular and renal diseases: A large multinational observational study.

AIMS: We compared the new use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus dipeptidyl peptidase-4 inhibitor (DPP4i) and the risk of cardiorenal disease, heart failure (HF) or chronic kidney disease (CKD), in patients with type 2 diabetes without a history of prevalent cardiovascular and renal disease, defined as cardiovascular and renal disease (CVRD) free, managed in routine clinical practice. MATERIALS AND METHODS: In this observational cohort study, patients were identified from electronic health records from England, Germany, Japan, Norway, South Korea and Sweden, during 2012-2018. In total, 1 006 577 CVRD-free new users of SGLT2i or DPP4i were propensity score matched 1:1. Unadjusted Cox regression was used to estimate hazard ratios (HRs) for outcomes: cardiorenal disease, HF, CKD, stroke, myocardial infarction (MI), cardiovascular and all-cause mortality. RESULTS: Baseline characteristics were well balanced between the treatment groups (n = 105 130 in each group) with total follow-up of 187 955 patient years. Patients had a mean age of 56 years, 43% were women and they were indexed between 2013 and 2018. The most commonly used agents were dapagliflozin (91.7% of exposure time) and sitagliptin/linagliptin (55.0%), in the SGLT2i and DPP4i, groups, respectively. SGLT2i was associated with lower risk of cardiorenal disease, HF, CKD, all-cause and cardiovascular mortality; HR (95% confidence interval), 0.56 (0.42-0.74), 0.71 (0.59-0.86), 0.44 (0.28-0.69), 0.67 (0.59-0.77), and 0.61 (0.44-0.85), respectively. No differences were observed for stroke [0.87 (0.69-1.09)] and MI [0.94 (0.80-1.11)]. CONCLUSION: In this multinational observational study, SGLT2i was associated with a lower risk of HF and CKD versus DPP4i in patients with type 2 diabetes otherwise free from both cardiovascular and renal disease.