AIMS: To estimate risks of diabetic ketoacidosis (DKA), acute liver injury (ALI), acute kidney injury (AKI), chronic kidney disease (CKD), severe complications of urinary tract infection (UTI), and genital infection (GI) among patients with type 2 diabetes (T2D) initiating empagliflozin versus those initiating a dipeptidyl peptidase-4 (DPP-4) inhibitor.
MATERIALS AND METHODS: In this large multinational, observational, new-user cohort study in UK, Danish, and US healthcare data sources, patients initiated empagliflozin or a DPP-4 inhibitor between August 2014-August 2019, were aged ≥18 years, and had ≥12 months’ continuous health plan enrolment. Incidence rates by exposure and incidence rate ratios (IRR), adjusted for propensity-score deciles, were calculated.
RESULTS: 64,599 empagliflozin initiators and 203,315 DPP-4 inhibitor initiators were included. There was an increased risk (pooled adjusted IRR [95% confidence interval]) of DKA (2.19 [1.74-2.76]) and decreased risks of ALI (0.77 [0.50-1.19] in patients without predisposing conditions of liver disease; 0.70 [0.56-0.88] in all patients) and AKI (0.54 [0.41-0.73]). In the UK data, there was an increased risk of GI (males: 4.04 [3.46-4.71]; females: 3.24 [2.81-3.74]) and decreased risks of CKD (0.53 [0.43-0.65]) and severe complications of UTI (0.51 [0.37-0.72]). Results were generally consistent in subgroup and sensitivity analyses.
CONCLUSIONS: Compared with DDP-4 inhibitor use, empagliflozin use was associated with increased risks of DKA and GI and decreased risks of ALI, AKI, CKD, and severe complications of UTI. These associations are consistent with previous studies and known class effects of sodium-glucose cotransporter 2 inhibitors, including renoprotective effects and beneficial effects on alanine aminotransferase levels.
