Metformin combined with dipeptidyl peptidase-4 inhibitors or metformin combined with sulfonylureas in patients with type 2 diabetes: A real world analysis of the South Korean national cohort

Aims: We explored the risks associated with metformin plus sulfonylurea (MET + SU) or MET plus a dipeptidyl peptidase-4 inhibitor (MET + DPP4i) for hypoglycemia, cardiovascular disease (CVD) events and all-cause mortality in type 2 diabetes (T2D) patients with comorbidities. Methods: This retrospective cohort study is based on the South Korean National Health Insurance Service National Sample Cohort, enrolling T2D patients with one or more diabetes-related comorbidities who switched from monotherapy to MET + SU or MET + DPP4i between July 1, 2008 and December 31, 2013. The risk of hypoglycemia, CVD events and all-cause mortality was examined using Cox's proportional hazard modeling and propensity score matching. Results: Overall, 5693 patients with a mean of 2.6 comorbidities in addition to diabetes were included. Compared with MET + SU, MET + DPP4i treatment was associated with a lower risk of hypoglycemia, CVD events and all cause mortality; adjusted HRs (95% CI), 0.39 (0.18-0.83), 0.72 (0.54-0.97), and 0.64 (0.39-1.05), respectively. Propensity score matching showed comparable results. In further subgroup analyses according to comorbidity type and number, MET + DPP4i was associated with less CVD events and all-cause mortality compared to MET + SU. This increased with more complex comorbid status. Conclusions: In T2D patients with comorbidities, MET + DPP4i treatment is associated with lower risks of CVD events and all-cause mortality compared with MET + SU, independent of type or number of comorbidities. A more complex comorbid status further increases this effect (C) 2018 Elsevier Inc. All rights reserved.