Comparative cardiovascular risks of dipeptidyl peptidase 4 inhibitors with other second- and third-line antidiabetic drugs in patients with type 2 diabetes

Aims: Dipeptidyl peptidase 4 inhibitors (DPP4is) are suggested as a second- and third-line antidiabetic treatment for type 2 diabetes. Previous studies assessed only the cardiovascular effects of DPP4is as a second-line treatment, included sulphonylurea as the only comparator, and yielded inconclusive results on the risk of heart failure. The present study therefore evaluated the comparative cardiovascular risks of DPP4is with other second- and third-line antidiabetic drugs. Methods: Based on a large nationwide diabetic cohort, 113 051 patients with type 2 diabetes newly on metformin-based dual or triple therapy were identified in 2009–2011 and followed until 2013, or death if this occurred sooner. Primary interest targeted hospitalizations for ischaemic stroke, myocardial infarction and heart failure. Secondary outcomes were hypoglycaemia and all-cause mortality. Cox proportional hazards models were performed to assess time-to-event hazard ratio between propensity score-matched antidiabetic treatment groups. Results: DPP4is as a second-line add-on to metformin had a significantly lower stroke risk [hazard ratio (HR) 0.817 (95% confidence interval 0.687, 0.971)] and all-cause mortality [HR 0.825 (0.687, 0.992)] than those for sulphonylurea. DPP4is as a third-line add-on to metformin and sulphonylurea combined dual therapy had a significantly lower risk for stroke [HR 0.826 (0.740, 0.923)] and all-cause mortality [HR 0.784 (0.701, 0.878)] than those for acarbose, and significantly lower risks for stroke [HR 0.653 (0.542, 0.786)], heart failure [HR 0.721 (0.568, 0.917)] and all-cause mortality [HR 0.689 (0.594, 0.703)] than those for meglitinide. Conclusions: DPP4is as a second- or third-line add-on treatment provided cardiovascular benefits and posed no increased risks for heart failure, hypoglycaemia or death.