Addition of dipeptidyl peptidase‐4 inhibitors to insulin treatment in type 2 diabetes patients: A meta‐analysis

AIMS/INTRODUCTION: To evaluate the efficacy and safety of combining insulin therapy with dipeptidyl peptidase‐4 (DPP‐4) inhibitors compared with combining insulin therapy with a placebo or other antihyperglycemic agents. MATERIALS AND METHODS: A literature search was carried out via electronic databases. The inclusion criteria were randomized controlled trials comparing the addition of DPP‐4 inhibitors to insulin with the addition of a placebo or other active hypoglycemic agents to insulin therapy, study duration of no less than 12 weeks carried out in type 2 diabetes patients and the availability of outcome data to evaluate a change in the glycated hemoglobin. RESULTS: The glycated hemoglobin‐lowering efficacy was significantly greater with DPP‐4 inhibitor/insulin (DPP‐4i/INS) than with placebo/insulin (weighted mean difference −0.53%, 95% confidence interval −0.63, −0.43, P < 0.01). The postprandial plasma glucose‐lowering efficacies was also significantly greater with DPP‐4i/INS than with placebo/insulin (weighted mean difference −1.65 mmol/L, 95% CI: −2.34, −0.96, P < 0.05). The risk of hypoglycemia or severe hypoglycemia was similar for DPP4i/INS and placebo/insulin treatments. There was no significant difference in the glycemia‐lowering efficacy between DPP‐4i/INS and alpha‐glucosidase inhibitors/insulin, thiazolidinedione/insulin and glucagon‐like peptide‐1 receptor agonist/insulin. Sodium–glucose cotransporter 2 inhibitor/insulin treatment achieved better placebo‐corrected efficacy in lowering postprandial plasma glucose, with less weight gain and no higher risk of hypoglycemia. CONCLUSIONS: Treatment with DPP‐4 inhibitors combined with insulin improved glycemic control without an increased risk of hypoglycemia or weight gain compared with insulin treatment alone.