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

Objective: 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.

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.