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

Aims To evaluate the efficacy and safety of combining insulin therapy with dipeptidyl peptidase 4 (DPP-4) inhibitors compared to combining insulin therapy with placebo or other antihyperglycaemic agents. Materials and Methods A literature search was conducted via electronic databases. The inclusion criteria were randomized controlled trials (RCTs) comparing the addition of DPP-4 inhibitors to insulin with the addition of placebo or other active hypoglycaemic agents to insulin therapy, study duration of no less than 12 weeks performed in type 2 diabetes patients, and the availability of outcome data to evaluate a change in the HbA1c. Results The HbA1c-lowering efficacy was significantly greater with DPP-4 inhibitor/insulin (DPP-4i/INS) than with placebo/insulin (PBO/INS) [weighted mean difference (WMD) -0.54% (95% CI -0.62, -0.45), P<0.01]. The fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) lowering efficacies were also significantly greater with DPP-4i/INS than with PBO/INS [WMD -0.40 mmol/L (95% CI -0.79, -0.02) and -1.83 mmol/L (95% CI -2.43, -1.24), P<0.05]. The risk of hypoglycaemia or severe hypoglycaemia was similar for DPP4i/INS and PBO/INS treatments. There was no significant difference in the glycaemia lowering efficacy between DPP-4i/INS and metformin/insulin (MET/INS), alpha glucosidase inhibitors/insulin (AGI/INS), sulfonylurea/insulin (SU/INS), thiazolidinedione/insulin (TZD/INS), and glucagon-like peptide-1 receptor agonist/insulin (GLP-1RA/INS). Sodium glucose cotransporter-2 inhibitor/insulin (SGLT-2i/INS) treatment achieved better placebo-corrected efficacy in lowering FPG and PPG with less weight gain and no higher risk of hypoglycaemia. Conclusions Treatment with DPP-4 inhibitors combined with insulin improved glycaemic control without an increased risk of hypoglycaemia or weight gain compared with insulin treatment alone. This article is protected by copyright. All rights reserved.