Combination Therapies of DPP4 Inhibitors and GLP1 Analogues with Insulin in Type 2 Diabetic Patients: A Systematic Review

Evangelos   C.   Rizos; Evangelia   E.   Ntzani; Nikolaos      Papanas; Vasilis      Tsimihodimos; Zoi      Mitrogianni; Efstratios      Maltezos; Moses   S.   Elisaf

Abstract

Objective: The use of dipeptidyl-peptidase 4 (DPP4) inhibitors and glucagon like peptide 1 (GLP1) analogues for the treatment of diabetic mellitus (DM) type 2 is growing. Currently some of these agents have been approved in combination with insulin. Methods: We considered randomised controlled trials (RCTs) evaluating GLP1 analogues or DDP4 inhibitors combined with basal insulin in diabetic patients. We were limited to trials published in English language. Results: PubMed search retrieved 207 items. After excluding irrelevant items we ended with 7 eligible studies with 1808 participants. Mean baseline HbA_1c was 8.5% and median follow up was 24 weeks. Exenatide combined with insulin was used in 2 studies; DPP4 inhibitors were used in 5 studies (2 with sitagliptin, 1 with saxagliptin, 1 with vildagliptin and 1 with alogliptin). Conclusion: Incretin-based therapies combined with basal insulin are able to reduce HbA_1c by 0.5-0.7%. DPP4 inhibitors have no significant effect on weight, whereas GLP1 analogues reduced weight by 1-2 kg. Hypoglycaemia rates were generally comparable in all treatment groups. These are promising results, but the available evidence is limited. This is a poorly investigated field with few RCTs. New studies focusing on head-to-head comparisons with short-acting insulin on top of basal insulin are needed.

Keywords: Exenatide, liraglutide, sitagliptin, saxagliptin, vildagliptin, alogliptin, insulin, diabetes mellitus.