Combination therapies of DPP4 inhibitors and GLP1 analogues with insulin in type 2 diabetic patients: a systematic review

Curr Vasc Pharmacol. 2013 Nov;11(6):992-1000. doi: 10.2174/15701611113119990103.

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 HbA1c 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 HbA1c 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.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
  • Drug Therapy, Combination
  • Glucagon-Like Peptide 1 / administration & dosage*
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Insulin / administration & dosage*
  • Randomized Controlled Trials as Topic / methods
  • Randomized Controlled Trials as Topic / trends

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Insulin
  • Glucagon-Like Peptide 1