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

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.