Efficacy and safety of dipeptidyl peptidase-4 inhibitors as an add-on to insulin treatment in patients with Type 2 diabetes: a review

AIM: To review and discuss the results from the clinical controlled trials comparing a dipeptidyl peptidase-4 inhibitor with placebo treatment as add-on to insulin treatment with respect to changes in HbA1c , weight, fasting plasma glucose, risk of hypoglycaemia and safety in patients with Type 2 diabetes.

METHODS: We searched the MEDLINE and PubMed databases to identify all randomized controlled clinical trials evaluating dipeptidyl peptidase-4 inhibitors as an add-on to insulin in patients with Type 2 diabetes, which were selected for review. The abstracts and posters of the recent annual meetings of the American Diabetes Association and European Association for the Study of Diabetes were hand searched, as were the reference lists of articles identified.

RESULTS: Adding a dipeptidyl peptidase-4 inhibitor to insulin treatment resulted in a glucose-lowering effect of ~ 6.6-8.7 mmol/mol (0.60-0.80%) from a baseline HbA1c of 67-78 mmol/mol (8.3-9.3%), without increasing the risk of hypoglycaemia. The dipeptidyl peptidase-4 inhibitor treatment had no effect on body weight or daily dose of insulin. The frequency and severity of adverse events did not differ between dipeptidyl peptidase-4 inhibitor and placebo treatment.

CONCLUSION: Adding a dipeptidyl peptidase-4 inhibitor treatment to insulin has a moderate effect on HbA1c , a weight-neutral effect and a good safety profile. The risk of hypoglycaemia is not increased despite a significant improvement in HbA1c .