DPP-4 inhibition and islet function

Abstract

During recent years, dipeptidyl peptidase-4 (DPP-4) inhibition has been included in the clinical management of type 2 diabetes, both as monotherapy and as add-on to several other therapies. DPP-4 inhibition prevents the inactivation of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). This results in stimulation of insulin secretion and inhibition of glucagon secretion, and there is also a potential β-cell preservation effect, as judged from rodent studies; that is, it might target the key islet dysfunction in the disease. In type 2 diabetes. This reduces 24-h glucose levels and reduces HbA1c by ≈ 0.8-1.1% from baseline levels of 7.7-8.5%. DPP-4 inhibition is safe, with a very low risk for adverse events including hypoglycemia, and it prevents weight gain. The present review summarizes the studies on the influence of DPP-4 inhibition on islet function. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00184.x, 2012).

Keywords: Dipeptidyl peptidase‐4 inhibition; Glucagon secretion; Insulin secretion.

Figure 1

Glucose, glucagon‐like peptide‐1 (GLP‐1), insulin and glucagon levels in patients with type 2 diabetes after meal ingestion after 4 weeks of treatment with vildagliptin or placebo. Means ± SEM are shown. Adapted from reference 44 with permission from The Endocrine Society.

Figure 2

Glucagon response to (a) meal ingestion or (b) hypoglycemia induced by lowering glucose levels to 2.6 mmol/L in patients with type 2 diabetes after 4 weeks of treatment of with vildagliptin or placebo. Means ± SEM are shown. Asterisks show the probability level of random difference between the groups; *P < 0.05, **P < 0.01. Adapted from reference 58 with permission from The Endocrine Society.