Endocrine Abstracts

GLP-1 is one of the two known incretin hormones (the other one being GIP), which have the ability to stimulate insulin secretion whenever glucose concentrations are above a certain permissive threshold. The incretin effect (greater stimulation of insulin secretory responses with oral as compared to matched intravenous glucose administration) is reduced in patients with type 2 diabetes, thus the question needed to be addressed, whether there is hyposecretion or impaired action of incretin hormones in patients with type 2 diabetes. Initial findings suggested lesser secretion of GLP-1 in patients with type 2 diabetes, however, with multiple studies available that address this question, no consistent deficiency has been found in meta-analyses. GIP has lost most of its insulinotropic activity in patients with type 2 diabetes, probably related to the overall deficiency in β-cells typical for this condition. Some effectiveness of GLP-1 is preserved in type 2 diabetes, although strictly speaking, the effects of GLP-1 in such patients are reduced, if compared to healthy subjects with normal glucose tolerance. Nevertheless, the effects elicited by GLP-1 or other agents interacting with GLP-1 receptors (GLP-1 receptor agonists) are sufficient to elicit clinically meaningful effects, reducing glucose concentrations in hyperglycaemic patients with type 2 diabetes. Because of the nature of the interaction with β-cells in the islet of Langerhans, GLP-1 receptor stimulation does not trigger hypoglycaemia, and therapy with incretin-based glucose-lowering medications is not complicated by hypoglycaemia, even if near-normal glucose concentrations are achieved. In addition, GLP-1 receptor agonists induce weight loss, the extent of which, however, is highly variable. As an injctable treatment, GLP-1 receptor agonists are as effective as simple insulin regimens in terms of reducing HbA1c. GLP-1 receptor agonists can be used in conjunction with insulin. Novel approaches use fixed-dose combinations of basal insulin and a GLP-1 receptor agonist.