Normalization of Blood Glucose Prior to Starting on GLP-1 Improves Outcome

Near-normalization of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes.

In individuals with type 2 diabetes, there is considerable evidence that prolonged exposure of beta-cells to high glucose levels or glucotoxicity induces functional defects in insulin secretion in response to secretagogues.

Glucotoxicity is known to be partly reversible. On these grounds it was hypothesized that improved glycemic control might enhance the potentiating effect of glucagon-like peptide (GLP-1). It was investigated whether 4 weeks of intensive insulin treatment, designed to bring blood glucose in patients with type 2 diabetes to near-normal, would improve the ability of GLP-1 to enhance glucose-induced insulin secretion. It was shown that near-normalization of blood glucose significantly improves beta-cell sensitivity to glucose during infusion of glucose plus GLP-1, suggesting that impaired action of GLP-1 in patients with type 2 diabetes may be secondary to lack of metabolic control.

This raises the possibility that GLP-1 treatment may gradually improve hyperglycaemia during treatment with other antihyperglycaemic agents such as dipeptidyl-dipeptidase inhibitors.

Højberg PV, Zander M, Vilsbøll T, Knop FK, Krarup T, Vølund A, et al. Near normalisation of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes. Diabetologia. 2008;51:632-40.