Insulin Secretagogues

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Abstract
Existing oral insulin secretagogues, sulphonylureas, are associated with hyperinsulinaemia, risk of hypoglycaemia and weight gain. Furthermore, they are not able to offer durable glycaemic control in patents with type 2 diabetes and are associated with progressive decline of beta-cell function. New insulin secretagogues offer an exciting opportunity. Repaglinide, the first prandial glucose regulator, now has convincing data that, compared to sulphonylurea use, it has a lower risk of hypoglycaemia. When used in a flexible dosing regime in a large cohort of patients, it is associated with better glycaemic control, a reduction in HbA1c, weight loss and improved quality of life compared to sulphonylureas. Early data shows the possibility of an effective combination with night time isophane insulin with significant falls in HbA1c and lower doses of insulin required. Nateglinide is an amino acid derivative. It again acts directly on the pancreatic beta-cell. Because of its very short duration of action, and the fact that it appears to secrete insulin in a glucose-dependent manner, it appears to secrete insulin in the closest way to that seen in a person without diabetes. Early data, both in monotherapy and in combination with metformin, show that it is an effective agent in terms of lowering HbA1c, has a low risk of hypoglycaemia and potentially less risk of significant weight gain. These characteristics mean that it may be the ideal agent to be used very early in the disease process, or even in subjects with impaired glucose tolerance, in whom early-phase insulin response is already lost. However these concepts, at the present time, are unproven.