Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and insulin sensitizers

Abstract

In this review we present the agents that are in use in the treatment of type 2 diabetes. Sulfonylureas of the 1st and 2nd generation increase insulin secretion but can induce hyperinsulinemia and sometimes prolonged hypoglycemia. Glimepiride is a new 3rd generation sulfonylurea with some advantages over the other members of this group, such as a lower risk of hypoglycemia, no interaction with cardiovascular KATP-channels and a possibility that it may increase insulin sensitivity. There are also newer insulin secretagogues (such as neteglinide and repaglinide) with a rapid onset of action on the beta-cell, therefore inducing a more physiological profile of insulin secretion during meals. The category of insulin sensitizers includes metformin and thiazolidinediones. Metformin effectively reduces hyperglycemia, hyperlipidemia and macroangiopathy in patients with type 2 diabetes. This agent increases the sensitivity of the liver and peripheral tissues to insulin and, therefore, it could be considered as a drug of choice for the prevention of type 2 diabetes. Thiazolidinediones (rosiglitazone and pioglitazone) increase the sensitivity of the tissues to insulin. This mechanism of action makes them powerful therapeutic tools for the treatment of type 2 diabetes (and possibly other insulin resistant states) either alone or in combination with other oral agents. The category of agents that interfere with the absorption of glucose and lipids includes alpha-glucosidase inhibitors (acarbose and miglitol) and lipase inhibitors (or-listat). alpha-Glucocidase inhibitors improve the time relationship between plasma insulin and glucose increases after a meal. Therefore, these agents may be used in the treatment of patients with type 2 diabetes, either alone at a very early stage of this disease (when insulin secretion is still adequate), or in combination with insulin secretagogues. alpha-Glucosidase inhibition may also prove useful as a supplement to insulin therapy in patients with type 1 diabetes mellitus. The inhibitor of gastrointestinal lipase orlistat may prove a useful adjunct to hypocaloric diets in patients with type 2 diabetes and obesity.