A rational approach to drug therapy of type 2 diabetes mellitus

Several new pharmacological agents have recently been developed to optimise the management of type 2 (non-insulin-dependent) diabetes mellitus. The ai m of this article is to briefly review the various therapeutic agents avail able for management of patients with type 2 diabetes mellitus and to sugges t a potential approach to drug selection. There are three general therapeut ic modalities relevant to diabetes care. The first modality is lifestyle ad justments aimed at improving endogenous insulin sensitivity or insulin effe ct. This can be achieved by increased physical activity and bodyweight redu ction with diet and behavioural modification, and the use of pharmacologica l agents or surgery. This first modality is not discussed in depth in this article. The second modality involves increasing insulin availability by th e administration of exogenous insulin, insulin analogues, sulphonylureas an d the new insulin secretagogue, repaglinide. The most frequently encountere d adverse effect of these agents is hypoglycaemia. Bodyweight gain can also be a concern, especially in patients who are obese. The association betwee n hyperinsulinaemia and premature atherosclerosis is still a debatable ques tion. The third modality consists of agents such as biguanides and thiazoli dinediones which enhance insulin sensitivity, or agents that decrease insul in requirements like the alpha-glucosidase inhibitors. Type 2 diabetes mellitus is a heterogeneous disease with multiple underlyin g pathophysiological processes. Therapy should be individualised based on t he degree of hyperglycaemia, hyperinsulinaemia or insulin deficiency. In ad dition, several factors have to be considered when prescribing a specific t herapeutic agent. These factors include efficacy, safety, affordability and ease of administration.