A comparison of agents used to manage type 2 diabetes mellitus: need for reappraisal of traditional approaches.

In patients with type 2 diabetes mellitus, the traditional method of initiating therapy with a sulfonylurea and increasing the dosage until maximum levels are reached before adding an insulin-sensitizing agent has persisted and should be re-evaluated. Similarly, the current practice of starting therapy with one agent and increasing to maximum dosage before adding a second agent, rather than starting with combination therapy, also needs to be addressed. There is much evidence to suggest that initiating therapy with lower doses of two agents that have complementary effects can increase the overall efficacy and decrease the incidence of adverse effects. Clearly, there is a need for a paradigm shift away from the traditional approach of therapy using insulin secretagogues to a more pathophysiologic approach using an insulin-sensitizing agent, such as the thiazolidinediones. The thiazolidinediones have been shown to reduce insulin resistance, improve the ability of beta-cells to produce insulin, and decrease cardiac risk factors. By reducing insulin resistance, improving glycemic control, and preserving beta-cell function with a thiazolidinedione early in the course of therapy, it is likely that durable glycemic control will be achieved and both microvascular and macrovascular complications may be reduced. Furthermore, early use of an insulin-sensitizing agent either alone or incombination is expected to improve both acute and long-term outcomes in patients with type 2 diabetes.