Pathophysiologic Approach to Therapy in Patients With Newly Diagnosed Type 2 Diabetes

Two general approaches to the treatment of type 2 diabetes mellitus (T2DM) have been advocated. 1 ) A “guideline” approach that advocates sequential addition of antidiabetes agents with “more established use” (1); this approach more appropriately should be called the “treat to failure” approach, and deficiencies with this approach have been discussed (2). And 2 ) a “pathophysiologic” approach using initial combination therapy with agents known to correct established pathophysiologic defects in T2DM (3). Within the pathophysiologic approach, choice of antidiabetes agents should take into account the patient’s general health status and associated medical disorders. This individualized approach, which we refer to as the ABCD(E) of diabetes treatment (4), has been incorporated into the updated American Diabetes Association (ADA) guidelines (5). Even though physicians must be cognizant of these associated conditions (ABCDE) when initiating therapy in newly diagnosed T2DM patients, we believe that the most important consideration is to select antidiabetes agents that correct specific pathophysiologic disturbances present in T2DM and that have complementary mechanisms of action. Although it has been argued that the pathogenesis of T2DM differs in different ethnic groups (6), evidence to support this is weak. Although the relative contributions of β-cell failure and insulin resistance to development of glucose intolerance may differ in different ethnic groups (6), the core defects of insulin resistance in muscle/liver/adipocytes and progressive β-cell failure (3) are present in virtually all T2DM patients and must be treated aggressively to prevent the relentless rise in HbA1c that is characteristic of T2DM. In subsequent sections, we provide a review of the natural history of T2DM, specific pathophysiologic abnormalities responsible for T2DM, currently …