Clinical Translation of “A Diabetes Outcome Progression Trial”:ADOPTAppropriate Combination Oral Therapies in Type 2 Diabetes

The long-term goals for the management of type 2 diabetes mellitus (T2DM) center on the prevention of its chronic micro- and macrovascular complications, which requires normalization of glycemia and control of cardiovascular risk factors (1). Growing evidence from large clinical trials supporting earlier and more aggressive therapeutic strategies to manage hyperglycemia in diabetes has been reflected in current guidelines and practice recommendations (2–5). Recent clinical trials on controlling hyperglycemia have supported more efficacious therapeutic approaches, most of which have clearly shown that double or triple combinations of available and emerging pharmaceutical agents are required to achieve that elusive, but well-recognized, near-normal hemoglobin A1c goal of less than 6.5% (6). T2DM results from a combination of physiological abnormalities including systemic insulin resistance coupled with inadequate β-cell insulin secretion (7). The etiology of these defects is not fully understood. Classic studies from the United Kingdom Prospective Diabetes Study (UKPDS) revealed that hyperglycemia in T2DM tends to be progressive due to persistent insulin resistance with gradual worsening of β-cell insulin secretory function (8). For the majority of patients, it is well-known that maximizing doses of single oral medications does not provide a sustained normalization of glycemia and can provoke unwanted side effects (9). Moreover, diabetes results from a complex interplay among several pathophysiological mechanisms, and it seems doubtful that in the near future a therapeutic “magic bullet” will be identified to effectively “cure” the hyperglycemia of diabetes (7). Thus, successful current therapeutic approaches use early adoption of oral combination therapies, among the variety of medications that (thankfully) are currently available for use.