The epidemic of T2DM encompasses a spectrum of pathophysiological derangements that require a focused and individualized therapeutic approach. When considering medication choices, the American Diabetes Association (ADA) guidelines suggest inclusion of the duration of disease, age, body weight, life expectancy, expense and variations in microvascular and macrovascular complications. Therapy is usually initiated with metformin which is well known to decrease hepatic gluconeogenesis and effectively lower hemoglobin A1c (HbA1c). This drug is usually chosen as first line as it is well tolerated, has comparable efficacy, an attractive generic price and low rate of toxicity. Over time, progressive deterioration of beta cell function and insulin resistance usually require add-on therapies. Options are sulfonlyureas, dipeptidyl peptidase-4 (DPP4) inhibitors and thiazoladinediones (TZDs). However, as Bennett et al recently evaluated in a meta-analysis, most therapies have similar effectiveness in reduction of HbA1c by 1 percent, but each class has different side effects.