In 2012, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) published a position statement on the management of hyperglycemia in patients with type 2 diabetes (T2DM).1 In January, 2015, the ADA and EASD issued an update to the original 2012 statement.2 The authors suggest that the current update should be regarded as an “addendum” to the previous statement. They also emphasize that pharmacotherapy should also always be regarded within the broader context of a “comprehensive cardiovascular risk factor reduction program.”

Therapeutic Options: 2012 vs. 2015

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: SGLT2 inhibitors, have been found effective in reducing hemoglobin A1c (HbA1c) by inhibiting SGLT2 in the proximal nephron, thereby reducing glucose reabsorption and increasing urinary glucose excretion.3,4,5 SGLT2 inhibitors may be used at any stage of the diabetes progression because their mechanism is independent of insulin.2 They are associated with modest weight loss and reduction in systolic and diastolic blood pressure.3.6 The authors note several side effects, including the diuretic impact of SGLT2 inhibitors; they recommend caution in prescribing them to the elderly, patients already taking diuretics, and anyone with a tenuous intravascular volume status.2 In those with an estimated GFR (eGFR) of <45–60mL/min/1.74m2, SGLT2 inhibitors are less effective.2

Thiazolidinediones are no longer regarded as carrying the risk of bladder cancer.7,8 However, they can cause weight gain, peripheral edema, increased incidence of heart failure, and increased risk of bone fractures.9,10 More positively, however, pioglitazone is now available in generic form, thereby decreasing its cost.2

Dipeptidyl Peptidase 4 (DPP-4) inhibitors are being studied for potential link with cardiovascular disease and heart failure and until findings are released, this class of medication should be used cautiously, if at all, in patients with a history of heart failure.2 The DPP-4 inhibitors (as well as the glucagon-like peptide 1 receptor agonists [GLP-1 RAs], which are also incretin-based therapies) continue to carry warnings about potential pancreatitis and pancreatic neoplasia; however, emerging data do not show statistically increased rates of pancreatic disease.2