- Kenny Lin, MD, MPH
When comparing therapies for type 2 diabetes, physicians, patients, and quality measures often get caught up in the disease-oriented outcome of glycemic control. However, a 2014 editorial in AFP pointed out that of the medications then available to lower blood sugar levels, only metformin reduced mortality and clinically relevant complications. Since that time, studies of newer diabetes medications have demonstrated mortality benefits in patients with cardiovascular disease. However, the best second-line medication after metformin remains unclear. Although the World Health Organization guideline recommended inexpensive sulfonylureas as second-line therapy in low-resource settings, the American College of Physicians and the American Academy of Family Physicians suggested "the choice of drug [after metformin] should be based on a conversation with the patient about benefits, possible harms, and cost."
In the February 15 issue of AFP, Drs. Joshua Steinberg and Lyndsay Carlson applied the STEPS criteria (safety, tolerability, effectiveness, prince, and simplicity) to each of the 10 categories of diabetes medications (including insulin). Their analysis confirmed that metformin should be first-line pharmacotherapy for most persons with type 2 diabetes. Other key points from this article include:
Safety - Sulfonylureas, insulins, meglitinides, and pramlintide increase risk of hypoglycemia. Metformin and acarbose require monitoring, dose adjustments, or discontinuation in patients with chronic kidney disease.
Tolerability - Side effects across different drug classes range from gastrointestinal effects (metformin, acarbose, meglintinides, pramlintide, GLP-1 receptor agonists, SGLT-2 inhibitors) to weight gain (sulfonylureas), edema (TZDs), severe arthralgias (DPP-4 inhibitors), and genital and urinary tract infections (SGLT-2 inhibitors).
Effectiveness - Recent trials showed improved patient-oriented outcomes from some GLP-1 receptor agonists and SGLT-2 inhibitors in patients at high cardiovascular risk or with known cardiovascular disease. Acarbose also reduces cardiovascular events.
Price - Metformin, acarbose, sulfonylureas, and generic pioglitazone are the most affordable options.
Simplicity - Acarbose and meglitinides are taken three times daily before meals, while insulins, GLP-1 receptor agonists, and pramlintide require subcutaneous injections.