When lifestyle changes, such as diet and exercise, are not enough, patients with type 2 diabetes often take one or more drugs to control their disease. Patients and physicians are faced with a dizzying array of no fewer than 11 different classes of diabetes medications. Recently, researchers conducted a major evidence-based review to determine which drug classes are most effective in treating type 2 diabetes, and if combination therapy confers additional benefits. They found that the older diabetes drug metformin is just as good, if not better, than newer classes of medications. In addition, any two-drug combination produces similar diabetes control, but they have different adverse events.
The researchers identified published studies that reported on major long-term clinical outcomes for approved diabetes medications. They looked at medication effects on control of hemoglobin A1c (blood sugar) levels, body weight, and lipid levels, as well as various side effects, such as hypoglycemia (excessively low blood sugar level). In addition to metformin, second-generation sulfonylureas, thiazolidinediones, meglitinides, DPP-4 inhibitors, and glucagon-like peptide-1 receptor agonists were included in the studies examined. A total of 166 articles were selected for review.
Overall, most of the diabetes medications used alone in the reviewed studies decreased HbA1c by about 1 percentage point. Similar results were obtained with various two-drug combinations. Metformin performed better than several other classes by not increasing body weight and by lowering LDL-cholesterol. There was also a better safety profile with metformin in terms of risk for low blood sugar. For example, sulfonylureas had a fourfold higher risk for mild or moderate hypoglycemia compared with metformin. This risk increased to fivefold when these types of drugs were used in combination with metformin compared with other combinations. Increased risks for congestive heart failure and bone fractures were observed for thiazolidinediones.
More research is needed to evaluate long-term clinical outcomes, such as cardiovascular and kidney disease, of these various classes of diabetes drugs, particularly in older patients and those with other conditions who may be at increased risk for adverse events.
The study was supported by the Agency for Healthcare Research and Quality (Contract No. 290-02-0018). See "Comparative effectiveness and safety of medications for type 2 diabetes: An update including new drugs and 2-drug combinations," by Wendy L. Bennett, M.D., M.P.H., Nisa M. Maruthur, M.D., M.H.S., Sonal Singh, M.D., M.P.H., and others in the May 3, 2011, Annals of Internal Medicine 154(9), pp. 602-613.