Ninety percent of patients with diabetes will require a multi-drug regimen within 10 years of starting treatment, according to a presentation made at Internal Medicine 2011, the annual meeting of the American College of Physicians in San Diego. Since diabetic progression is almost inevitable, the question becomes which drug to use and when. To help, Anne Peters, MD, FACP, CDE, director of the clinical diabetes programs at the University of Southern California, spoke on "Pharmacotherapy Practices in Type 2 Diabetes," offering a review of key pharmacologic therapies. Treat diabetes early and aggressively, she urged. Keep in mind that patients with new-onset diabetes are frightened, which makes them motivated, Dr. Peters said. There's approximately a three-month window to enact lifestyle changes and instill good habits that can have as much of an effect as drug therapies. Metformin is the first-line treatment, she notes. It's well known, inexpensive, and has the best profile whether the goal is lowering A1c (by 1% to 2%) or avoiding weight gain or hypoglycemia, Dr. Peters said. Its maximal clinical effect is at 1,500 to 2,000 mg/d. Sulfonylureas are the most common second-line agent. They're inexpensive, but have a limited window of use and limited durability as they can affect beta-cell function, she said. While this drug class creates a 1% to 2% drop in A1c in the first year, there follows a rise that steadily increases in years two through 10. Thiazolidinediones are a class that Dr. Peters uses in patients who show markers of insulin resistance such as dyslipidemia, central obesity, or established cardiovascular disease (for which the agents have some benefit). The class has a durable span of effect; Dr. Peters has patients who've used them for 15 years. However, Increased weight gain, edema, and heart failure are risks. GLP-1 agonists work on excess food intake by promoting satiety and reducing appetite. They will enhance glucose-dependent insulin secretion and beta-cell functional mass, regulate gastric emptying, and lower postprandial glucagon secretion after eating. DPP-4 enhances the effects of GLP-1 agonists, according to Dr. Peters. It can achieve an A1c reduction of 0.5% to 0.8%, with a limited side effect profile, no weight change, and no hypoglycemia. She prefers it for use in the elderly, where patients are more fragile. Finally, Dr. Peters addressed the issue of intensive glycemic control, which has become controversial and recently prompted updated guidelines cautioning against it. According to her, lowering A1C to < 7% significantly reduces the risk of microvascular complications in both type 1 and type 2 diabetes, but does not reduce the risk of CVD events in short term studies or significantly increase mortality risk across studies. Further, intensive therapies can triple rates of severe hypoglycemia and cause risk of significant weight gain.