Eleven classes of diabetes drugs

Way back in 1995, doctors in the US and patients with diabetes had a new option to treat type 2 diabetes: a drug of a different kind from those already available: up until then, the only available drugs for T2DM in the US were the insulins, and a class of drugs called the sulfonylureas. The new drug was in a class called biguanides, and was called metformin; it was initially available only as the brand-name version Glucophage. It's now available generically, and in varying forms, including a liquid and a long-acting version. Interestingly, there had been an earlier drug in the biguanide class (phenformin) which was withdrawn from sale because of a high risk of a complication called lactic acidosis. As a result, the FDA was very leery of approving metformin, even though it was sold in Europe and many other countries for years before it was approved in the States.

But I digress. Metformin was a different class of agents to treat diabetes than those that were then available, and had an entirely different mechanism of action than the other drugs. As such, patients could be treated with various combinations of insulin, sulfonylureas, and metformin, and were able to obtain better glycemic control than before. One thing that was learned over and over was that better control required using drugs from the 3 different classes -- that is, adding a second sulfonylurea to a patient already on maximal doses of another sulfonylurea was unlikely to have any additional effect to lower blood sugar, as the two sulfonylureas would have the same mechanism of action, and hence, it was a waste of time and money to try adding the second. But adding metformin to a program for a patient on a sulfonylurea (or vice versa) was very likely to have great additional benefit. So treatment programs were devised to add a second drug from another class (note, not switch to the other class) when diabetes needed additional treatment, and then to add a third (insulin was the other class that could be used).

Another class of diabetes drugs became available soon after, in 1996: alpha-glucosidase inhibitors, when the FDA approved a drug called acarbose (brand name Precose in the US, and Glucobay elsewhere). Soon after, another was approved, miglitol (AKA Glyset). These drugs work in the intestine, slowing down the digestion of carbohydrates, and lengthening the time it takes for carbohydrates to convert to glucose, thereby facilitating better blood glucose control, but mainly influence the level of blood sugar after eating. These drugs never became popular, partially because they has minimal glucose-lowering effects, and partially because they need to be taken several times daily.

Then in 1997, another new class of diabetes drugs was approved: the thiazolidinediones, also called TZDs or "glitazones." The first agent in this class, troglitazone (brand name Rezulin), again revised physician thinking about treating diabetes: now, with a new and efficacious oral agent, insulin became a last resort for treating T2DM, as doctors used varying combinations of sulfonylureas, metformin, and troglitazone (and sometimes the alpha-glucosidase inhibitors) with considerable success. Competitors in Rezulin's class soon appeared, rosiglitazone (Avandia) and pioglitazone (Actos), and Rezulin was withdrawn from the market after it became clear that it had a risk of toxic effects on the liver.