Currently Available Diabetes Drugs   (December 18, 2011))

Someone recently asked for the names of the currently available FDA approved prescription medications for treating type 2 diabetes.

As of December 2011, there are eleven classes of medications approved by the FDA for lowering blood sugar in type 2 diabetes.  Many of the approved medications have two names: a brand name and a generic name. Most of these classes have multiple drugs that act based on the same mechanism. It's hard to keep up with all the names, as sometimes one active ingredient is sold under several brand names by the same company depending on the country it's being marketed in, and because variants of the active ingredient might have different names depending on duration of activity or manufacturer.

Additionally, there are now several medications that include two classes of diabetes drugs in the same tablet; I won't go into detail on these combinations, as they are proliferating as manufacturers try to increase sales by combining two proven drugs into one tablet. And, unsurprisingly, there are variations on presently-approved drugs in development (frequently sarcastically referred to as "me-too" drugs), and of course there are other classes of medications that are presently undergoing study, and may be approved by the FDA at some time in the future.

1. The oldest class, and still considered a good one for many people, are the sulfonylureas. These drugs include Amaryl (glimepiride), DiaBeta, Glynase PresTab, and Micronase (all of which share the active ingredient glyburide), Glucotrol and Glucotrol XL (glipizide), and older drugs such as Diabinese (chlorpropamide), tolazamide and tolbutamide. These drugs all work to release insulin from the beta cells, and they all have a risk of hypoglycemia.

2. Metformin is the only available drug in the biguanide class of diabetes drugs. It is sold under names such as Glucophage, Glucophage XR, and Riomet. Metformin is frequently considered the first medication to be used when drug treatment of T2DM is needed. It does not cause hypoglycemia, but has a rare potentially-fatal side effect called lactic acidosis that means it should not be used if the patient has kidney disease or will be having surgery or X-rays using injections of contrast material. There was a biguanide drug called phenformin which was previously available, but it was withdrawn many years ago because of higher potential of lactic acidosis.

3. The thiazolidinediones (also called "TZDs" or "glitazones") include two drugs at present: Actos (pioglitazone) and Avandia (rosiglitazone). Both drugs decrease insulin resistance - they help sensitize the body's tissues to insulin effects, and neither causes hypoglycemia. But both have problems: Actos is associated with a risk of bladder cancer, and Avandia has  been associated with an increased risk of cardiovascular events, such as heart attacks and strokes. There was a third TZD drug called Rezulin (troglitzaone) previously available, but it was withdrawn because of an increased risk of liver failure.

4. A recently-developed class of oral diabetes drugs are the dipeptidyl peptidase-4 inhibitors ("DPP-4 inhibitors"). There are now three DPP-4 inhibitors that have been approved in the US: Januvia (sitagliptin), Onglyza (saxagliptin), and Tradjenta (linagliptin). A fourth, Galvus (vildagliptin), has been approved in Europe and elsewhere, but was not approved in the United States.

5. Another class, called incretin mimetics, need to be given by injection. Byetta (exenatide) and Victoza (liraglutide) are approved; a once-weekly version of Byetta, called Bydureon, has received marketing authorization in the European Union and is currently under review by the FDA.

6. Insulin. There are numerous varieties, and different ways to categorize them: I think the most useful is based on duration of action. A helpful table describing the different insulins is available from the National Diabetes Information Clearinghouse.

In addition, there are several classes of marginally-effective diabetes drugs have been developed and approved for treatment of T2DM, but haven't been widely used because of lack of efficacy and/or frequent side effects:

7. These include the alpha-glucosidase inhibitors, Glyset (miglitol) and Precose (acarbose), which work by slowing the digestion of starchy foods. They cause flatulence and bloating frequently.

8. The meglitinides, Prandin (repaglinide) and Starlix (nateglinide) work similarly to the sulfonylureas, but have a very short duration of action, and also can cause hypoglycemia.

9. Cycloset (bromocriptine) is an older drug used for Parkinson's disease and for some pituitary tumors that also has some effectiveness in lowering blood sugar in T2DM. It can cause low blood pressure, fainting, and may worsen psychotic disorders.

10. Symlin (pramlintide) is an injectable medication that works for both T1DM and T2DM, but must be given with insulin. It can cause severe hypoglycemia unless the insulin dose is carefully adjusted.

11. Welchol (colesevelam) is in a class of medications called bile acid sequestrants. It was originally approved for use to lower cholesterol, and was found to lower blood sugar in T2DM when used with other diabetes drugs

Finally, for completeness, I'll mention some classes of diabetes drugs that might be approved in the future:

A compound related to aspirin, called salsalate, can lower blood sugar.

Dual-PPAR modulators: several have failed clinical trials, but one, aleglitazar, is apparently still in development.

Several SGLT2 inhibitors, such as dapagliflozin, are being developed; data about dapagliflozin was presented to an FDA Advisory Committee this past summer, and it was recommended that it should not be approved until there is more data in light of safety concerns linking it with breast and bladder cancers and drug-induced liver injury.

Glucokinase Activators (GKAs for short) work by activating an enzyme called glucokinase, which is found in the beta cells of the pancreas; GK seems to be responsible for the rate of glucose metabolism.

I must add one final thought: Wikipedia has webpages on most of the diabetes drugs, and most have tabulations at the bottom showing the various classes of drugs -- but the reader must be warned: the listings are incomplete.