Numerous oral medications (pills) are available for the treatment of type 2 diabetes mellitus, each with its own set of advantages and disadvantages. There are currently seven classes of oral medications to treat diabetes, with each class having a unique mechanism of action to help control diabetes.
- Sulfonylureas (2nd Generation)
- Glipizide (Glucotrol®)
- Glimepiride (Amaryl®)
- Glyburide (DiaBeta®, Micronase®, and Glynase®)
- Biguanides
- Metformin (Glucophage®, Fortamat®, Riomet®, and Glumetza®)
- Thiazolidinediones (TZD’s)
- Pioglitazone (Actos®)
- Rosiglatizine (Avandia®)
- Meglitinides
- Repaglinide (Prandin®)
- Nateglinide (Starlix®)
- Alpha Glucosidase Inhibitors
- Acarbose (Precose®)
- Miglitol (Glyset®)
- Dipeptidyl Peptidase-4 Inhibitors (DPP-4 Inhibitors)
- Sitagliptin (Januvia®)
- Bile Acid-binding Molecule
- Colesevelam (WelChol®)
Sulfonylureas (SU’s) have been available for decades and the older first generation medications should really not be used anymore so I will limit my discussion to the second generation medications. The SU’s treat type 2 diabetes by causing the pancreas’s insulin producing beta cells to make more insulin and thus lower glucoses. They can produce good glucose reductions however this is not a sustained reduction in that over time the pancreas makes less and less insulin and this diminished insulin production can be accelerated with the use of SU’s. Hypoglycemia (low blood glucose) is a common side effect of SU therapy. I avoid the use of SU’s, if at all possible, in my practice due to the hypoglycemia and due to the fact that SU’s do not treat the underlying cause of type 2 diabetes, insulin resistance, but instead overload the system with extra insulin to overcome this insulin resistance.
There is only one Biguanide on the market, Metformin; however, it is available from a number of manufacturers and is available in immediate release and extended release versions. The most common side effect of Metformin is gastrointestinal (GI) in nature with nausea & diarrhea being the most common complaints that I will hear from my patients. The extended release version is much less likely to have these GI side effects; therefore, I avoid the immediate release version. Metformin is typically the first line of treatment for all people with type 2 diabetes unless they have a contraindication to its use including renal insufficiency or congestive heart failure. One of the causes of elevated glucoses in type 2 diabetes is the fact that the liver produces too much glucose and Metformin is an excellent product that decreases the liver’s production of glucose thus improving diabetes control.
TZD’s target the insulin resistance that is type 2 diabetes by improving the skeletal muscle’s and fat cell’s sensitivity to insulin. The most common side effects are swelling and weight gain but these can be avoided with strict salt restriction and calorie reduction. TZD’s should not be used in people with uncontrolled heart failure. TZD’s may help to preserve the function of the pancreas’s beta cells and thus may slow the progressive nature of type 2 diabetes. These are excellent products and I frequently use them in my practice due to the good glucose control and the fact that they may protect beta cells.
Meglitinides are similar to SU’s in that they cause the pancreas to release insulin; however, they are shorter acting than SU’s and are given immediately before a meal to control after eating glucoses that rise in response to food. Therefore, the disadvantages are that they need to be taken 2 or 3 times a day with each meal and they can induce hypoglycemia. I use these only when someone has a specific problem with after eating glucose elevations that have not responded to other medications.
Alpha Glucosidase Inhibitors work in the gut by blocking the absorption of carbohydrates into the blood stream and therefore are best used to treat elevated after eating glucoses. The main disadvantages are the need for dosing 2 or 3 times daily before each meal and gastrointestinal (GI) side effects such as flatulence, diarrhea, and abdominal pain. These GI side effects make dosing and tolerance very difficult and I therefore rarely use this class of medications.
Dipeptidyl Peptidase-4 Inhibitors (DPP-4 Inhibitors) are relatively new to the market and work by raising a chemical in the body called Glucagon-like Peptide-1 (GLP-1). GLP-1 is released from cells in the intestine in response to food in the gut. GLP-1 causes the pancreas to release insulin but only if glucoses become elevated and thus do NOT cause hypoglycemia. There is at the present time only one DPP-4 Inhibitor on the market but numerous other will be available soon. They are very well tolerated and the only common side effect is “cost” in that they are not available as generic medications. They may have beta cell preserving properties that could make them even more attractive for use it this is proven to be the case. They are once daily medications and have modest glucose reductions.
There is a Bile Acid-binding Molecule, Colesevelam (WelChol®), that was initially approved for the treatment of elevated cholesterol. It was found to also have modest glucose lowering properties by binding carbohydrates in the gut and Colesevelam was then approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes. The main side effect, as with the Alpha Glucosidase Inhibitors, is gastrointestinal, mainly constipation and dyspepsia. The only other problems are “cost” and pill size and number. A treatment dose is 3 “large” pills twice a day before breakfast and supper.
The art of medicine is how the prescribe these numerous different medications to best control glucoses and thus prevent long-term diabetes complications. Strive for good control without side effects such as hypoglycemia.