I hear that there are seven different types of pills for diabetes now. Is there a preferred order in which to try them and can they all be combined?

I hear that there are seven different types of pills for diabetes now. Is there a preferred order in which to try them and can they all be combined?

The various types of medications for diabetes are illustrated in Table 4 . While there is no right or wrong order in which to try them, there are certain important principles that guide the use of diabetic medications. Important examples of these principles are effectiveness, safety, avoidance of weight gain, avoidance of low blood sugar, avoidance of side effects, long-lasting effectiveness, smallest number of pills required per day, lowest cost, and lack of interaction with other medications being taken by the patient.

The overriding principle is that treatment must be tailored to the specific needs of each individual patient. Thus, while no medication can be said to be right for every patient, there is almost always a medication or combination of medications that can be used in each individual patient. Decision making is further complicated by the cost structure of your medical insurance company’s drug formulary. Thus, while a certain pill may be more or less desirable from a medical perspective, the cost may factor significantly into the decision as to whether to use it and this can differ among various insurance plans.

Although many and complex factors must be taken into consideration, certain generally accepted patterns of practice have evolved among those caring for people with diabetes. Metformin is often the drug of first choice because it is inexpensive, does not cause weight gain (it may cause a modest weight loss), and does not cause low blood sugar.

However, it has certain side effects and cannot be used in patients who have various medical problems, such as liver and kidney disease or some forms of serious lung and heart problems. After metformin, the sulfonylureas are often used frequently, even though they can cause both low blood sugar and weight gain. However, they are generally very inexpensive. If this were not the case, sulfonylureas would probably be used much less often than they are and will probably be less and less used as the cost of safer alternative pills comes down over time. The newer class of pills known as DPP-IV inhibitors (e.g., sitagliptin) is very safe, convenient, and fairly effective, and does not cause weight gain or low blood sugar, but is more costly.

The thiazolidinediones (TZDs or glitazones) are effective and do not cause low blood sugar, but they can be associated with weight gain and fluid retention and should not be used in people with, or at high risk for, heart failure. They are also expensive. The latter two types of pills therefore remain second line when cost is an issue. Other types of pills such as the meglitinides and the alpha-glucosidase inhibitors have their place in the management of diabetes, but are also usually not first-line drugs. Table 6 shows an example of a common order in which diabetes pills can be used when considerations of cost are set aside.

These classes of pills can be used in most combinations. Not all of these combinations are specifically approved by the Food and Drug Administration, but many are. The only classes of medication that have been specifically shown to be no more effective when combined together than when used alone are the sulfonylureas and the meglitinides, since they both work through a similar mechanism to release insulin, although they activate it in different ways.

Table 6 Example of an Order in Which Oral Antidiabetic Drugs Can Be Tried

Medication	Choice	Reasons(s)
Metformin	1st	Potent, no weight gain, no hypoglycemia, inexpensive
DPP-IV-I	2nd	Mid-potent, no weight gain, no hypoglycemia, very few side effects, can be used with liver or kidney disease
Pioglitazone	3rd	Potent, durable effect, no hypoglycemia, cholesterol benefits, heart protective
Meglitinides	4th	Potent, rapid effect, less hypoglycemia
Sulfonylureas	5th	Potent, rapid effect, inexpensive
Acarbose	6th	No hypoglycemia, no weight gain
Colesevelam	7th	No hypoglycemia, no weight gain, cholesterol benefits

Note: 
This table does not take into account potential reasons why one or other drugs may not be suitable for a given patient. Treatment decisions must be tailored to the needs and for the safety of the patient. This is an example only.