American Diabetes Association Complete Guide to Diabetes: The Ultimate Home Reference from the Diabetes Experts


Medications for Type 2 Diabetes

• Review of Type 2 Diabetes

• Classes of Diabetes Pills

• Injectable Medications

• Choosing a Medication

• General Precautions

Some people with type 2 diabetes manage their blood glucose with changes to their diet and physical activity. However, many other people need medications, such as pills or insulin, to keep their blood glucose in the target range. There are also new injectable medications for people with type 2 diabetes. Insulin is discussed in detail in the next chapter.

This chapter will outline the basic classes of medications, uses, and warnings and precautions. You will work closely with your health care team to determine which medication is best for you. Keep in mind that the specific medication you and your health care provider choose is less important than making sure you meet your target blood glucose in a safe and effective manner. Medications change, and your needs change too, so remember to discuss any problems or concerns with your provider.

There are six classes of diabetes pills and two classes of injectable medications (not including insulin). Each drug class targets a specific problem in type 2 diabetes. Let’s review the blood glucose problems that can occur in type 2 diabetes.

Review of Type 2 Diabetes

In type 2 diabetes, a number of problems can occur with both insulin resistance and insulin sensitivity. Remember, in type 1 diabetes, people eventually don’t make any insulin. In type 2 diabetes, people usually make some insulin. However, people with type 2 diabetes may not make enough insulin, may become resistant to insulin, or a combination of both.

Type 2 Diabetes Basics

• Your body, including your muscle and liver, develops insulin resistance.

• Your pancreas doesn’t make enough insulin to overcome this insulin resistance.

• Blood glucose stays in the blood because muscles cells won’t take in glucose properly.

• Also, the liver releases glucose inappropriately.

Classes of Diabetes Pills

There are several classes of diabetes pills on the market, as well as combination pills. Some are sold under generic and brand names, and others are only sold under brand names. Each class of drug has its own target in the body, as well as its advantages and disadvantages.

Classes of Diabetes Pills

• Alpha-glucosidase inhibitors

• Biguanides (metformin)

• DPP-4 inhibitors

• Meglitinides

• Sulfonylureas

• Thiazolidinediones (TZDs)

• Combination pills

Alpha-Glucosidase Inhibitors

Alpha-glucosidase inhibitors include the medications acarbose and miglitol. Alpha-glucosidase inhibitors have been on the market for over a decade—acarbose first became available in 1996. Alpha

-glucosidase inhibitors lower blood glucose by slowing the digestion of carbohydrates after meals. People take them with the first bite of each meal.

Advantages of Alpha-Glucosidase Inhibitors

• Do not tend to cause weight gain.

• Do not usually cause low blood glucose when used alone. When used in combination with another medication, glucose is required to treat low blood glucose, if it should occur.

• Can be effective in people recently diagnosed with diabetes who have trouble with post-meal blood glucose levels.

• Can be used in combination with other pills or insulin.

Side Effects and Precautions for Alpha-Glucosidase Inhibitors

• Gas, bloating, and diarrhea.

• Should not be taken if you have inflammatory bowel disease, other intestinal diseases, or obstructions.

• Can cause low blood glucose when used in combination with other medications and insulin.

• Talk to your doctor for a full list of side effects and cautions.

Biguanides (Metformin)

Biguanides include only one medication—metformin. In addition to regular metformin, there is extended-release metformin and liquid metformin. Metformin has been on the market since 1994. Metformin lowers blood glucose by putting a brake on the liver’s release of stored glucose. Metformin may also lower insulin resistance in the muscles. It is usually taken twice a day, although extended-release metformin is taken once a day.

Advantages of Metformin

• Risk of hypoglycemia is low.

• Can sometimes lower high blood lipid levels and promote weight loss.

• Can be used along with other classes of pills or insulin. Because they work in different ways, metformin and sulfonylureas are often prescribed together.

Side Effects and Precautions for Metformin

• Common, initial side effects include diarrhea, loss of appetite, and nausea. These usually subside over time.

• Lactic acidosis is a rare, but serious side effect.

• You should not take metformin if you have kidney failure or advanced heart failure, liver disease, or low oxygen from respiratory problems. You should stop taking metformin if you are in the hospital or going to have iodinated contrast X-rays.

• If you binge drink, take certain heart medications, or are 80 years of age or older, metformin may not be right for you.

• Talk to your doctor for a full list of side effects and cautions.

• People using metformin for long periods can have difficulty absorbing vitamin B2 and should have their levels checked regularly.

DPP-4 Inhibitors

DPP-4 inhibitors currently include sitagliptin and saxagliptin. The FDA approved sitagliptin in 2006. DPP-4 inhibitors increase insulin secretion and decrease the liver’s release of glucose. They do this by preventing the breakdown of a compound called the glucagon-like peptide-1 (GLP-1). DPP-4 inhibitors are taken once a day.

Advantages of DPP-4 Inhibitors

• Do not usually cause low blood glucose when used without insulin or insulin secretagogues, medications that stimulate the beta-cells in the pancreas to release insulin.

• Do not tend to cause weight gain.

• Tend to have a neutral or positive effect on cholesterol levels.

Side Effects and Precautions for DPP-4 Inhibitors

• Occasional stomach discomfort and diarrhea.

• People with kidney problems may need to take lower doses.

• Acute pancreas problems have been reported with sitagliptin. The FDA continues to monitor these cases.

• Talk to your doctor for a full list of side effects and cautions.


Meglitinides include the medications repaglinide and nateglinide. They lower blood glucose by stimulating the pancreas to release insulin. They may be helpful for people who have problems with high blood glucose immediately after a meal. Meglitinides are taken before each of the three meals.

Advantages of Meglitinides

• Do not cause weight gain.

• When compared to sulfonylureas, meglitinides may reduce the risk of hypoglycemia between meals and at night.

• Can be used with metformin.

Side Effects and Precautions for Meglitinides

• Can cause low blood glucose.

• People with liver problems should not take meglitinides.

• Talk to your doctor for a full list of side effects and cautions.


Different sulfonylureas are prescribed in the United States. Some are available as brand names as well as the following generic name medications: glyburide, glipizide, extended-release glipizide, and glimepiride.

Sulfonylureas lower blood glucose levels by stimulating the pancreas to produce and release more insulin. Sulfonylureas have been used since the 1950s. The effects of sulfonylurea drugs on blood glucose levels were discovered by accident in the 1940s (they were used as antibacterial drugs during World War II). Generally, people take sulfonylureas once or twice a day before meals.

Advantages, Precautions, and Side Effects of Sulfonylureas

Sulfonylureas can cause low blood glucose. You should not take a sulfonylurea if you are pregnant or planning a pregnancy or if you have significant heart, liver, or kidney disease. Each sulfonylurea has different side effects and precautions. Talk to your doctor about the risks and benefits of using specific sulfonylureas.

Thiazolidinediones (TZDs)

Thiazolidinediones include pioglitazone and rosiglitazone. The FDA approved them in 1999, although the first TZD, called Rezulin, was taken off the market because it caused liver problems. TZDs lower blood glucose by lowering insulin resistance in the muscles and liver. They also reduce the liver’s production of glucose. They are taken once or twice a day.

Advantages of TZDs

• If you also take insulin, you may be able to reduce your insulin dose.

• May lower triglyceride levels and increase HDL cholesterol levels.

Precautions and Side Effects for TZDs

• Can cause weight gain and fluid retention.

• Both pioglitazone and rosiglitazone have been shown to increase the risk of heart failure. Rosiglitazone (brand name Avandia) may increase the risk of heart attacks and death.

• May increase the risk of bone loss and fractures.

• Talk to your doctor for a full list of side effects and cautions.

Rosiglitazone (Avandia) and Increased Risks of Heart Attacks

In 2007, the U.S. Food and Drug Administration (FDA) began examining rosiglitazone because research studies indicated that use of the drug might increase the risk of heart attacks and other heart-related conditions, potentially leading to death.

  After reviewing the risks, the FDA restricted the use and prescription of rosiglitazone in 2010. Patients already taking rosiglitazone may continue taking the drug if they acknowledge that they are aware of the cardiovascular risks associated with it and if it is working for them. New patients will only be prescribed rosiglitazone if no other treatments have been effective in managing their diabetes. In these cases, the patient’s doctor must document and prove that his or her patient would be best served by taking the drug. Further, patients must review safety information that describes the risks that come with taking rosiglitazone.

  If you currently take rosiglitazone, consult with your doctor immediately about what you should do. Do not stop taking the medication on your own; uncontrolled blood glucose carries its own risks as well.

Combination Pills

There are several combination pills available to people with type 2 diabetes. These can be more effective than a single medication and more convenient than taking three or four pills. Most combination pills combine metformin with other medications. Talk to your doctor about the advantages, disadvantages, and side effects of combination pills.

Combination Pills

• Metformin and glyburide

• Metformin and rosiglitazone

• Metformin and glipizide

• Metformin and pioglitazone

• Metformin and sitagliptin

• Metformin and repaglinide

• Pioglitazone and glimepiride

• Rosiglitazone and glimepiride

Injectable Medications

In addition to pills, people with type 2 diabetes now have the option of taking injectable medications to lower their blood glucose. There are two classes of injectable medications: glucagon-like peptide-1 agonists (GLP-1 agonists) and amylin agonists.

GLP-1 Agonists

There are two GLP-1 agonists, exenatide (brand name Byetta) and liraglutide (brand name Victoza). Exenatide is used with other diabetes medications to lower blood glucose. It is injected with a pen-like injector. Exenatide received FDA approval in 2005. Liraglutide received FDA approval in 2010. It is injected once daily and prescribed to people with type 2 diabetes. Both GLP-1 agonists work by inducing the pancreas to secrete insulin after meals, suppressing appetite, and slowing emptying of the stomach. Neither drug is insulin.

Advantages of GLP-1 Agonists

• Promotes weight loss by suppressing appetite.

• Can be used with metformin, a sulfonylurea, or a TZD.

Side Effects and Precautions for GLP-1 Agonists

• Some patients taking exenatide have experienced altered kidney function. Your health care provider may monitor you carefully for the development of any kidney problems while taking exenatide.

• During drug testing, the medicine in liraglutide caused rats and mice to develop tumors of the thyroid gland. It is currently not known if liraglutide will cause thyroid tumors or a type of thyroid cancer in people.

• Can cause low blood glucose when taken with sulfonylureas.

• Nausea, vomiting, diarrhea, dizziness, and headaches are common side effects but decrease over time.

• Rare but serious pancreas problems can occur, so talk to your doctor.

• Talk to your doctor for a full list of side effects and cautions.

Amylin Agonists

Pramlintide acetate is an amylin agonist. It is an injectable medication for people with type 2 diabetes (or type 1 diabetes) who already use insulin. In general, the medication suppresses appetite and lowers blood glucose after meals. Pramlintide acetate cannot be mixed with insulin and is available in a separate, prefilled pen or vial and syringe.

Choosing a Diabetes Medication

All diabetes medications must be prescribed by a health care professional. Your diabetes care provider will ask about your lifestyle, physical condition, insurance coverage, and personal preferences before prescribing any particular drug or combination of drugs.

Not everyone with type 2 diabetes will be helped by oral or injectable diabetes medications. Oral medications are more likely to lower blood glucose levels in people who have had diabetes for less than 10 years, who are following a healthy meal plan, and who have some insulin secretion by their pancreas. Some drugs are less effective in people who are very thin.

You may order your prescriptions from your local retail pharmacy. Or mail-ordering your medication may appeal to you. Mail order is convenient, and it could save you money. Often, when you receive your prescriptions by mail order, you pay less for a 90-day supply of the medication.

Diabetes Medications and Hospitalization

During severe infections, surgery, or hospitalizations, you may need to replace your oral diabetes medications with insulin injections, at least temporarily.

Tips for Mail-Ordering Medications

• When you start a new drug, first buy it from your local pharmacy. You may need to change the dose or type—or you may stop taking it altogether.

• Don’t buy large quantities of a drug until you find the safe, effective dose for you. This is especially true if the medication is new for you.

• Buy drugs you need right away or for only a short period of time from the pharmacy. Use mail-order firms to buy drugs you use regularly.

• Ask about generic drugs. Savings offered by mail-order firms come routinely from substituting generics for brand-name drugs.

• Inspect your prescription drugs carefully when they arrive. If they look different, call your supplier to double check. Get the name of the manufacturer for your records.

• Always follow instructions when taking prescription drugs. If the instructions that arrive with your medications are different from those you remember, call your provider and ask which instructions to follow.

• Check the expiration date on each item that arrives. If you’ll need the item in 6 months, make sure it doesn’t expire in 2 months. Send back all items with expiration dates that are just around the corner.

• Check out other mail order and shopping tips for all your diabetes supplies in chapter 7.

General Precautions

All sulfonylurea drugs and, to a lesser extent, meglitinides, increase the risk of hypoglycemia, especially if you skip meals or drink too much alcohol. Be sure to talk to your provider about the symptoms to watch for and any precautions you need to take while on your oral medication. Teach your family and friends the warning signs of hypoglycemia. Together, make a plan of action for dealing with unexpected lows.

Oral agents can have other side effects. If you notice any changes in your behavior or your body after starting a course of oral diabetes medications, be sure to tell your provider. If you have side effects, be sure to call your provider and do not just stop taking your medication.

Drugs in Combination

Your health care provider will know which diabetes medications are safe to use in combination. Keep in mind that clinical trials are required in order to receive FDA approval for drugs to be used in combination. The list of approved drug combinations changes, so ask your doctor if you have any questions.

Drug Interactions

Tell your providers and your pharmacist about all your medications—prescription and over-the-counter. This includes vitamins and herbal products.

Sometimes, drugs that are safe by themselves can interact with each other to cause sickness or conditions that can be difficult to diagnose. Some drugs can lower or raise blood glucose levels. This must be accounted for so that your blood glucose levels don’t go too low or stay too high. What looks likes hypoglycemia may really be caused by a drug interaction and can be mistreated.

Many drugs interfere with the way the body uses and eliminates oral diabetes medications. These drugs can indirectly cause high or low glucose levels.

Possible Drug Interactions to Discuss

• Are there any medicines you take when you are coming down with a cold? In bed with the flu?

• Any medications you take when getting a sudden headache?

• Do you take aspirin or thyroid, high blood pressure, or high cholesterol medicines?

In Conclusion

You may find that your blood glucose levels are consistently in the normal range after taking a diabetes medication for a while. That’s great news!

Some people may be able to take a lower-dose medication if they have low blood glucose levels on a regular basis while taking the medication. Ask your health care team whether they suggest that you start a trial of taking a lower dose of your pills. During this trial period, keep monitoring your blood glucose and stay in close contact with your health care team.

There is a possibility that diabetes pills won’t help you at all. Or they may help, but only for a while. Sulfonylureas stop working for 5–10% of people within a year. Eventually, they stop working for another 50% of people. If oral medications no longer help you reach your target blood glucose levels, adding insulin or other injectable medications to your diabetes care plan is usually the next step.

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