Patient information: Diabetes mellitus type 2: Treatment

TYPE 2 DIABETES OVERVIEW

Type 2 diabetes mellitus occurs when the pancreas (an organ in the abdomen) produces insufficient amounts of the hormone insulin and/or the body becomes resistant to normal or even high levels of insulin. This causes high blood sugar (glucose) levels, which can lead to a number of complications if untreated.

People with type 2 diabetes require regular monitoring and ongoing treatment to maintain normal or near-normal blood sugar levels. Treatment includes lifestyle adjustments, self-care measures, and medications, which can minimize the risk of diabetes and cardiovascular (heart-related) complications.

This topic review will discuss the treatment of type 2 diabetes. Topics that discuss other aspects of type 2 diabetes are also available. (See "Patient information: Diabetes mellitus type 2: Overview" and "Patient information: Diabetes mellitus type 2: Insulin treatment" and "Patient information: Type 2 diabetes mellitus and diet" and "Patient information: Self-blood glucose monitoring in diabetes mellitus" and "Patient information: Hypoglycemia (low blood sugar) in diabetes mellitus" and "Patient information: Diabetes mellitus type 2: Alcohol, exercise, and medical care" and "Patient information: Preventing complications in diabetes mellitus".)

TYPE 2 DIABETES TREATMENT GOALS

Blood sugar control — The goal of treatment in type 2 diabetes is to keep blood sugar levels at normal or near-normal levels. Careful control of blood sugars can help prevent the long-term effects of poorly controlled blood sugar (diabetic complications of the eye, kidney, and cardiovascular system).

Home blood sugar testing — In people with type 2 diabetes, home blood sugar testing is often recommended at least once per day, before the first meal of the day (fasting). (See "Patient information: Self-blood glucose monitoring in diabetes mellitus".)

A normal fasting blood sugar is less than 100 mg/dL (5.6 mmol/L), although some people will have a different goal. A healthcare provider can help to determine this goal. Some people will need to test their blood sugar before and/or after other meals during the day, and the frequency of testing can change over time.

A1C testing — Blood sugar control can also be estimated with a blood test called A1C. The A1C blood test measures the average blood sugar level during the past two to three months. The test is done with a small sample of blood from a vein or fingertip in a clinician's office. The goal A1C for most people with type 2 diabetes is 7 percent or less, which corresponds to an average blood sugar of 150 mg/dL (8.3 mmol/L, (table 1). A healthcare provider can determine the optimal A1C goal for you.

The average blood sugar goal (150 mg/dl or 8.3 mmol/L) is higher than the fasting blood sugar goal (100 mg/dL or 5.6 mmol/L) for several reasons. Blood sugar increases after eating. The amount and speed of the increase depend upon the type and amount of food eaten at a particular meal. The increase also depends upon the type and dose of diabetes treatment(s) used and the person's activity level.

Cardiovascular risk control — The most common long-term complication of type 2 diabetes is cardiovascular (heart) disease, which can cause myocardial infarction (heart attack), angina (chest pain), stroke, and even death. The risk of heart disease is estimated to be at least twice that of persons without diabetes.

However, people with type 2 diabetes can substantially lower the risk of cardiovascular disease by quitting smoking, taking a low-dose aspirin every day, and by managing high blood pressure and hyperlipidemia (high cholesterol) with diet, exercise, and medications. A detailed discussion of ways to prevent complications is available separately. (See "Patient information: Preventing complications in diabetes mellitus".)

DIET AND EXERCISE IN TYPE 2 DIABETES

Changes in diet can improve many aspects of type 2 diabetes, including obesity, high blood pressure, and the body's ability to produce and respond to insulin. Detailed information about type 2 diabetes and diet is available separately. (See "Patient information: Type 2 diabetes mellitus and diet".)

Regular exercise can benefit people with type 2 diabetes, even if weight is not lost. Exercise improves blood sugar control because it improves the body's response to insulin. (See "Patient information: Diabetes mellitus type 2: Alcohol, exercise, and medical care".)

TYPE 2 DIABETES MEDICATIONS

A number of oral medications are available for the treatment of type 2 diabetes. A table of these medications is available in table 2 (table 2).

Metformin — Most patients who are newly diagnosed with type 2 diabetes will immediately begin a medication called metformin (Glucophage®, Gumetza®, Riomet®, Fortamet®). Metformin improves the body's response to insulin to reduce high blood sugar levels.

Metformin is a pill that is usually started with a dose of 500 mg with the evening meal; a second dose may be added one to two weeks later (500 mg with breakfast). The dose may be increased every one to two weeks thereafter.

Side effects — Common side effects of metformin include nausea, diarrhea, and gas. These are usually not severe, especially if metformin is taken along with food and the dose is increased gradually.

Patients with certain types of kidney, liver, and heart disease, and those who drink alcohol excessively should not take metformin. It should be stopped 48 hours before any test that uses iodine-based contrast dye, and it should be stopped before surgical procedures. It is not recommended for patients older than 80 years unless kidney function testing shows that the kidneys are functioning well.

When to add a second medication — For people who initially take metformin, a second medication may be added within the first two to three months if blood sugar control is not adequate. "Adequate" control is defined as an A1C level less than 7 percent for most people; insulin is often recommended if the A1C is higher than 8.5 percent. (See "Patient information: Diabetes mellitus type 2: Insulin treatment".)

Which second medication is best? — If blood sugar control is not adequate after two to three months, but the A1C is close to the goal (between 7 and 8.5 percent), a second medication may be added. The "best" second medication depends upon individual factors, including the person's weight, other medical problems, and preferences regarding use of injections. The following are general recommendations:

• The most commonly recommended second medication is a short acting sulfonylurea, such as glipizide (see 'Sulfonylureas' below.
• A thiazolidinedione, such as pioglitazone, is an alternative to sulfonylureas, but only for people who are not at increased risk of heart failure or bone fracture (see 'Thiazolidinediones' below.
• A GLP-agonist, such as exenatide, is an option for patients who are overweight and who want to avoid developing low blood sugar. (See 'GLP-agonists' below.)

• A meglitinide, such as repaglinide, is an option for people who cannot take a sulfonylurea or prefer to avoid injections. (See 'Meglitinides' below.)

Sulfonylureas — Sulfonylureas have been used to treat type 2 diabetes for many years. They work by increasing insulin production, and can lower blood sugar levels by approximately 20 percent. However, they lose effectiveness over time.

Sulfonylureas are generally used if metformin does not adequately control blood sugar levels when taken alone, but may be used first in people who have liver, kidney, or heart disease and in those who drink alcohol excessively. They should not be used by patients who are allergic to sulfa drugs.

A number of sulfonylureas are available (Diabinese®, Orinase®, Glucotrol®, Diabeta®, Micronase®, Glynase®, Amaryl®), and the choice between them depends mainly upon cost and availability; their efficacy is similar. The medication is in pill form and is taken once or twice daily.

Patients who take sulfonylureas are at risk of low blood sugar, known as hypoglycemia. This can cause sweating, shaking, hunger, and anxiety, and must be treated quickly by eating 10 to 15 grams of fast-acting carbohydrate (eg, fruit juice, hard candy, glucose tablets). It is possible to lose consciousness (pass out) if treatment is delayed. A full discussion of low blood sugar is available separately. (See "Patient information: Hypoglycemia (low blood sugar) in diabetes mellitus".)

Insulin — In the past, insulin treatment was reserved for patients with type 2 diabetes whose blood sugars were not controlled with oral medications and lifestyle changes. However, there is increasing evidence that using insulin at earlier stages may improve overall diabetes control and help to preserve the pancreas's ability to make insulin.

Insulin injections may be used as a first-line treatment in some people with type 2 diabetes, or it can be added to or substituted for oral medications. Insulin must be injected by the patient or a family member/friend. (See "Patient information: Diabetes mellitus type 2: Insulin treatment".)

Thiazolidinediones — This class of medications includes rosiglitazone (Avandia®) and pioglitazone (Actos®), which work to lower blood sugar levels by increasing the body's sensitivity to insulin. They are taken in pill form and usually used second-line, in combination with other medications such as metformin, a sulfonylurea, or insulin.

Common side effects of thiazolidinediones include weight gain and swelling of the feet and ankles. There is a small but serious increased risk of developing or worsening heart failure related to the use of thiazolidinediones. An early sign of heart failure is swelling of the feet and ankles. People who take thiazolidinediones should monitor for swelling. Other treatments for type 2 diabetes (eg, metformin, insulin, sulfonylureas) may be recommended in people who are at increased risk of heart failure.

In addition, there is a small increase risk of bone fractures related to the use of thiazolidinediones. For this reason, these drugs may not be recommended for women with low bone density (eg, osteopenia or osteoporosis) or other risk factors for fracture.

Use of rosiglitazone may be associated with an increased risk of having a heart attack. This association has not been seen with pioglitazone. Until additional studies provide more information, experts recommend not using rosiglitazone.

GLP-agonists — Exenatide (Byetta®) is an injectable medication that is taken twice per day. It is not a first-line medication, but may be considered for people whose blood sugar is not controlled on the highest dose of one or two oral medications. It may be especially helpful for overweight patients who are gaining weight on oral medications. It must be taken in addition to an oral medication.

Exenatide does not usually cause low blood sugar. Exenatide promotes weight loss, but can also cause bothersome side-effects, including nausea, vomiting, and diarrhea. It is more expensive than insulin therapy. Because it is a relatively new drug, long-term risks and benefits are not known.

Meglitinides — Meglitinides include repaglinide (Prandin®) and nateglinide (Starlix®). They work to lower blood sugar levels, similar to the sulfonylureas, and may be used in people who are allergic to sulfa-based drugs. They are taken in pill form. These medications are not generally used as a first-line treatment because they are more expensive than sulfonylureas and are short-acting, so they must be taken with each meal.

Alpha-glucosidase inhibitors — These medications, which include acarbose (Precose®) and miglitol (Glyset®), work by interfering with the absorption of carbohydrates in the intestines. This results in lower blood sugar levels, though are not as effective as metformin or the sulfonylureas. They can be combined with other medications if the first medication does not lower blood sugar levels sufficiently.

The main side effects of alpha-glucosidase inhibitors are gas (flatulence), diarrhea, and abdominal pain; starting with a low dose may minimize these side effects. The medication is usually taken three times per day with the first bite of each meal.

LIVING WITH TYPE 2 DIABETES

People with type 2 diabetes often experience significant stress related to their disease and the increased responsibilities that come with diabetes, including blood sugar testing, watching the diet, exercise, doctor visits, the need for medication, and the potential risks of complications. It is not uncommon to become depressed as a result of this stress, and this can make taking care of oneself more difficult.

Committing to new treatments and lifestyle changes can be difficult, and it is not uncommon to feel that the benefits of treatment are not worth the effort. Having an open and honest discussion with a doctor or nurse can help you to understand your diagnosis and the need for treatment.

Involving family and friends can help you to manage your disease by offering reminders to take medication, test blood sugar levels, and providing a ride to appointments. Family and friends can also give encouragement and support to eat a healthy diet and stick with an exercise plan.

Working with a psychotherapist or social worker can help you cope with new responsibilities and worries. A number of studies have shown that people who have psychotherapy in addition to traditional medical care have reduced stress and improved blood sugar control compared to people who received only traditional care [1].

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Diabetes mellitus type 2: Overview
Patient information: Diabetes mellitus type 2: Insulin treatment
Patient information: Type 2 diabetes mellitus and diet
Patient information: Self-blood glucose monitoring in diabetes mellitus
Patient information: Hypoglycemia (low blood sugar) in diabetes mellitus
Patient information: Diabetes mellitus type 2: Alcohol, exercise, and medical care
Patient information: Preventing complications in diabetes mellitus

Professional Level Information:
Alpha-glucosidase inhibitors and lipase inhibitors for treatment of diabetes mellitus
Estimation of blood glucose control in diabetes mellitus
Glycemic control and vascular complications in type 2 diabetes mellitus
Insulin therapy in type 2 diabetes mellitus
Management of persistent hyperglycemia in type 2 diabetes mellitus
Metformin in the treatment of diabetes mellitus
Overview of medical care in adults with diabetes mellitus
Sulfonylureas and meglitinides in the treatment of diabetes mellitus
Thiazolidinediones in the treatment of diabetes mellitus

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• National Institute of Diabetes and Digestive and Kidney Diseases

      (www.niddk.nih.gov/)

• American Diabetes Association (ADA)

      (800)-DIABETES (800-342-2383)
      (www.diabetes.org)

• Canadian Diabetes Associates

      (www.diabetes.ca)

• US Center for Disease Control and Prevention

      (www.cdc.gov/diabetes)

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