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* This is the Consumer Version. *

Drug Treatment of Diabetes Mellitus

By Preeti Kishore, MD, Albert Einstein College of Medicine

Many people with diabetes require drugs to lower blood glucose levels, relieve symptoms, and prevent complications.

There are two types of diabetes mellitus, type 1 and type 2.

People with type 1 diabetes require insulin injections to lower blood glucose levels. A few people with type 2 diabetes can control blood glucose levels with only diet and exercise but most require drugs by mouth to lower blood glucose levels and sometimes also insulin.

Doctors must be careful when treating diabetes with drugs because insulin and many of the drugs given by mouth can make blood glucose levels too low ( hypoglycemia).

Insulin Replacement Therapy

People with type 1 diabetes almost always require insulin therapy, and many people with type 2 diabetes require it as well. Usually, insulin is injected into the skin. For certain people, inhaled insulin is also available, although it is not used commonly. Insulincurrently cannot be taken by mouth because insulin is destroyed in the stomach. New forms of insulin, such as forms that can be taken by mouth or applied to the skin, are being tested.

Insulin is injected under the skin into the fat layer, usually in the arm, thigh, or abdomen. Small syringes with very thin needles make the injections nearly painless.

An air pump device that blows the insulin under the skin is rarely used but can be helpful for people who cannot tolerate needles.

An insulin pen, which contains a cartridge that holds the insulin, is a convenient way for many people to carry and use insulin, especially for people who take several injections a day outside the home.

Another device is an insulin pump, which pumps insulin continuously from a reservoir through a small needle left in the skin. Additional doses of insulin can be released at programmed times, or release can be triggered as needed. The pump more closely mimics the way the body normally produces insulin. Pump therapy is considered in some people who require more than three injections per day. For some people, the pump offers an added degree of control, whereas others find wearing the pump inconvenient or develop sores at the needle site.

Insulin forms

Insulin is available in three basic forms, divided by speed of onset and duration of action:

  • Rapid-acting insulin, such as regular insulin, is fast and short acting. Regular insulin reaches its maximum activity in 2 to 4 hours and works for 6 to 8 hours. Lispro, aspart, and glulisine insulins, special types of rapid-acting regular insulin, are the fastest of all, reaching maximum activity in about 1 hour and working for 3 to 5 hours. Rapid-acting insulin is often used by people who take several daily injections and is injected 15 to 20 minutes before meals or just after eating.

  • Intermediate-acting insulin (such as neutral protamine Hagedorn [NPH] or neutral protamine lispro [NPL] insulin) starts to work in 1 to 3 hours, reaches its maximum activity in 6 to 10 hours, and works for 15 to 26 hours. This type of insulin may be used in the morning to provide coverage for the first part of the day or in the evening to provide coverage during the night.

  • Long-acting insulin (such as insulin glargine, detemir, or degludec) has very little effect in the first few hours but provides coverage for 20 to 36 hours depending on which of these types is used.

Inhaled insulin is available for use in some situations for people who are unable or unwilling to take insulin injections. Inhaled insulin is available as an inhaler (similar to an asthma inhaler), and people inhale the insulin into the lungs for absorption. Inhaled insulin works similar to short-acting insulin and needs to be taken several times per day. People also need to take injections of long-acting insulin. While people are using inhaled insulin, doctors check their lung function every 3 months.

Insulin preparations are stable at room temperature for months, allowing them to be carried, brought to work, or taken on a trip. Insulin should not, however, be exposed to extreme temperatures.

Choice of insulin

The choice of insulin is complex. The following factors are considered before deciding which insulin is best:

  • How willing and able people are to monitor their blood glucose levels and adjust their insulindosage

  • How often people are willing to inject insulin

  • How varied daily activity is

  • How adept people are at learning about and understanding the disorder

  • How stable blood glucose levels are during the day and from day to day

The easiest regimen to follow is a single daily injection of an intermediate-acting insulin. However, such a regimen provides the least control over blood glucose levels and is, therefore, rarely the best approach.

Stricter blood glucose control may be achieved by combining two insulins—a rapid-acting and an intermediate-acting insulin—in one morning dose. This combination requires more skill, but it offers people greater opportunity to adjust the blood glucose levels. A second injection of one insulin or both may be taken at dinner or at bedtime.

Strictest blood glucose control is usually achieved by injecting a long-acting insulin in the morning or evening along with several additional injections of rapid-acting insulin during the day. Adjustments can be made as insulin needs change. Measuring blood glucose levels at various times during the day helps determine the adjustment. Although this regimen requires the most knowledge about diabetes and attention to the details of treatment, it is considered the best option for most people who are treated with insulin, especially people with type 1 diabetes.

Some people, especially older people, take the same amount of insulin every day. Other people adjust the insulin dose daily depending on their diet, exercise, and blood glucose patterns. In addition, insulin needs may change if people gain or lose weight or experience emotional stress or illness, especially infection.

Insulin resistance

Over time, some people develop resistance to insulin. Because the injected insulin is not exactly like the insulin the body manufactures, the body can produce antibodies to the insulin. Although this reaction is less common with newer insulinpreparations, these antibodies may interfere with the insulin’s activity, requiring very large doses.

Allergic reaction to insulin

Insulininjections can affect the skin and underlying tissues. An allergic reaction, which occurs rarely, causes pain and burning, followed by redness, itchiness, and swelling around the injection site for several hours. More commonly, the injections either cause fat deposits, making the skin look lumpy, or destroy fat, causing indentation of the skin. Many people rotate the injection sites, for example, using the thigh one day, the stomach another, and an arm the next, to avoid these problems.

Oral Antihyperglycemic Drugs

Oral antihyperglycemic drugs can often lower blood glucose levels adequately in people with type 2 diabetes. However, they are not effective in type 1 diabetes. There are several types, but antihyperglycemic drugs are often divided into two major classes.

  • Insulin secretagogues, which stimulate the pancreas to produce more insulin

  • Insulin sensitizers, which do not affect the release of insulin but increase the body’s response to it

Insulin secretagogues include sulfonylureas (for example, glyburide) and meglitinides (for example, repaglinide).

Insulin sensitizers include biguanides (for example, metformin) and thiazolidinediones (for example, rosiglitazone).

Glucosidase inhibitors (for example, acarbose) are another class of drugs, which work by delaying absorption of glucose in the intestine.

People with type 2 diabetes are often prescribed oral antihyperglycemic drugs if diet and exercise fail to lower the levels of glucose in the blood adequately. The drugs are sometimes taken only once a day, in the morning, although some people need two or three doses. More than one type of oral drug may be used if one is not adequate. If oral antihyperglycemic drugs cannot control blood glucose levels well enough, injections of insulin or glucagon-like peptide drugs alone or in combination with the oral drugs may be needed.

Oral Antihyperglycemic Drugs

Drug

Number of Doses

Some Side Effects

Biguanides

Metformin

2 to 3 per day

Diarrhea

Increased acidity of body fluids (rare)

Liver failure (rare)

Extended-release metformin

1 to 2 per day

Sulfonylureas

Chlorpropamide

1 per day

Low sodium in blood

Glimepiride

1 per day

Low blood glucose levels

Dizziness

Headache

Glipizide

1 to 2 per day

Diarrhea

Nausea

Low blood glucose levels

Low blood count (anemia)

Glyburide

1 to 2 per day

Low blood glucose levels

Indigestion

Weight gain

Micronized glyburide

1 to 2 per day

Low blood glucose levels

Indigestion

Weight gain

Tolazamide

1 to 2 per day

Low blood glucose levels

Nausea

Vomiting

Tolbutamide

1 to 2 per day

Low blood glucose levels

Headache

Low blood count

Meglitinides

Nateglinide

3 per day

Minimal weight gain

Repaglinide

3 per day

Low blood glucose levels

Thiazolidinediones

Pioglitazone

1 per day

Weight gain

Fluid retention (edema)

Increased risk of fractures

Rosiglitazone

1 to 2 per day

Weight gain

Fluid retention

Increased risk of fractures

Possible increase in heart attacks

Alpha-glucosidase inhibitors

Acarbose

3 per day

Diarrhea

Abdominal pain

Bloating

Miglitol

3 per day

Diarrhea

Abdominal pain

Bloating

Dipeptidyl peptidase-4 inhibitor

Alogliptin

1 per day

Upper respiratory infections

headache

Inflamed pancreas

Joint pain

Linagliptin

1 per day

Upper respiratory infections

Diarrhea

Inflamed pancreas

Saxagliptin

1 per day

Upper respiratory infections

Urinary tract infections

Inflamed pancreas

Sitagliptin

1 per day

Headache

Diarrhea

Lung infections

Sodium-glucose co-transporter-2 (SGLT2) inhibitor

Canagliflozin

1 per day

Increased cholesterol levels in the blood

Urinary tract infections

Genital fungal infections

Dapagliflozin

1 per day

Urinary tract infections

Fungal infections of the genitals

Possible increased risk of bladder cancer

Empagliflozin

1 per day

Low blood pressure

Urinary tract infection

Genital fungal infection

Kidney impairment

Injectable Antihyperglycemic Drugs

Insulin is the most commonly used injectable antihyperglycemic drug. Its use is discussed above.

There are two other types of injectable antihyperglycemic drugs

  • Glucagon-like peptide drugs

  • Amylin-like drugs

Glucagon-like peptide drugs (GLP-1 drugs) work mainly by increasing insulin secretion by the pancreas. These drugs also slow the passage of food out of the stomach (which slows the rise of blood glucose). These drugs may also reduce appetite and promote weight loss. GLP-1 drugs are given by injection before meals. They may be used in combination with oral antihyperglycemic drugs in people with type 2 diabetes when oral antihyperglycemic drugs do not control blood glucose levels well enough.

Amylin-like drugs mimic the action of amylin, a pancreatic hormone that helps regulate blood glucose levels after eating. Pramlintide is currently the only available amylin-like drug. It suppresses secretion of the hormone glucagon. Because glucagon increases blood glucose, pramlintide thus helps lower blood glucose. It also slows the passage of food out of the stomach and helps people feel full. It is given by injection and is used in combination with mealtime insulin in people with type 1 or type 2 diabetes.

Injectable Antihyperglycemic Drugs*

Drug

Number of Doses

Some Side Effects

Glucagon-like peptide drugs

Albiglutide

1 per week

Upper respiratory infection

Diarrhea

Nausea

Joint pain

Thyroid tumors

Inflamed pancreas

Kidney damage

Dulaglutide

1 per week

Nausea

Diarrhea

Rapid heart beat

Thyroid tumors

Inflamed pancreas

Exenatide

2 per day

Nausea

Vomiting

Extended release exenatide

1 per week

Nausea

Diarrhea

Injection site nodule

Thyroid tumors

Liraglutide

1 per day

Inflamed pancreas

Thyroid tumors

Nausea

Diarrhea

Vomiting

Amylin-like drug

Pramlintide

3 per day

Nausea

Low blood glucose levels

* Insulin is the most commonly used injectable antihyperglycemic drug.

More Information

Resources In This Article

Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • ONGLYZA
  • DIABINESE
  • No US brand name
  • AVANDIA
  • PRANDIN
  • JANUVIA
  • SYMLIN
  • GLUCOTROL
  • TRADJENTA
  • AMARYL
  • DIABETA, GLYNASE
  • ACTOS
  • GLYSET
  • PRECOSE
  • BYETTA
  • GLUCOPHAGE
  • STARLIX
  • VICTOZA

* This is the Consumer Version. *