Incretin Based Treatments

doctor and patient

Incretin based treatments reduce post meal blood sugars.

These medicines are also euglycemics, which help return the blood sugar to the normal range.

When you have type 2 diabetes, the blood sugar may be too high after a meal, even if you eat very little carbohydrate (CHO). This, in part, is due to glucagon levels staying too high after meals.

Medicines, called incretin based treatments, are now available to control post-meal glucagon, and help reduce the post meal blood sugars. These medicines also are blood sugar normalizing medications or euglycemics (drugs that help return the blood sugar to the normal range). The incretin based medicines are available in two families of medicines: DPP-4 Inhibitors and GLP-1 analogs. Sitagliptin, saxagliptin, and linagliptin (approved May 2011 and is not available yet) are DPP-4 inhibitors and are taken as pills. Exenatide and liraglutide are GLP-1 analogs and are taken by injection.

If you have kidney problems, the dose of the incretin based medicines may need to be adjusted. Please tell your doctor if you have kidney problems before starting these medicines.

DPP-4 Inhibitors

DPP-4 inhibitors are oral medicines for people with type 2 diabetes that help control blood sugar levels, especially after eating. After eating, your gut naturally releases hormones—two important ones are GLP-1 and GIP. These hormones increase insulin release to help control blood sugar levels. GLP-1 also decreases glucagon release at meals, to further control blood sugar levels. However, these hormones are quickly broken down in the body by an enzyme called DPP-4. DPP-4 inhibitors like sitagliptin and saxagliptin block DPP-4 from breaking down GLP-1 as quickly so that GLP-1 can have a longer effect in the body.

While DPP-4 inhibitors may be used as an initial choice for a medicine to help lower blood sugar levels, they are mainly being used in combination with other diabetes medicines. This means that these medicines are usually added on when a person is already taking one or two medicines for diabetes, but their sugars are still not well controlled.

Unlike with exenatide and liraglutide, people do not typically lose weight with DPP-4 inhibitors. Fortunately, these medicines do not cause weight gain.

Sitagliptin (Januvia®)

Sitagliptin is approved by the Food and Drug Administration (FDA) for combined use with metformin, insulin releasing pills, thiazolidinediones, and insulin.

In short, sitagliptin lowers glucagon levels after meals, which then reduces the amount of sugar released from the liver, and also increases insulin release from the pancreas when the blood sugar becomes too high after meals.

The most common side effects are:

  • Sore throat
  • Runny nose
  • Upper respiratory infections
  • Low blood sugar, when taken together with insulin releasing pills and insulin

Uncommon side effects:

  • Hypersensitivity reactions including allergic reactions, mouth and throat swelling and skin rashes
  • Sitagliptin, has been reported to rarely cause pancreatitis, a serious condition. If you experience nausea, vomiting, anorexia, and persistent severe abdominal pain (which may travel to your back), contact your medical provider right away.

Contact your medical provider right away if you have side effects.

Ask your medical provider for specific medicine and insulin dose adjustment recommendations to avoid low blood sugars.

Saxagliptin (Onglyza®)

Saxagliptin is approved by the Food and Drug Administration (FDA) for use in people with type 2 diabetes, along with diet and exercise.

In short, saxagliptin lowers glucagon levels after meals, which then reduces the amount of sugar released from the liver, and increases insulin release from the pancreas when the blood sugar becomes too high after meals.

The most common side effects are:

  • Upper respiratory tract infections
  • Urinary tract infections (bladder infection)
  • Headache
  • If used with a thiazolidinedione (such as pioglitazone), swelling or fluid retention may occur or become worse.
  • If used with an insulin secretor (such as a sulfonylurea), the chance for a low blood sugar (hypoglycemia) may become worse.

Uncommon, but serious side effects are:

  • Allergic (hypersensitivity) reactions, such as rash, hives, and swelling of the face, lips, and throat
  • Sitagliptin, another medicine in the family of DPP-4 inhibitors, has been reported to rarely cause pancreatitis, a serious condition. If you experience nausea, vomiting, anorexia, and persistent severe abdominal pain (which may travel to your back), contact your medical provider right away.

Contact your medical provider right away if you have side effects.

Saxagliptin may negatively interact with other medicines, such as certain antibiotics, medicines that treat fungus infections or HIV/AIDS. Be sure to alert your medical provider if you will be starting or stopping any of these types of medicines, as the dose of saxagliptin might need to be changed.

Ask your medical provider for specific medication and insulin dose adjustment recommendations to avoid low blood sugars.

Linagliptin (Trajenta®)

Linagliptin has recently been approved by the Food and Drug Administration (FDA) for use in people with type 2 diabetes, along with diet and exercise. Like saxagliptin and sitagliptin, linagliptin is a DPP-4 inhibitor. Linagliptin will be available in pharmacies on 5/20/2011.

GLP-1 Analogs

GLP- 1 analogs are injected medicines for people with type 2 diabetes that helps prevent the blood sugar from rising after eating. GLP- 1 analogs act like a natural hormone, GLP-1, that is released in the gut when we eat. When you have type 2 diabetes, GLP-1 doesn’t work on the pancreas properly and post-meal glucagon levels stay too high. GLP-1 also delays emptying of food from the stomach and promote a feeling of satiety (satisfaction of having eaten enough).

The natural hormone GLP-1 is normally broken down very quickly in the bloodstream by enzymes known as DPP-4. GLP-1 analogs were developed to resist breakdown by the enzyme DPP-4, this way the medicine lasts longer in the blood stream and the GLP-1-like action lasts longer.

Exenatide (Byetta®)

Exenatide is an injected medicine administered twice daily. It is not insulin. A once weekly form of exenatide has been studied and may become available shortly.

Exenatide is approved by the Food and Drug Administration (FDA) to treat adults with type 2 diabetes, along with diet and exercise. It is also approved for use in combination with metformin, thiazolidinediones and insulin secretagogues.

In short, exenatide lowers glucagon during a meal, slows food emptying from the stomach, curbs appetite and increases insulin release from the pancreas when the blood sugar is too high.

The most common side effects when starting exenatide are:

  • Nausea
  • Vomiting
  • Low blood sugars

Uncommon side effects:

  • May cause pancreatitis, which presents as severe abdominal pain that won’t go away.

If you experience any side effects, contact your medical provider immediately.

Give your body a chance to adjust to this new medicine slowly. The starting dose is 5 micrograms twice daily, taken at breakfast and dinner. After 1 month, if you are tolerating exenatide, the dose may be increased to 10 micrograms, twice daily. It is available in a disposable pen device.

Some people can lose a small amount of weight while taking exenatide.

If you are treated with insulin releasing pills or insulin and starting exenatide, it is important to remember:

  • The insulin releasing pill dose may need to be lowered, ask your medical provider for exact recommendation. Inject exenatide up to 1 hour before eating; it is taken at breakfast and dinner.
  • Exenatide is not yet approved by the FDA for use in insulin treated individuals. However, if you are taking exenatide in combination with insulin therapy, the insulin dose should be decreased. Ask your provider for specific recommendations regarding the insulin dose adjustment.

For more information about incretin therapy formulations, initial and final doses, and side effects, see our Medications Table.

Liraglutide (Victoza®)

Liraglutide is an injected medicine, administered once daily. It is not insulin. Liraglutide is not recommended as the first choice of medicine for treating diabetes. Liraglutide is approved by the Food and Drug Administration (FDA) to treat adults with type 2 diabetes, along with diet and exercise.

In short, liraglutide lowers glucagon during a meal, slows food emptying from the stomach, curbs appetite and increases insulin release from the pancreas when the blood sugar is too high.

The most common side effects when starting liraglutide are:

  • Nausea
  • Headache
  • Diarrhea
  • Low blood sugar

Uncommon side effects:

  • Antibody formation to the medication
  • Hives, other allergic and immune reactions
  • May cause pancreatitis, presents as severe abdominal pain that won’t go away
  • May cause medullary thyroid cancer in certain predisposed individuals, report lump or swelling of neck, hoarseness, or difficulty swallowing

If you experience any side effects, contact your medical provider immediately.

Caution:

Give your body a chance to adjust to this new medicine slowly. The starting dose is 0.6 mg once daily, the maximum dose is 1.8 once daily. If you are tolerating liraglutide, the dose may be increased by 0.6 mg increments every week — up to a maximum of 1.8 mg daily — until you meet your blood sugar goals. It is available in a disposable pen device.

If you are treated with insulin releasing pills or insulin and starting liraglutide, it is important to remember:

  • The dose of the insulin releasing pill may need to be lowered, ask your medical provider for exact recommendation.
  • Liraglutide is not yet approved by the FDA for use in insulin treated individuals. However, if you are taking liraglutide in combination with insulin therapy, the insulin dose should be decreased. Ask your provider for specific recommendations regarding the insulin dose adjustment.

For more information about incretin therapy formulations, initial and final doses, and side effects, see our Medications Table

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