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Dual Gastric Inhibitory Polypeptide (GIP) and Glucagon-like Peptide-1 (GLP-1) Receptor Agonists

Reviewed by: HU Medical Review Board | Last reviewed: August 2023

Gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) are hormones involved in controlling blood sugar (glucose). Your doctor may prescribe a drug that helps mimic GIP and GLP-1.

Drugs that mimic GLP-1 alone are called GLP-1 receptor agonists. Drugs that mimic both GLP-1 and GIP are called dual GIP-GLP1 receptor agonists.

Both types of drugs can treat people with type 2 diabetes (T2D). The drugs lower blood sugar by triggering the pancreas to release insulin after meals. These drugs are used in combination with lifestyle changes like diet and exercise.1-4

These drugs are not used as a first-line treatment for T2D. These are most often used when other treatments do not control blood sugar enough.

How do GLP-1 and dual GIP-GLP1 receptor agonists work?

Blood sugar levels depend on the activity of several hormones. Some of these hormones include:1

  • Insulin, which transports glucose out of the bloodstream
  • Glucagon, which causes the liver to release glucose into the bloodstream
  • Incretins, which trigger the release of insulin from the pancreas

GLP-1 and GIP are both incretin hormones. They are released by the intestines after you eat a meal. They then bind to proteins called the GLP-1 receptor and the GIP receptor. This causes the pancreas to release insulin, which reduces blood sugar.2,3,5

People with T2D release low levels of GLP-1 and GIP after eating. Taking drugs that activate the GLP-1 receptor or both receptors may help lower blood sugar. The drugs work by:1,4,6

  • Increasing the amount of insulin released by the pancreas after meals
  • Slowing the rate of food moving through your stomach (gastric emptying)
  • Reducing the amount of glucagon made by the liver

GLP-1 receptor agonists and dual GIP-GLP1 receptor agonists can lead to weight loss. And losing weight may help lower the risk of heart problems and overall mortality. GLP-1 receptor agonists are useful for people with T2D who are carrying extra weight or have heart disease.1,7

Examples of GLP-1 and dual GIP-GLP1 receptor agonists for T2D

Examples of GLP-1 receptor agonists include:4

  • Byetta® (exenatide)
  • Bydureon® (exenatide ER)
  • Adlyxin® (lixisenatide)
  • Victoza® (liraglutide)
  • Trulicity® (dulaglutide)
  • Ozempic®, Rebelsus® (semaglutide)

Mounjaro® (trizepatide) is one example of a dual GIP-GLP1 receptor agonist.8

The choice of which drugs to use depends on a number of factors, including:4

  • Whether you have other medical conditions
  • Whether you have side effects
  • Preference for self-injecting or oral drug form
  • Personal preference
  • Cost

What are the possible side effects?

Common side effects include:1,3,8

  • Vomiting
  • Diarrhea
  • Dizziness
  • Headache
  • Injection site reactions
  • Constipation
  • Weakness

More serious side effects are possible, including:1,3,8

  • Pancreas inflammation (pancreatitis)
  • Kidney problems
  • Low blood sugar
  • Gallbladder disease
  • Allergic reactions
  • Low blood platelet count
  • Thyroid tumors

These are not all the possible side effects of GLP-1 and dual GIP-GLP1 receptor agonists. Talk to your doctor about what to expect when taking them. You also should call your doctor if you have any changes that concern you when taking GLP-1 or dual GIP-GLP1 receptor agonists.

Other things to know

Take GLP-1 and dual GIP-GLP1 receptor agonists exactly as your doctor prescribes. Most versions are self-injected using a prefilled injector pen. Semaglutide also comes as a pill.1

Your doctor may start you at a low dose to avoid side effects, then slowly increase the dose as needed. If you have side effects, they may switch you to a different version. Longer-acting (once-weekly) versions have a lower risk of side effects.1

Your doctor may combine GLP-1 or dual GIP-GLP1 receptor agonists with other T2D treatments. But these receptor agonists cannot be combined with dipeptidyl peptidase 4 (DPP-4) inhibitors.1

Some GLP-1 or dual GIP-GLP1 receptor agonists should not be used if you have other medical conditions. In general, you should not use them if you:1,4

  • Have a history of pancreatitis
  • Have type 1 diabetes
  • Have severe gastrointestinal disease
  • Are allergic to the drug's ingredients
  • Are pregnant

Unfortunately, GLP-1 receptor agonists are the most expensive drug for T2D. They typically cost $500 to $700 for a 30-day supply. However, this is cheaper than hospital stays and treatment for diabetes complications. These are still valuable treatment options.4

Before beginning treatment for T2D, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.

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