Glucagon-like Peptide-1 (GLP-1) Agonists

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

Glucagon-like peptide-1 (GLP-1) receptor agonists are drugs that treat people with type 2 diabetes (T2D). They lower blood sugar by triggering the pancreas to release insulin after meals. GLP-1 receptor agonists are used with lifestyle changes like diet and exercise.1-4

GLP-1 receptor agonists are not usually used as a first treatment for T2D. They are most often used when other treatments do not control blood sugar.

How do GLP-1 receptor agonists work?

Blood glucose 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 triggers the release of insulin from the pancreas

GLP-1 is an incretin hormone. It is released by the intestines after you eat a meal. It then binds to a protein called the GLP-1 receptor. This causes the pancreas to release insulin, which reduces blood sugar.2,3

People with T2D release low levels of GLP-1 after eating. This leads to high blood sugar because it impairs the activity of insulin. Taking drugs that mimic GLP-1 may lower blood sugar. These drugs are called GLP-1 receptor agonists. They work by:1,4

  • 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 can lead to weight loss. This lowers 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.1,5

Examples of GLP-1 receptor agonists for type 2 diabetes

Examples of GLP-1 receptor agonists include:4

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

The choice of which one to use depends on a number of factors. Concerns include: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 of GLP-1 receptor agonists include:1,3

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

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

  • 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 receptor agonists. Talk to your doctor about what to expect when taking GLP-1 receptor agonists. You also should call your doctor if you have any changes that concern you when taking GLP-1 receptor agonists.

Other things to know

Take GLP-1 receptor agonists exactly as your doctor prescribes. Most versions are self-injected using a prefilled injector pen. Semaglutide also comes as an oral option.1

You may start at a low dose to avoid side effects. Then you may slowly increase the dose. If you have side effects, you may switch to a different GLP-1 receptor agonist. Longer-acting (once-weekly) versions have a lower risk of side effects.1

Your doctor may combine GLP-1 receptor agonists with other T2D treatments. GLP-1 receptor agonists can be combined with other treatments except dipeptidyl peptidase 4 (DPP-4) inhibitors.1

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

  • Have a history of pancreatitis
  • Have type 1 diabetes
  • Have severe gastrointestinal disease
  • Are allergic to medicine 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 treatments for diabetes complications. GLP-1 receptor agonists 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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