GLP-1 receptor agonists are a type of non-insulin medication that is used in combination with diet and exercise to help treat type 2 diabetes. These drugs are prescribed to help lower blood glucose levels and hemoglobin A1C and to aid in weight loss. Research has shown that GLP-1 receptor agonists can have other health benefits on blood pressure, cholesterol levels, and beta-cell function.

These injectable drugs are usually prescribed along with oral diabetes medicines or insulin therapy. They aren’t regarded as first-line treatment in diabetes, but they can be a valuable part of the overall management plan.

How They Work

Glucagon-like peptide (GLP-1) is a type of hormone known as an incretin that’s lower than normal in type 2 diabetes. GLP-1 receptor agonists belong to a class of medications known as incretin mimetics.

Type 2 Diabetes Doctor Discussion Guide

Get our printable guide for your next healthcare provider’s appointment to help you ask the right questions.

Sign up for our Health Tip of the Day newsletter, and receive daily tips that will help you live your healthiest life.

Thank you, {{form.email}}, for signing up.

There was an error. Please try again.

By mimicking the effects of GLP-1, the GLP-1 receptor agonists have many effects.

Some of their actions include:

  • Help control appetite and blood sugar levelsHelp the pancreas release the optimal amount of insulin, which transports glucose (sugar) to tissues in the body where it can be used for energySlow the rate at which food leaves the stomach, which helps to control post-prandial (after-meal) blood sugar levels

GLP-1 agonists work on different organs throughout the body.

Brain

GLP-1 sends a signal to the hypothalamus, the part of the brain responsible for appetite and thirst, to take in less water and food. This can lead to weight loss.

Muscle

GLP-1 stimulates gluconeogenesis, which is the process the body uses to make glucose from protein or fat. This process lowers blood sugar by stimulating glucose uptake into the cells and increasing how efficiently the body uses insulin.

Dehydration Danger

Because GLP-1 receptor agonists dampen thirst, it’s vital to drink plenty of water and other fluids to stay hydrated while taking these medications.

Pancreas

When GLP-1 encounters glucose, the pancreas is triggered to secrete more insulin, which lowers the amount of post-meal glucose in the blood.

GLP-1 also decreases the secretion of glucagon—a pancreatic hormone that helps to prevent blood sugar levels from dipping too low. In people with type 2 diabetes, glucagon can cause blood glucose levels to become too high.

Liver

GLP-1 lowers hepatic (liver) glucose output, which helps lower blood sugar levels.

As gluconeogenesis increases, glucagon receptors are reduced in the liver, inhibiting glucose formation and stimulating glucose uptake by cells, thus lowering the amount of glucose in the blood.

Stomach

GLP-1 decreases both the secretion of acid in the stomach and how quickly food is emptied from the stomach, prolonging the sensation of fullness. This can limit how much a person eats and may ultimately lead to weight loss.

The Different GLP-1 Receptor Agonists

There are two types of GLP-1 receptor agonist: short-acting formulas that typically are taken once or twice a day, and long-acting formulas, which are taken once a week. The type prescribed is based on a number of factors, including medical history, blood sugar control, insurance coverage, price (GLP-1 receptor agonists can be expensive), and personal preference.

Administration

Most GLP-1 receptor agonist medications are injectable, meaning they’re given with a syringe and needle or with a pre-filled dosing pen, depending on the drug. Both short-lasting or long-lasting GLP-1 receptor agonist shots are subcutaneous—inserted into the fatty tissue just below the surface of the skin.

If your healthcare provider prescribes a GLP-1 receptor agonist, they will teach you how to inject it yourself into either your abdomen or upper thigh. If you’re unable to give yourself a shot, someone else can administer the drug into your upper arm.

To self-inject a GLP-1 receptor agonist medication:

  • Examine the solution to make sure it’s clear, colorless, and has no floating particles. Check the label to make sure the expiration date has not passed.Gather your supplies: an alcohol pad, bandage, gauze, or tissue, and your prepared or mixed medication in a pen or vial and syringe.Wash your hands.Use the alcohol pad to clean the area where you’ll give the injection; rotate injection sites so that you aren’t sticking the same area over and over.Draw up your correct dose, either in the prefilled pen or syringe.Take a large pinch of skin and pull it away from the muscle underneath.Holding the pen or syringe like a dart, quickly insert the needle at a 90-degree angle to the skin.Slowly inject the medication.Release the skin, then withdraw the needle.Apply bandage, gauze, or tissue as necessary.

Side Effects

Overall, GLP-1 receptor agonists are safe and cause few side effects.

Never reuse or share supplies. You should draw up your medication into a fresh syringe every time you self-inject. Most pre-filled pens should be discarded after 30 days, even if they are unused. You can talk to your pharmacist about proper disposal of these supplies.

Common Side Effects

These include nausea, vomiting, and diarrhea, which affect 10 percent to 40 percent of people who take a GLP-1 receptor agonist. They are most likely to occur with short-acting medications and tend to be less severe the longer a person takes the medication.

Other potential side effects of GLP-1 receptor agonists include constipation, bloating, indigestion, and headache. There also can be some redness, itching, or soreness of the skin at the injection site.

Serious Side Effects

Although rare, these side effects should be treated as an emergency:

  • Ongoing abdominal or back pain, with or without vomitingA skin rash or hivesItchingPounding heartDizziness or faintingSwelling of the eyes, face, mouth, tongue, throat, feet, ankles, or lower legsTrouble swallowing or breathingHoarsenessDecreased urinationVery dry mouth or skinExtreme thirst

Complications

In animal studies, both liraglutide and dulaglutide have been shown to promote thyroid cell tumors. Although these drugs haven’t been evaluated in humans for this potential complication, it is recommended that people with a history of or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 do not use GLP-1 receptor agonists.

With certain GLP-1 receptor agonists, there is a possible small increased risk of pancreatitis (inflammation of the pancreas).

Who Should Avoid Them?

This medication is not recommended for people who:

  • Have a history of pancreatitis
  • Have a history of gastroparesis (paralysis of the stomach)
  • Have medullary thyroid cancer or multiple endocrine neoplasia type 2 or a family history of these conditions
  • Are on dialysis (as the safety of using GLP-1 agonists in this situation hasn’t been proven)

In addition, people with impaired kidney function due to diabetes who have a GFR (glomerular filtration rate) of 30 or less should not use Bydureon or Byetta but may be able to take another GLP-1 receptor agonist.

A Word From Verywell

Living with type 2 diabetes means that you have to watch your diet, and you may need to take medication for the rest of your life. That said, controlling your blood sugar and weight can prevent complications of this very common disorder. A GLP-1 receptor agonist might be part of your overall treatment plan to help you live a healthy life.

Frequently Asked Questions

  • What is a GLP-1 agonist?
  • Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications used to treat type 2 diabetes. GLP-1 is an incretin hormone that helps the pancreas release insulin. People with type 2 diabetes have lower levels of incretin hormones, which leads to high blood sugar. GLP-1 receptor agonists include:Adlyxin (lixisenatide)Bydureon (exenatide)Byetta (exenatide)Ozempic (semaglutide)Rybelsus (semaglutide)Saxenda (liralutide) Trulicity (dulaglitide)Victoza (liraglutide)Wegovy (semaglutide)
  • Do GLP-1 agonists help to lower A1c levels?
  • Yes, research shows GLP-1 agonists help lower A1c levels by about 1% in people with type 2 diabetes. These medications lower fasting blood sugar levels and reduce post-meal blood sugar spikes without increasing the risk of hypoglycemia.
  • Are there any oral GLP-1 agonists for people with type 2 diabetes?
  • Yes, Rybelsus (semaglutide) is an oral GLP-1 receptor agonist that is FDA approved for treating type 2 diabetes. Side effects for Rybelsus include abdominal pain, constipation, decreased appetite, diarrhea, nausea, and vomiting.

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications used to treat type 2 diabetes. GLP-1 is an incretin hormone that helps the pancreas release insulin. People with type 2 diabetes have lower levels of incretin hormones, which leads to high blood sugar. 

Yes, research shows GLP-1 agonists help lower A1c levels by about 1% in people with type 2 diabetes. These medications lower fasting blood sugar levels and reduce post-meal blood sugar spikes without increasing the risk of hypoglycemia.

Yes, Rybelsus (semaglutide) is an oral GLP-1 receptor agonist that is FDA approved for treating type 2 diabetes. Side effects for Rybelsus include abdominal pain, constipation, decreased appetite, diarrhea, nausea, and vomiting.

  • Del Olmo-Garcia MI, Merino-Torres JF. GLP-1 Receptor Agonists and Cardiovascular Disease in Patients with Type 2 Diabetes. J Diabetes Res. 2018;2018:4020492. doi:10.1155/2018/4020492
  • Dungan K, DeSantis A. Glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes mellitus.
  • Prasad-Reddy L, Isaacs D. A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond. Drugs Context. 2015;4:212283. doi:10.7573/dic.212283
  • McKay NJ, Kanoski SE, Hayes MR, Daniels D. Glucagon-like peptide-1 receptor agonists suppress water intake independent of effects on food intake. Am J Physiol Regul Integr Comp Physiol. 2011;301(6):R1755–R1764. doi:10.1152/ajpregu.00472.2011
  • Gupta V. Glucagon-like peptide-1 analogues: An overview. Indian J Endocrinol Metab. 2013;17(3):413–421. doi:10.4103/2230-8210.111625
  • Tran KL, Park YI, Pandya S, et al. Overview of glucagon-like peptide-1 receptor agonists for the treatment of patients with type 2 diabetes. Am Health Drug Benefits. 2017;10(4):178–188.
  • Romera I, Cebrián-Cuenca A, Álvarez-Guisasola F, Gomez-Peralta F, Reviriego J. A Review of Practical Issues on the Use of Glucagon-Like Peptide-1 Receptor Agonists for the Management of Type 2 Diabetes. Diabetes Ther. 2019;10(1):5-19. doi:10.1007/s13300-018-0535-9
  • Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists: a review of head-to-head clinical studies. Ther Adv Endocrinol Metab. 2015;6(1):19-28. doi:10.1177/2042018814559725
  • Hughes S, Neumiller JJ. Oral Semaglutide. Clin Diabetes. 2020;38(1):109-111. doi:10.2337/cd19-0079

By Barbie Cervoni MS, RD, CDCES, CDN

Barbie Cervoni MS, RD, CDCES, CDN, is a registered dietitian and certified diabetes care and education specialist.

  • Meet Our Medical Expert Board

  • About Us

  • Editorial Process

  • Diversity Pledge

  • Privacy Policy

  • In the News

  • Advertise

  • Terms of Use

  • Careers

  • Contact

  • EU Privacy

  • Health A-Z

  • Prevention & Treatment

  • Drugs A-Z

  • Health Care

  • News

  • instagram

  • twitter

  • facebook

  • pinterest

  • flipboard