GLP-1 Receptor Agonists for Type 2 Diabetes

Injectable Medications That Lower Blood Sugar and Aid Weight Loss

Updated on April 05, 2024

Medically reviewed by Lindsay Cook, PharmD

GLP-1 receptor agonists are a non-insulin type 2 diabetes medication. GLP-1 agonists help to lower blood sugar and aid in weight loss.

Drugs in this class include Byetta (exenatide), Victoza (liraglutide), Trulicity (dulaglutide), and Ozempic (semaglutide) among others.

A woman checking her diabetes reader — fertnig / istock

Used in combination with diet, exercise, and oral diabetes medicines, these drugs help to lower hemoglobin A1C levels and improve blood pressure, cholesterol levels, and beta-cell function.

This article discusses GLP-1 agonists. It explains how GLP-1s work to treat diabetes and boost weight loss. It also describes the various GLP-1s on the market and the differences between them.

How They Work

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

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

Some of their actions include:

Helping control appetite and blood sugar levels
Helping the pancreas release the optimal amount of insulin, which transports glucose (sugar) to tissues in the body where it can be used for energy
Slowing 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.

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.

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.

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.

Types of GLP-1 Receptor Agonists

There are two types of GLP-1 receptor agonists: short-acting formulas, which 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.

Short-acting GLP-1 Receptor Agonists
Drug Name	Dose	Pros	Cons	Other Considerations
Byetta (exenatide)	5 micrograms (mcg) twice daily the first month; 10 mcg twice a day thereafter	Relatively inexpensive compared to newer GLP-1 agonists	Must be given 60 minutes before a meal, which can sometimes be inconvenient	Because exenatide is excreted through the kidneys, it's not recommended for people with GFRs of 30 or less
Victoza, Saxenda (liraglutide)	0.6 mcg per day the first week; 1.2 mcg daily thereafter, increasing to 1.8 mcg per day if necessary to reach optimal blood glucose levels	Saxenda is indicated for weight loss	Often causes nausea	Saxenda is only covered by certain insurance providers.

Long-acting GLP-1 Receptor Agonists
Drug Name	Dose	Pros	Cons	Other Considerations
Bydureon (exenatide)	2 milligrams (mg) once per week	Comes in a pre-filled pen	Is excreted via the kidneys and should be avoided by anyone with a GFR of 30 or less	Reduces A1C by about 1.5%; the pen can be hard to use and causes a grape-sized ball on the skin
Trulicity (dulaglutide)	0.75 mg weekly; increase to 1.5 mg or up to 4 mg after 6 to 8 weeks	Comes as a pre-filled pen that is easy to use	Not very effective for weight loss; not covered by all insurance providers; can be expensive	Reduces A1C by about 1.4%
Ozempic (semaglutide)	0.25 mg in the first four weeks; 0.5 mg thereafter. If, after 4 weeks, more blood sugar control is needed, the dose can be increased to 1 mg	Has the highest effectiveness for weight loss of all GLP1	As a newer drug, can be pricey; can cause nausea
Wegovy (semaglutide)	0.25 mg weekly for 4 weeks; the dose is increased in 4-week intervals until a weekly dose of 2.4 mg is reached	Used for chronic weight management in adult patients	May impact the absorption of medications
Rybelsus (semaglutide)	7 mg or 14 mg tablet once daily	Taken as a pill by mouth; no need for injection or refrigeration	Has to be taken with no more than 4 oz. of water on an empty stomach; has to be taken daily vs. weekly for the injected version

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 to 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.

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 the proper disposal of these supplies.

Side Effects

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

Common Side Effects

These include nausea, vomiting, and diarrhea, which affect 10% to 40% of people who take a GLP-1 receptor agonist.

Side effects 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 can also 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 vomiting
Skin rash or hives
Itching
Pounding heart
Dizziness or fainting
Swelling of the eyes, face, mouth, tongue, throat, feet, ankles, or lower legs
Trouble swallowing or breathing
Hoarseness
Decreased urination
Very dry mouth or skin
Extreme thirst
Ileus

The FDA approved updates post-marketing label of Ozempic to note the potential increased risk of intestinal blockage. The condition, called ileus, occurs when there are problems pushing food through the intestine and can cause build-up and blockage there. The weight loss drug Wegovy, which has the same active ingredient as Ozempic, and the diabetes drugs Rybelsus and Mounjaro have listed ileus on their safety labels.

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.

Summary

GLP-1 agonists like Byetta, Trulicity, and Ozempic treat type 2 diabetes and promote weight loss.

These injectable diabetes medicines are incretin mimetics and help to control appetite and blood sugar, slow digestion, and prompt the pancreas to release insulin.

GLP-1 side effects are usually mild and include nausea, vomiting, diarrhea, and headache. More serious side effects, including ongoing abdominal or allergic reactions, should be treated as an emergency.

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7 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

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By Barbie Cervoni, RD
Cervoni is a New York-based registered dietitian and certified diabetes care and education specialist.

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