GLP-1 Agonists for Type 2 Diabetes

Injectable Medications That Lower Blood Sugar and Aid Weight Loss

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.

A woman checking her diabetes reader
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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.

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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.

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 levels
  • Help the pancreas release the optimal amount of insulin, which transports glucose (sugar) to tissues in the body where it can be used for energy
  • Slow 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.

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.

Short-acting GLP-1 Receptor Agonists
Name of drug 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 sometimes can 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 Saxendsa is indicated for weight loss. Often causes nausea Saxenda is only covered by certain insurance providers.
Adlyxin (lixisenatide) 10 mcg daily the first two weeks, increasing to 20 mcg dailyn thereafter Has relatively the same efficacy as Byetta. Must be dosed daily 60 minutes before the first meal of the day Is excreted via the kidneys; shouldnot be used by people with low GFRs 
Long-acting GLP-1 Receptor Agonists
Name of medication 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 percent. Pen can be hard to use and causes a grape-sized ball on the skin.
Trulicity (dulaglitide) 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 percent
Ozempic (semaglutide) 0.25 mg the first four weeks; 0.5 mg thereafter. If after 4 weeks more blood sugar control is needed, 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 Reduces A1C by as much as 1.8 percent
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 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 on 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 into your upper arm.

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

  1. 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.
  2. Gather your supplies: an alcohol pad, bandage, gauze, or tissue, and your prepared or mixed medication in a pen or vial and syringe.
  3. Wash your hands.
  4. 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.
  5. Draw up your correct dose, either in the prefilled pen or syringe.
  6. Take a large pinch of skin and pull it away from the muscle underneath.
  7. Holding the pen or syringe like a dart, quickly insert the needle at a 90-degree angle to the skin.
  8. Slowly inject the medication.
  9. Release the skin, then withdraw the needle.
  10. 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 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 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 vomiting
  • A 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

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.

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