GLP-1 Agonists for Type 2 Diabetes

Injectable Medications That Lower Blood Sugar and Aid Weight Loss

A woman injecting a GLP-1 agonist
fertnig/istock 

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. The specific role of these drugs is to to help lower blood glucose levels—specifically, hemoglobin A1C—and to aid in weight loss. Research has shown that GLP-1 receptor agonists can have other health benefits, including positive effects on blood pressure, cholesterol levels, and beta-cell function.

These injectable drugs are prescribed along with oral diabetes medicines and insulin therapy. As such, they aren't regarded as first-line diabetes drugs, but they can be a valuable part of treatment with relatively few side effects.

How They Work

GLP-1 stands for glucagon-like peptide, a type of hormone known as an incretin hormone 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 that help the pancreas to release the optimal amount of insulin, a hormone that transports glucose (sugar) to tissues in the body where it can be used for energy.

These drugs also slow the rate at which food leaves the stomach, which helps to control post prandial (after meal) blood sugar levels.

By mimicking the following effects of GLP-1 on several parts of the body, GLP-1 receptor agonists help to control appetite and blood sugar levels:

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—an effect that can lead to weight loss.

Dehydration Danger


Because GLP-1 receptor agonists dampen the sensation of the need to drink, it's vital to take special care to drink plenty of water and other fluids in order to stay hydrated while on such a medication.

Muscle

GLP-1 stimulates gluconeogenesis—the synthesis of glucose in the body. More simply, it's the conversion of protein or fat (rather than carbohydrates) to sugar for the body to use as fuel in the muscle. An increase in this process can help to lower blood sugars by stimulating glucose uptake by the cells and increasing how efficiently the body uses insulin.

Pancreas

When GLP-1 comes in contact with glucose, the pancreas is triggered to secrete more insulin, thereby lowering the amount of post-meal glycogen in the blood. GLP-1 also decreases the secretion of glucagon—a 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 to lower blood sugars. 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 that in turn can limit how much a person eats and 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 typically is based on a number of factors, including medical history, insurance coverage, and price (GLP-1 receptor agonists can be expensive), personal preference, and effectiveness of blood sugar control.

Short-acting GLP-1 Receptor Agonists
Name of drug Dose Pros Cons Other considerations
Byetta (exenatide) 0.5 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

Proven to promote the most weight loss

Associated with a high incidence of nausea  Nausea caused by liraglutide may be a contributing factor to weight loss
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
 
Trulicity (dulaglitide) 0.75 mg weekly; increase to 1.5 mg after 6 to 8 weeks. Comes as a pre-filled pen 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. Comes as a pre-filled pen As a newer drug, can be pricey Reduces A1C by as much as 1.8 percent

Administration

All 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 doctor prescribes a GLP-1 receptor agonist, he or she will go over the steps for 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 pens should be discarded after 30 days, even if there is some solution left inside.

Side Effects and Complications

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 pain in the upper left or middle of the stomach that may spread to the back, 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

Effective treatment for type 2 diabetes is a subject of robust research. There is a great deal of interest in developing better and better medications, including safer, more convenient, and more effective GLP-1 receptor agonists. In fact, one such option, an oral form of semaglutide, is being considered for approval by the U.S. Food and Drug Administration. Not only does this version of the drug help control blood sugar levels, but it has also been shown to reduce heart risks—a bonus benefit of a drug that may one day be taken as a pill rather than with a needle.

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