GLP-1 agonists

Diabetes and obesity are two of the most impactful disorders on the health of Americans. The American Diabetes Association estimates that almost 12% of the U.S. population has diabetes and according to the Centers for Disease Control and Prevention (CDC) over 40% are considered obese.

For some people, lifestyle changes such as eating a reduced-calorie diet and regular exercise are enough to manage their condition. For others, they may also need medications. One group of drugs that is used to treat diabetes and obesity is glucagon-like peptide-1 (GLP-1) receptor agonists. These are relatively new medications. The U.S. Food and Drug Administration (FDA) approved the first GLP-1 agonist (exenatide) in 2005. They are most often injectable medications, although some canf be taken by mouth. GLP-1 medications can be given anywhere from once or twice daily to once weekly, depending on the specific drug.

While they have become extremely popular in the last few years, these medications are not for everyone. Read on and get a better understanding of GLP-1 drugs and talk with your healthcare provider to see if one is right for you.

Glucagon-like peptide-1 receptor agonists, also known as GLP-1 agonists, GLP-1 receptor agonists, GLP-1 RA’s, incretin mimetics, or GLP-1 analogs, are a class of medications used along with diet and exercise in the treatment of type 2 diabetes mellitus (T2DM) and obesity. They mimic (copy) the GLP-1 hormone naturally released in your gastrointestinal (GI) tract in response to food. This hormone lowers your blood sugar levels and can help you eat less and lose weight.

When eating, your digestive system breaks down carbohydrates into simple sugars that enter your bloodstream. In response to this, your body releases the incretin hormone GLP-1. It stimulates insulin secretion from your pancreas, blocks the release of glucagon, slows stomach emptying, and helps you feel full longer.

If you have type 2 diabetes (T2DM), your body's cells don’t use insulin properly, your pancreas does not make enough insulin, or both. GLP-1 receptor agonists’ main mechanism of action is they stimulate your pancreas to make more insulin and inhibit the secretion of glucagon. Insulin helps take sugar (glucose) out of your bloodstream and into your body’s cells where it is used for nutrients and energy. Glucagon is responsible for triggering the release of stored glucose by your liver. Both of these actions help lower blood glucose levels in type 2 diabetics.

GLP-1 receptor agonists also act in your brain to decrease hunger and slow down gastric emptying (the speed at which your stomach empties). This can make you feel full for a longer period of time (satiety), which can help reduce your food intake and lose weight. In the past few years, several GLP-1 receptor agonists have been approved by the FDA for weight loss in obese people who don’t have type 2 diabetes. When used for obesity, these medications are usually given in higher doses than when given for type 2 diabetes.

Several types of GLP-1 medications are FDA-approved along with diet and exercise to treat either type 2 diabetes or obesity. Examples include:

Short-acting GLP-1 agonist injections

-Byetta (exenatide): This type 2 diabetes medication is given as a subcutaneous injection (under the skin) twice daily.

-Victoza (liraglutide): This type 2 diabetes medication is given as a subcutaneous injection (under the skin) once daily.

-Saxenda (liraglutide): This weight loss drug is given as a subcutaneous injection (under the skin) once daily.

-Adlyxin (lixisenatide): This type 2 diabetes medication is given as a subcutaneous injection (under the skin) once daily. It is no longer -available in the United States.

Long-acting GLP-1 agonist injections

-Ozempic (semaglutide): This is a once-weekly subcutaneous injection (under the skin) that is used to treat type 2 diabetes.

-Wegovy (semaglutide): This is a once-weekly subcutaneous injection (under the skin) that is used to help you lose weight.

-Bydureon Bcise (exenatide extended-release): This is a once-weekly subcutaneous injection (under the skin) that is used to treat type 2 diabetes.

-Trulicity (dulaglutide): This once-weekly subcutaneous injection (under the skin) is used to treat type 2 diabetes.

Oral GLP-1 agonist

-Rybelsus (semaglutide): This is the only oral GLP-1 receptor agonist currently available. It is taken once daily to treat type 2 diabetes.

There is also a similar class of drugs called dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. There is currently one of these medications available called tirzepatide. It is marketed as a type 2 diabetes medication with the brand name Mounjaro and as a weight loss drug known as Zepbound.

There are GLP-1 receptor agonists available that are approved to treat either type 2 diabetes or obesity along with lifestyle interventions (reduced-calorie diet and exercise).

GLP-1 receptor agonists are typically given to help manage glucose control if you have type 2 diabetes and:

-Can’t take metformin

-Still have high blood sugar levels (hyperglycemia) or A1C levels while on other diabetes medications

-Are having complications related to:

-chronic kidney disease (CKD)

-heart failure

-atherosclerosis

These medications can also help reduce the risk of cardiovascular events such as heart attack, stroke, or death in adults with type 2 diabetes mellitus and known heart disease.

For weight loss, healthcare professionals may prescribe GLP-1 receptor agonists if you have a starting body mass index (BMI) of 30 or higher or if you have a BMI of 27 or higher and at least 1 weight-related health condition, including:

-Type 2 diabetes

-Cardiovascular disease (CVD) or have CVD risk factors

-High blood pressure (hypertension)

-High cholesterol

-Liver (hepatic) disease that is not due to alcohol

-Polycystic ovary syndrome

-Obstructive sleep apnea

The most common side effects of glucagon-like peptide 1 (GLP-1) agonists seen in clinical studies include nausea, vomiting, diarrhea, and loss of appetite. These are more likely to occur when you first start the medication or when you increase the dose. Some other possible side effects that may occur include:

-Headache

-Stomach pain

-Fatigue

-Constipation

-Dizziness

-Heartburn or indigestion

-Low blood sugar (hypoglycemia), especially if taken with insulin or a sulfonylurea

-Bloating

-Gas

-Mood changes

Although rare, they can rarely cause serious and sometimes life-threatening adverse effects such as:

-Severe allergic reaction

-Pancreatitis

-Gallstones

-Kidney problems

-Worsening vision (diabetic retinopathy) in type 2 diabetics

-Heart rate changes

-Suicidal thoughts or behaviors

-Increased risk of thyroid cancer

-Bowel obstruction (a blockage that keeps food from passing through your intestines)

These are not all of the possible adverse effects of these medications. You should always seek medical advice from your healthcare provider for any questions or concerns about your medical condition or treatment. Read all patient information, medication guides, or drug information sheets that come with your medication. You can also report adverse effects to the Food and Drug Administration at www.fda.gov/medwatch or 1-800-FDA-1088.

Although these medications are generally well-tolerated and safe, you should not take them if you:

-Are pregnant or plan on becoming pregnant.

-Have a history of pancreatitis or thyroid tumors

-Are allergic to the active ingredient or any inactive ingredients in the -drug’s formulation

-Have multiple endocrine neoplasia (MEN) syndrome type 2

It is important to discuss any other medications you are taking with your healthcare provider to be sure there are not any serious drug interactions.