What are GLP-1 receptor agonists, and how do they work?

It can be tricky to find effective ways to manage type 2 diabetes and blood sugar levels. Often, it requires multiple medication and lifestyle changes to keep your blood sugar under control. 

Fortunately, there are a few different types of medications that may help, including GLP-1 receptor agonists. GLP-1 receptor agonists are a type of non-insulin medication that may help control blood glucose and may even help you lose weight. 

Keep reading to learn more about what GLP-1 agonists are, their benefits, and potential side effects.  

Glucagon-like peptide-1 receptor agonists (GLP-1 RA), also called GLP-1 agonists, are a class of drugs used to treat type 2 diabetes mellitus. A small number of GLP-1 agonists are also FDA-approved to treat obesity.

GLP-1 receptor agonists work by mimicking the effects of the hormone glucagon-like peptide to regulate appetite and blood glucose levels. GLP-1 is a type of incretin hormone, meaning it’s created in the gut and released after eating a meal. 

It helps to lower blood sugar by:

• Increasing insulin secretion: GLP-1 stimulates the beta cells in the pancreas to release more insulin, which helps lower blood sugar levels (Tran, 2017).

• Delaying gastric emptying: GLP-1 slows digestion and keeps food in the stomach longer. This helps keep you feeling full longer and may prevent blood sugar spikes (Tran, 2017).

• Preventing the liver from releasing stored glucose: GLP-1 lowers the secretion of glucagon, which is a hormone that helps bring glucose out of storage and into the bloodstream (Liu, 2019).

GLP-1 agonists are either short- or long-acting medications, depending on how long their effects last.

Short-acting GLP-1 receptor agonists

Short-acting GLP-1 agonists stay in your body for up to a day, so they’re typically taken once or twice a day (Hinnen, 2017). 

Examples of short-acting GLP-1 agonists approved by the Food and Drug Administration (FDA) are:

• Exenatide (Byetta)

• Liraglutide (Victoza, Saxenda)

• Lixisenatide (Adlyxin)

• Oral semaglutide  (Rybelsus)

• Exendin-4

Long-acting GLP-1 receptor agonists

Long-acting GLP-1 agonists stay in your body for up to a week after you take them, so they’re usually given once a week. FDA approved long-acting GLP-1 receptor agonists include:

• Exenatide extended-release (Bydureon)

• Dulaglutide (Trulicity)

• Semaglutide (Ozempic, see Important Safety Information; Wegovy, see Important Safety Information)

You typically inject most forms of GLP-1 receptor agonists into the skin of the upper arm, thigh, or stomach. This is called “subcutaneous injection.” Only oral semaglutide is available as a pill. 

The injectable GLP-1 medications arrive in a disposable pen injection device. These usually come as one-time-use pens. But with other varieties, you’ll have to measure the medication and fill the injectable pen yourself. 

The devices come with a very small needle for administering the medication. They’re designed this way to keep them easy to use while causing minimal discomfort. 

Always follow your healthcare provider or pharmacist’s recommendations for how often to take your medications. Short-acting GLP-1 receptor agonists will be prescribed once or twice daily. Long-acting versions are usually recommended once per week (Uccellatore, 2015). 

When you start taking these medications, your healthcare provider will likely start you at a low dose. Then they’ll likely slowly increase your dose, depending on your blood sugar levels.

GLP-1 receptor agonists are primarily prescribed to help control type 2 diabetes because they help manage blood glucose levels. And research suggests they may have a few other health benefits, including:

Helping weight loss and healthy weight maintenance

These medications have been shown to help people lose weight and lower the risk of obesity-related complications. In fact, studies show that GLP-1 receptor agonists may help people maintain an average weight loss of up to 17% of their initial body weight (Rubino, 2021). 

While the exact connection between GLP-1 receptor agonists and weight loss isn’t clear, there are a few ways they likely work.

One important factor may be that GLP-1 receptor agonists can cause delayed stomach emptying, which helps keep you full longer, increases satiety, and suppresses your appetite (Muller, 2019). Since an empty stomach is one of the cues for your brain to produce hunger signals to drive you to eat, the longer your stomach stays full after eating, the easier it is to avoid extra snacking. 

Another likely mechanism for weight loss is that GLP-1 receptor agonists talk directly to the areas of the brain in charge of feeling full and satisfied, helping you to feel full faster. The result is that you will likely consume fewer calories, ultimately leading to weight loss.

Lower risk of diabetes-related complications

Cell and tissue damage can occur when blood sugar levels remain high for long periods, leading to diabetes-related complications, like kidney, nerve, blood vessel, and eye problems.

The glucose-lowering effects and weight loss benefits of GLP-1 receptor agonists may help lower the risk of diabetes-related complications. 

However, the research is mixed. Some studies show these medications reduce the rates of complications like chronic kidney disease or nephropathy. Other research on retinopathy and other eye problems is mixed. Some research shows that these medications possibly increase the progression of retinopathy or eye problems, while other studies show that they might have a beneficial effect (Dicembrini, 2017).  

May improve heart health

Several GLP-1 medications appear to improve heart health and reduce the risk for cardiovascular events. Specifically, dulaglutide, liraglutide, and injectable semaglutide are associated with reduced cardiovascular risk (Trujillo, 2021). 

Early clinical trials suggest GLP-1 receptor agonists may lower cardiovascular disease risk by lowering blood pressure, improving cholesterol and lipid levels, and improving heart function (Uccellatore, 2015).

Slow the progression of kidney disease

Chronic kidney disease is a frequent complication of uncontrolled diabetes. Studies show GLP-1 agonists may help slow the progression of the disease and reduce the loss in kidney function (Greco, 2019). 

Overall, GLP-1 receptor agonists are considered safe and cause minimal side effects. When people experienced side effects in clinical trials, most side effects were mild and short-lived. Because of the effects GLP-1 agonists have on digestion, the most common side effects for these medications are gastrointestinal problems, like (Tran, 2017):

• Nausea

• Vomiting

• Constipation

• Diarrhea

• Bloating 

• Indigestion 

GLP-1 may worsen symptoms of severe gastroesophageal reflux (acid reflux or heartburn) and gastroparesis—a condition where the stomach doesn’t move food around as well and doesn’t fully empty (Hinnen, 2017). 

So, GLP-1 agonist medications could worsen the symptoms of gastroparesis by keeping food in the stomach even longer. And for people with acid reflux, food staying in the stomach longer could increase the number and severity of symptoms. 

Another potential side effect of GLP-1 agonists is a small risk for developing pancreatitis (inflammation of the pancreas) when taking liraglutide and dulaglutide (Tran, 2017).

Other potential side effects involve skin reactions at the injection site, such as redness, itching, rash, or hives.

Finally, a rare but serious side effect of GLP-1 receptor agonists is a potential risk for thyroid cancer. In animal studies, there appears to be a link between liraglutide and an increased risk for this type of cancer. However, this pattern hasn’t been seen in human clinical trials (Tran, 2017).

It’s common for a healthcare provider to prescribe GLP-1 receptor agonists in addition to other medications used to treat type 2 diabetes, such as Metformin or insulin. 

When you combine GLP-1 receptor agonists with other diabetes medications, there is an increased risk of developing low blood sugar (hypoglycemia). Signs of hypoglycemia include fatigue, shakiness, sweating, irritability, pale skin, confusion, and loss of consciousness.  

If you experience low blood sugar, the typical recommendation is to consume a sugary food or drink to raise your blood sugar levels—speak with your healthcare provider to help develop a plan if this happens. And if symptoms don’t improve after treating them, seek medical attention. 

And since GLP-1 receptor agonists slow digestion, it’s possible for them to affect how your body absorbs other medications, so be sure to mention all of the medications you’re currently taking to your healthcare provider. 

If you have more questions about GLP-1 receptor agonists and are wondering if you could benefit from adding one to your type 2 diabetes treatment plan, talk with your healthcare provider or pharmacist.

---

How we reviewed this article

Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the writer.

Editorial Guidelines | Medical Review Process

Current version

February 16, 2022

Written by

Ashley Braun, RD, MPH

Fact checked by

Steve Silvestro, MD

---

About the medical reviewer

Steve Silvestro, MD, Ro

Dr. Steve Silvestro is a board-certified pediatrician and Associate Director, Clinical Content & Education at Ro.