What are GLP-1s and how do they treat obesity?

This class of prescription medications—glucagon-like peptide 1 receptor agonists (GLP-1 RAs)—has generated a lot of buzz for their ability to help with weight care. So it’s no wonder you’re curious to learn more about how they work and what the weight care benefits may be. We’ve got you covered. And we’ll give you the scoop on other medications you might want to consider. So let’s get to it.

What is a GLP-1 agonist?

GLP-1 RAs (or GLP-1s for short) are medications used to treat type 2 diabetes and obesity. They mimic a natural hormone in your gut that helps regulate weight. GLP-1 agonists help manage glucose levels—blood sugar–in the treatment of diabetes and lower weight. As such, you can also use them to jumpstart and sustain weight management, especially when used alongside other methods.

“For me, the experience of using a GLP-1 has been like systematically peeling away behavior patterns that I thought were part of me, part of my personality,” says Acacia Parks, PhD, Found’s Fractional Chief Science Officer. “They were actually hormonal signals insisting, begging me not to weigh less than my body thought I should. To my body, my life was at stake, and I was starving. It was throwing everything at me that it could to make it difficult for me to be thin.”

How do GLP-1 agonists work?

Some cells in the gut, called L-cells, produce a hormone called glucagon-like peptide 1 (GLP-1), which helps regulate appetite. GLP-1 agonist meds are a synthetic version of this natural incretin hormone. They delay stomach emptying and send signals to the brain’s hypothalamus that promote feelings of fullness and suppress hunger.

“When the drug makes me full, I stop eating with no fanfare,” says Parks. “ It feels like I'm too full to go on eating. So there's nothing to mess with the food I left behind. I don't wish I was eating it. I don't want it at all.”

That’s one way the medication works. But it also helps manage blood sugar levels. GLP-1 binds to pancreatic cell receptors that produce insulin in response to glucose, increasing secretion. 

Insulin is a hormone that helps lower blood sugar after a meal. Over time, high blood sugar levels make these cells work harder to release insulin, which can eventually lead to dysfunction or cell loss. 

GLP-1 has a protective effect on these insulin-secreting cells—and inhibits glucose production in the liver. Because of their ability to help manage blood sugar and control insulin, GLP-1 agonists became a popular treatment for diabetic patients—before they were used for weight care.

What drugs are GLP-1 agonists?

Health care providers prescribe a number of GLP-1 agonists weight loss or type 2 diabetes. Some of the most popular GLP-1 RAs that you’ve most likely heard of as treatment options are:

• Trulicity® (dulaglutide)

• Victoza® (liraglutide)

• Ozempic® (semaglutide)

• Saxenda® (liraglutide)

• Byetta® (exenatide)

• Bydureon BCise® (exenatide)

• Rybelsus® (oral semaglutide)

• Wegovy® (semaglutide)

Why take a diabetes drug for weight care?

The short answer is that clinicians noticed that people taking GLP-1 agonists also experienced weight loss. That’s when researchers began studying the drugs and found they could prescribe them off-label to help with weight management. 

According to research published in 2015 in the World Journal of Diabetes, people with obesity can secrete less GLP-1. Unfortunately, this means your biology may hinder your weight loss. GLP-1 RAs can help you reach your goals by slowing the time it takes for food to move from your stomach, leading to increased satiety and decreased appetite. 

In fact, in a double-blind clinical trial published in 2021 in The New England Journal of Medicine, participants with excess weight or obesity taking semaglutide—a GLP-1 agonist—lost an average of almost 15% of their body weight over 68 weeks compared to those given a placebo (who dropped just over 2% of their body weight). 

Even in the absence of diabetes, GLP-1 RAs can benefit metabolic health by encouraging the body to use energy more efficiently and promoting insulin sensitivity. Both can be significant pluses for weight care.

As we mentioned, high blood sugar can lead to insulin resistance (the opposite of insulin sensitivity). Obesity and insulin resistance are linked, with each driving the other, according to a study published in 2020 in the journal BMJ Open Diabetes Research & Care. This bidirectional relationship is another reason biological processes can make weight care so complex. 

“As someone who has struggled with obesity for my whole life and who saw type 2 diabetes as something inevitable, it was an ‘aha!’ moment for me to realize that the mechanisms that lead to obesity and the mechanisms that lead to type 2 diabetes have quite a lot of overlap!” says Parks.

“When I started my own medication-supported weight loss journey last year, I was prescribed metformin, which is a diabetes drug, even though I don't have diabetes,” says Parks.” I took it, and lo and behold; it disabled one of the major signals in my body that kept me overweight: a craving for sugar. Of course, sugar is central to diabetes as well. So it's no surprise that medications that target GLP-1 are highly efficacious for weight loss, even though they were originally developed for diabetes.”

Are there any other benefits of GLP-1 agonists?

Yes. GLP-1 RAs reduced the risk of heart attack and stroke or death from cardiovascular events in patients with type 2 diabetes, according to a review of studies published in the Postgraduate Medical Journal. In another study, it also lowered blood pressure. On top of that, your risk of cardiovascular outcomes if you have heart disease is reduced. They can also help prevent heart failure.

Moreover, GLP-1 RAs can help regulate cholesterol in patients with type 2 diabetes, according to Current Diabetes Reviews. And research published in The Lancet Diabetes & Endocrinology found that these meds may also help prevent a decline in kidney health among those with moderate to severe kidney disease.

What are the side effects of GLP-1 drugs?

Not everyone experiences side effects on a GLP-1 RA. When they occur, they tend to be minor and include symptoms such as nausea, vomiting, gastrointestinal issues, and diarrhea. Headaches and upper respiratory congestion may also occur. 

You will administer some of these medications as a shot and may experience tenderness or redness at the injection site. 

Serious side effects of GLP-1 RAs are rare. Still, they may include a severe allergic reaction, a drop in blood glucose levels (hypoglycemia), thyroid tumors, or severe abdominal pain.

How much does a GLP-1 agonist cost?

That’s a great question. The cost of GLP-1 RAs varies and depends on what the health care provider prescribes them for and if your insurance covers them. 

Let’s back up for just a second. Most insurance companies cover GLP-1 agonist meds developed for the treatment of type 2 diabetes–but often prescribed off-label for overweight and obesity–if the health care provider prescribes them for their indicated use. 

However, insurance typically does not cover Saxenda and Wegovy because they’re classified as obesity drugs. In fact, most insurance companies still need to catch up on the realization that obesity is a disease, and they need to cover these drugs to help treat the chronic condition.

According to Novo Nordisk, the Danish pharmaceutical company that manufactures Saxenda, the list price currently is $1,349.02 for a 30-day supply. They have a savings card through NovoCare, but you must meet certain conditions for qualification.

Following that, Wegovy, also manufactured by Novo Nordisk has the same list price as Saxenda—$1,349.02 per 28-day supply—as of March 2023. Consider that Saxenda is a 30-day supply because you'll inject it daily, whereas Wegovy is a once-weekly long-acting weight-loss shot. 

The cost of other drugs in the GLP-1 agonist group vary greatly depending on your insurance. Out-of-pocket costs can be as low as $25 per fill depending on your insurance coverage if the health care provider prescribes them for type 2 diabetes. 

If you have type 2 diabetes and are overweight or obese, you may be able to try GLP-1 RAs for your diabetes care and lose weight concurrently.

What are GIP/GLP-1 medications—and how are they different from GLP-1?

It is a gastric inhibitory polypeptide (GIP) and GLP-1 agonist that activates both GLP-1 and GIP receptors, making it a dual receptor co-agonist..  

Like GLP-1, GIP is another natural gut hormone. It helps you feel full and satisfied after eating, improves insulin sensitivity, increases the activity of insulin-secreting cells in the body, and helps manage fat storage. 

People with insulin resistance and obesity can have lower GIP. Activating GIP bolsters that activity, as noted in a Trends in Endocrinology & Metabolism study. And when GIP and GLP-1 activation occur together in a medication (GIP/GLP-1), the results of a double-blind, randomized phase three trial published in the journal The Lancet shows some great weight care results.

One diabetes medication obesity doctors are excited about is Mounjaro®—the brand name for the GIP/GLP-1 tirzepatide. It received Food and Drug Administration (FDA) approval in May 2022. 

In a trial among patients with type 2 diabetes—many of whom also had obesity—participants lost between 15 and almost 21 pounds of body weight while on the medication over 40 weeks. The results indicate that, although a GLP-1 is quite effective, a GIP/GLP-1 may offer even more benefits with its dual action. Since the results of GLP-1 meds have been so exciting, obesity doctors believe that GIP/GLP-1s may be a game-changer for weight care.

“While it is always possible that we will see more innovations, for now, medications like Mounjaro are certainly the cutting edge in obesity care,” explains Parks.

How are GLP-1 agonist and GLP-1/GIP medications taken?

Depending on the medication prescribed, patients take GLP-1 RAs orally or as a subcutaneous (under-the-skin) injection. For injectable versions, you give yourself a daily or weekly shot just under the skin at home. Oral medications involve taking a pill once a day. 

Note: GLP-1 agonist drugs are meant for those with type 2 diabetes mellitus and not to treat those with type 1 diabetes.

What is the most effective GLP-1 agonist for weight loss?

It depends on you and what drug works best for you. In clinical trials, some may be more effective for weight loss, but you may experience more side effects. Talk to your health care provider about the best drugs for you and be your advocate when you feel like a different drug may work better.

With that said, only two GLP-1 RAs have U.S. Food and Drug Administration approval for weight loss: Saxenda (liraglutide) and Wegovy (semaglutide). The FDA approved Saxenda for weight loss in 2014 and Wegovy for weight loss in June 2021. Both drugs have shown significant weight loss results in clinical trials. The results of one randomized clinical trial published in 2022 in JAMA had some interesting insight.

Indeed, when comparing the use of the GLP-1 RAs liraglutide and semaglutide for weight loss, those in the semaglutide group achieved, on average,  an almost 9 percent greater weight loss than the liraglutide participants. This suggests that semaglutide is the most effective FDA-approved weight-loss drug. But, as we mentioned, what works for one person may work differently for another, so trying various GLP-1 agonist options until you find the best fit for you may be the way to go. 

On top of that, we must mention Mounjaro when talking about the most effective weight loss drug. Although it’s in its own drug class, its weight loss results are outstanding. It essentially beat those in the GLP-1 agonist class by a landslide.

Takeaway

GLP-1 and GIP/GLP-1 medications mimic natural gut hormones that help curb appetite, make you feel fuller longer, and slow gastric emptying. These hormones also play crucial roles in managing of blood sugar and insulin. Of course, no pill or injection is a magic solution. But if you produce less GLP-1, a synthetic version that mimics the hormone may help with weight management. And GIP and GLP-1 receptor agonists work well together for even more benefit. Weight care is complex; sometimes, medication can make a big difference as an add-on to other management therapies and methods.

Work with one of Found’s board-certified medical providers to see if a GLP-1, a GIP/GLP-1 or another prescription weight care med is right for you. To start your journey with Found, take our quiz. 

GLP-1*

GLP-1 prescriptions, filled through your local pharmacy, are now available as part of Found's weight-loss toolkit. While GLP-1s are effective for weight loss, they are not clinically appropriate for everyone. Eligibility for a GLP-1 is based on a thorough evaluation of your medical history, eating behavior, lab work, and insurance coverage. If a GLP-1 is not appropriate for you, our providers will work with you to determine an effective medication for your health profile.

About Found

Found is among the largest medically-supported weight care clinics in the country, serving more than 200,000 members to date. To start your journey with Found, take our quiz.