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What are GLP-1 Receptor Agonists? And How Do They Treat Obesity?

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This class of prescription drugs—called 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 benefits are. We’ve got you covered. And we’ll give you the scoop on some other medications you might want to consider. So let’s get to it.

What are GLP-1 medications?

GLP-1 RAs are medications used to treat obesity and type 2 diabetes. They mimic a natural hormone in your gut that helps regulate weight, and they can be used to jumpstart and sustain weight management, especially when used alongside other methods. GLP-1 RAs help manage glucose levels—more commonly known as blood sugar, as well. Better blood sugar control can also improve weight care and provide a host of other health benefits.

“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, Found’s Chief Behavioral Health 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 medications work?

There are cells located in the gut, called L-cells, that produce a peptide hormone called GLP-1, which regulates appetite. GLP-1 RA meds are a synthetic version of this natural hormone. They delay stomach emptying, and send signals to thebrain’s hypothalamus that promote feelings of fullness and suppress hunger.

“When the drug makes me full,” Parks says, “I stop eating with no fanfare. It feels like I'm too full to go on eating. So there's nothing to miss 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 drug works. But it also helps manage blood sugar levels. In response to glucose, GLP-1 binds to the receptor of pancreatic cells that produces insulin, increasing its secretion. Insulin is a hormone that lowers blood sugar after a meal. Over time, high blood sugar levels make these cells work harder to secrete insulin, which can eventually lead to their dysfunction or to cell death. GLP-1 has a protective effect on insulin-secreting cells—and itreduces the production of glucose in the liver. Because of their ability to help manage blood sugar and control insulin, GLP-1 RAs first became a popular treatment for type 2 diabetes.

Why take diabetes drugs for weight care?

Because clinicians noticed that people taking GLP-1 RAs also experienced weight-loss. That’s when researchers began studying the drugs and found they could help with weight management.

People with obesity secrete less GLP-1, according to research published in the World Journal of Diabetes.After weight loss, however, production of this hormone is increased. What that means is that underlying biological processes may be hindering your weight care progress. GLP-1 RAs can remove an obstacle so you can reach your goals.

In fact, in a clinical trial published in the New England Journal of Medicine, participants with excess weight or obesity taking Wegovy—the brand name for the GLP-1 RA semaglutide—lost an average of almost 15 percent of their body weight over the course of 68 weeks, compared to those given a placebo (who shed just over 2 percent).

Even in the absence of diabetes, GLP-1 RAs can be beneficial for metabolic health—by supplementing the natural hormone GLP-1. It encourages the body to use energy more efficiently and promotes insulin sensitivity. Both are beneficial to weight care.

As we mentioned before, 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 the journal BMJ Open Diabetes Research and Care.This bidirectional relationship is another example why 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,” Parks adds, “I was prescribed metformin, which is a diabetes drug, even though I don't have diabetes. 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 RAs?

Yes. GLP-1 RAs have been shown to reduce the risk of heart attack and stroke, or death from cardiovascular issues, and to lower blood pressure, according to a review of studies published in BMJ Open. These meds may also help prevent a decline in kidney health among those with moderate to severe kidney disease, according to recent research published in The Lancet Diabetes & Endocrinology.

What are the side effects of GLP-1 medications?

Not everyone experiences side effects on a GLP-1 RA. When they do occur, they tend to be minor in nature, and include symptoms such as nausea, vomiting, and diarrhea. Headaches and upper respiratory congestion may also occur. Some of these medications are administered as a shot, and you may experience tenderness or redness at the injection site. Serious side effects of GLP-1 RAs are rare, but may include an allergic reaction or abdominal pain.

What’s it like to take a GLP-1?

Recently Parks experienced a vacation full of all-you-can-eat options, and she could see how her GLP-1 helped her maintain her continued pound-a-week weight loss, even though she says she would have normally gained on such an adventure. We’ve heard similar feedback from other members taking GLP-1s, but everyone’s experience is different.

“It has dramatically changed my relationship with food,” she explains. “I eat it to keep my body going, but it doesn't give me the same emotional high that it used to.”

Instead, GLP-1s have given her the freedom to indulge elsewhere. “I now have to build other sources of joy in my life where I used to get it from food—areas I have been neglecting, by the way, because food was filling such a huge hole in my life,” Parks adds. “It's a good problem to have.”

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

They’re dual agonists—which means that a medication will activate both GLP-1 and GIP. GIP stands for gastric inhibitory polypeptide.

Like GLP-1, GIP is another natural gut hormone. It makes you feel full and satisfied after eating, improves insulin sensitivity, increases the number of insulin-secreting cells in the body, and helps manage fat storage. GIP can be reduced in people with insulin resistance and obesity. Activating GIP bolsters that activity, as noted in a study published in Trends in Endocrinology and Metabolism. And when GIP and GLP-1 activation occur together in a medication (GIP/GLP-1), research in the journal Lancet shows some great weight care results.

One 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 up to 22 percent of their body weight while on the medication over the course of 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 are ecstatic that GIP/GLP-1s may be even more of a game-changer for weight care.

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

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

Depending on the medication prescribed, GLP-1 RAs are taken either orally or as an 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.

What is ‘off-label’ prescribing?

The FDA approved Mounjaro for blood sugar control in patients with type 2 diabetes. Sometimes physicians prescribe medications off-label when they know, based on clinical evidence, that a drug is beneficial for a reason it’s not yet approved for. For example, anticonvulsant medications, typically approved to prevent seizures, have been prescribed off-label for decades for fending off migraines.

Is off-label prescribing safe?

Generally, yes. Take the case of Monjouro, which was studied in people with type 2 diabetes, many of whom also had obesity. “What's really amazing about that,” Parks explains, “is being able to capitalize on clinical trials that have already happened and that assessed weight loss as a secondary variable. Imagine if we had to wait for those clinical trials to run all over again before we could start helping people!”


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 the management 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 of 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, and 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 or another prescription weight care med is right for you.

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