How Do GLP-1 Receptor Agonists Work?

Weight loss: we love to see it, but we don't always love what we must do to achieve it. It is an ongoing journey that requires dedication, mindfulness, and making the right lifestyle changes. And even with all those things in play, many still find themselves on the weight loss struggle bus, or perpetually yo-yo dieting.

This difficulty has not gone unnoticed and, as a result, there has been a boom in approved prescription medications to help boost weight loss and support blood sugar metabolism to promote overall health.

Enter glucagon-like peptide 1 (GLP-1) receptor agonists, or GLP-1 RAs. This class of medications includes semaglutide (Ozempic® and Wegovy®) and tirzepatide (Mounjaro® and Zepbound®), among others. Everyone from Hollywood celebrities to your suddenly-slim next-door neighbor seem to be singing their praises, gleefully sharing before-and-after photographs.

But before you jump on the bandwagon, you probably have some questions. Such as: How do GLP-1 receptor agonists work? Are they right for you? What are the side effects, and can they be mitigated? And, are there other ways to address your GLP-1 receptors that don't involve medications?

We'll cover both the basics and the details so you can speak to your healthcare provider and decide the best approach for you.

What are GLP-1 receptors?

FDA approved weight loss medications that are GLP-1 receptor agonists behave much like the actual GLP-1 hormone in your body, which helps regulate your blood sugar and keep you satisfied from a meal, so you won't be hungry or crave second helpings.

So, how do GLP-1 receptors work? Well, it all starts with food. After you eat a meal, the L-cells in your intestines release the glucagon-like peptide 1 (GLP-1) hormone. The GLP-1 hormone then activates GLP-1 receptors, which play a role in digestion and glucose metabolism, including regulating blood sugar levels and feelings of fullness. GLP-1 receptors are expressed primarily by cells in the pancreas, but also in the nervous system, lungs, kidneys and other organs.

The effects of GLP-1 in the body can be described as four primary mechanisms:

1. Blocking the secretion of the hormone that raises your glucose levels

   . Glucagon is a hormone that raises glucose levels in the body, but GLP-1 blocks this action.

2. Telling your body to make energy from the food you ate

   . GLP-1 triggers insulin release: insulin tells your cells to take up glucose (sugar) from the blood to make energy.

3. Slowing digestion

   . Slower digestion means you feel fuller longer and your body releases less glucose into the blood.

4. Increasing satiety and decreasing appetite

   . Slower digestion means food stays around longer, so you feel fuller for longer. GLP-1 also affects areas of the brain that regulate hunger, decreasing overall appetite.

GLP-1 receptor agonist medications act like the GLP-1 hormone and have these four attributes, and for those reasons can reduce appetite, promote weight loss, and regulate insulin and blood sugar levels, just like the real GLP-1 hormone in your body.

What are the GLP-1 receptor agonist medications?

GLP-1 RAs like exenatide, tirzepatide, and semaglutide are prescription medications that have been approved by the FDA for the treatment of both type 2 diabetes and weight loss. Many GLP-1 drugs come as injectables that are injected just under the skin (subcutaneous), although some exist as oral formulations.

There are many different GLP-1 RAs available:

• Dulaglutide (Trulicity®)
• Semaglutide injection (Ozempic® and Wegovy®)
• Semaglutide tablets (Rybelsus®)
• Exenatide (Byetta®)
• Exenatide extended-release (Bydureon®)
• Liraglutide (Victoza®)
• Lixisenatide (Adlyxin®)
• Tirzepatide (Mounjaro® and Zepbound®)

How do GLP-1 RAs work?

GLP-1 RAs work by mimicking the effects of GLP-1 to lower blood sugar and decrease appetite. They do this by binding to and activating the GLP-1 receptor to cause the same effect as natural GLP-1. Think of it as having a second key to the same lock: one made by our bodies, one manufactured synthetically.

GLP-1 RAs can also indirectly promote healthy cardiovascular function and liver health due to the associated metabolic benefits and weight loss.

These medications fall under the class of incretin mimetics, meaning they mimic the effects of the incretin hormones which play a role in regulating digestion and glucose metabolism. The two main incretin hormones are glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide (GIP), which are secreted by the gastrointestinal tract after a meal.

What are the side effects of GLP-1 medications?

While GLP-1 RAs may cause some side effects, most commonly diarrhea, vomiting, and nausea, these range from mild to moderate and can be lessened by reducing the dose. However, these side effects cause many individuals to discontinue the use of GLP-1 RAs, resulting in weight gain after discontinuation.

It is important to work with your healthcare provider to find the right dose that limits side effects. GLP-1 RAs can work well but must be used in conjunction with other strategies like regular exercise and a healthy diet.

4 ways to increase your GLP-1 hormone without medication

Whether it's because of side effects or because you're just not a fan of taking medication when lifestyle changes can improve your health, there are ways to influence your GLP-1 hormone activity that don't involve medicine. Although GLP-1 secretion is complexly controlled by the body, studies suggest changes to your diet and lifestyle could increase GLP-1 levels.

1. Eat foods that help increase GLP-1 levels

Foods trigger an increase in GLP-1, since GLP-1 is primarily released in response to a meal, so what you eat may make a difference. Think of the staples of a healthy diet; foods that help increase GLP-1 levels include those high in fiber, healthy fats, and protein since they trigger the release of GLP-1.

Eggs, particularly egg whites, have been shown to increase GLP-1 secretion. Other foods, such as nuts, avocado, and olive oil, also can help. Interestingly, eating vegetables before carbohydrates has been shown to be an effective strategy.

Another added benefit of eating these GLP-1 friendly foods is promoting weight loss, which itself has many additional benefits ranging from cardiovascular health to liver health, brain health and more.

2. Get enough exercise

Exercise is an important part of a healthy weight plan and has been associated with greater GLP-1 responses, contributing to improved blood sugar metabolism and satiety. (This is why if you were prescribed GLP-1 RAs, you likely were instructed to exercise regularly.)

3. Quality sleep

Getting quality sleep is important for many aspects of health, including supporting GLP-1 levels. Studies have identified that a lack of sleep can reduce GLP-1 production and secretion, which can contribute to overeating. If the importance of sleep wasn't evident, it should be now! Aim to get seven to nine hours of sleep each night; sticking to a sleep schedule and avoiding screen time before bed are two easy ways to help improve the quality of your sleep.

4. Take probiotics

Probiotics have been examined for their ability to support GLP-1 levels by positively affecting the gut microbiome. One preclinical study identified that resveratrol and probiotics can increase GLP-1 levels in a rat model of type 2 diabetes compared to control. While some additional evidence suggests that probiotics can increase GLP-1 levels both directly and indirectly, clinical evidence is lacking.

Overall, more clinical studies are required to identify nutrients that support your GLP-1 secretory responses. But your digestive system, and the rest of the body, would appreciate a bit of added support from nutrients like probiotics! All in all, living a healthy lifestyle and being mindful of your diet can naturally support your GLP-1 levels and promote weight loss.

How much protein and fiber should you take while on GLP-1 medications?

An often-discussed consideration for people who take GLP-1 RA medications is maintaining healthy nutrient intake despite decreased food consumption. Dietary recommendations for protein and fiber intake are unique for each person and depend on current eating habits (daily amount, diet, etc.) and overall health goals. But let's discuss some basic recommendations:

• Protein

  : Dietary protein contributes to satiety and healthy blood sugar, which benefits weight management, and a good range is consuming about 15-30% of your total calories as protein. Adequate protein intake is also important for maintaining muscle mass, which tends to decline with age. Protein powder supplements are an easy and effective way to increase daily dietary protein intake.

• Fiber

  : Fiber requirements are also individualized, where most people should aim to consume approximately 25-35 grams daily. Foods high in fiber can help increase GLP-1 levels and they also help people feel full, since they take longer to digest than foods low in fiber. If you aren't sure where to start, try replacing refined grain products like white bread with whole grain versions.

That being said, if you are taking a GLP-1 RA medication, it can be hard to hit these goals due to your reduced appetite. That's why choosing nutrient-dense foods is key: think nuts, fruits, and vegetables instead of chips or pastries. Not only do these have a better nutrient profile, but they're also better for your weight and overall health! It is important to fill in the gaps in your diet that are not being met by food alone, so make sure to work with your healthcare provider to determine individual goals and strategies.

Can you test your GLP-1 levels?

Yes, it is possible to test your GLP-1 levels! However, this is typically a test done at the direction of a healthcare provider. These tests can directly measure GLP-1 levels in the blood, and other tests can be used to monitor the effect of GLP-1 RA medications such as tests measuring kidney function or blood sugar markers. These do not directly measure GLP-1 but can help provide a picture of how the body is responding to these medications.

Another approach is a comprehensive weight loss panel to evaluate levels of thyroid hormones, insulin resistance and general health markers.

GLP-1 RAs: Not a magic bullet

GLP-1 RAs are groundbreaking and effective medications, but they are not magic. With proper treatment adherence, they can help significantly reduce body weight and improve various aspects of overall health. These must be used under the guidance and direction of a healthcare professional and alongside a healthy lifestyle with diet and exercise.

Speak to your doctor and work on a personalized plan to maximize the benefits and promote healthy aging. Cheers to longevity!

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