GLP-1s & Inflammation: Exploring Benefits Beyond Weight Loss

What Are GLP-1 Agonists and How Do They Work?

Glucagon-like peptide 1 (GLP-1) is a hormone that the body naturally produces in response to eating. GLP-1 is mostly released from the gut, although a small amount is produced by the brain.

This hormone works to increase feelings of fullness, slow down stomach emptying and regulate blood sugar levels.

GLP-1 receptor agonists are drugs that have a similar structure to GLP-1, so they can trick the body into thinking GLP-1 levels are high. These drugs have been used to treat type 2 diabetes mellitus for many years thanks to their ability to increase insulin secretion and improve blood sugar control.

More recently, GLP-1 agonists have gained popularity as weight loss drugs, including Ozempic, Wegovy, and Mounjaro. Their ability to slow down stomach emptying and reduce hunger cues makes them very effective for for people trying to lose weight. However, GLP-1 agonists may also have other positive effects on the body.

How GLP-1 Reduces Inflammation

GLP-1 is known to have antioxidant and anti-inflammatory properties. When GLP-1 binds to its receptor, it can reduce the body's inflammatory responses. This means inflammation in the heart, blood vessels, liver, gut, and even the brain may all be lower when GLP-1 levels are higher.

Some of this effect may be due to GLP-1's ability to regulate blood sugar levels by increasing insulin secretion. High blood sugar is linked to inflammation, so reducing blood glucose levels may help to improve local or systemic inflammation.

However, GLP-1 also seems to be able to regulate some of the immune cells responsible for inflammation and reduce the amount of proinflammatory cytokines they produce (chemical messengers that tell the body to respond by increasing inflammation).

As GLP-1 receptor agonists have similar properties to GLP-1, it makes sense that they can also reduce inflammation.

Anti-Inflammatory Effects of GLP-1 Agonists

Several studies have demonstrated the anti-inflammatory effects of GLP-1 agonists.

Exenatide and semaglutide have been shown to lower proinflammatory cytokine levels in laboratory experiments and animal studies. In a mouse model, semaglutide, liraglutide, dulaglutide, and exenatide were all found to lower inflammation levels in different tissues.

Most human trials of GLP-1 agonists have been done in individuals with type 2 diabetes. In different studies, liraglutide treatment and exenatide treatment significantly reduced markers of inflammation, including a general inflammatory marker known as C reactive protein that's measured via a blood test.

Studies in overweight individuals found that semaglutide reduced inflammation levels, but statistical analysis showed that this may partly have been down to participants losing weight. Tirzepatide has also been shown to reduce inflammation in fat tissue in mice.

Based on the evidence, GLP-1 agonists are being investigated as potential treatments for all kinds of inflammatory diseases, including Alzheimer's disease, Parkinson's disease, and bowel diseases like Crohn's and ulcerative colitis. The anti-inflammatory effects of these medications may also help individuals with kidney disease

Impact on Immune Cells and Inflammatory Pathways

We've already touched on several studies that suggest GLP-1 agonists reduce inflammation by affecting immune cells and the cytokines they release. This seems to be true in cell experiments in the laboratory, animal models, and in human trials.

Research suggests that GLP-1 agonists work on a variety of immune cells known as macrophages. Macrophages are a type of white blood cell that work to neutralise threats by engulfing and destroying them. Usually, threats include things like bacteria, viruses, fungi, and dead cells.

Macrophages are grouped into two types: M1 and M2. M1 macrophages are proinflammatory, which means they're associated with increased levels of inflammation and help to destroy microbes and malfunctioning cells. M2 macrophages are anti-inflammatory and their role is in repairing damaged tissue. GLP-1 agonists may help to reduce the amount of M1 macrophages and increase the activity of M2 macrophages, leading to less inflammation.

GLP-1 agonists may also reduce levels of other pro-inflammatory immune cells, like T cells.

Some specific pathways, cells, and cytokines have been investigated, but research is still ongoing to fully understand how GLP-1 protects various tissues from inflammatory damage.

Common GLP-1 Agonists and Their Uses

Although GLP-1 agonists may have other uses in the future, currently, they're licensed for one of two reasons: type 2 diabetes or weight loss.

Initially, these medications were only licensed for glycaemic control in people with type 2 diabetes. However, researchers quickly realised that people taking these drugs for their diabetes were also losing a significant amount of weight. Often, people lose more weight with GLP-1 agonists than with other diabetes medications like metformin.

Currently in the UK, liraglutide, semaglutide, and tirzepatide are licensed for weight loss. Liraglutide may be found under the brand name Saxenda, semaglutide as Ozempic or Wegovy, and tirzepatide as Mounjaro. In the UK, Ozempic is licensed for diabetes management and Wegovy for weight loss, but some doctors choose to prescribe Ozempic off-label for weight loss.

Six types of GLP-1 agonists are licensed for the management of type 2 diabetes:

• exenatide

• liraglutide

• lixisenatide

• dulaglutide

• semaglutide

• tirzepatide

All six are injectable medications, but dosing depends on what you're taking the medication for and how long you've been taking it. Some of these medications are injected as often as twice daily, while others are taken once a week.

As with any medication, GLP-1 receptor agonists can cause side effects. Some of the possible side effects of these medications include:

• Stomach and intestinal issues - taste changes, nausea and vomiting, indigestion and acid reflux, burping and more serious problems like gallbladder problems, gallstones, pancreatitis, and intestinal obstruction

• Reduced kidney function

• A fast heart rate or abnormal rhythm

• Headache, dizziness, and/or tiredness

• Hair loss

• Sweating

• Skin reactions and rashes

If you're taking a GLP-1 receptor agonist, or considering starting one, a doctor or healthcare professional can discuss the relevant side effects and whether the medication is the best option for your needs.

Diabetes medication should be discussed with your GP or diabetes specialist, but the Quick Meds team are always available to discuss your weight loss goals and answer any questions about GLP-1 receptor agonists.

Deciding If GLP-1 Agonists Are Right for You

The doctor managing your diabetes medication will be able to discuss whether they think it's a good idea to add a GLP-1 receptor agonist to your treatment regime. Usually this is for people who have tried taking three other diabetes medicines or people who are unable to take other medications.

For weight loss, GLP-1 receptor agonists are only prescribed on the NHS by doctors with special training or through a weight loss clinic. If you want to start taking a weight loss injection like Wegovy or Mounjaro, you can also get a prescription from a private weight loss service like Quick Meds.

You'll still have to meet specific criteria in order to receive the drug. This means you must have first tried to lose weight by making changes to your diet and exercise regimen, and that you must have a body mass index (BMI) of either:

• 30 kg/m2

OR

• 27 kg/m2 with a weight-related health condition

If you meet these criteria, you'll need to discuss treatment with a healthcare professional before getting started to make sure you don't have any other health problems that make the medication unsuitable for you.

This is also an opportunity to make sure you understand the possible risks and side effects and to discuss your weight loss goals. For more information, start a free online consultation with the Quick Meds team today.

Conclusion and Summary

GLP-1 agonists are helpful tools in the treatment of type 2 diabetes and obesity, but their health benefits extend to more than just weight management and diabetes. As well as reducing the risk of cardiovascular disease and kidney injury, these medications can also lower inflammation levels in many areas of the body.

Research is ongoing into the future uses for these medications to treat inflammatory diseases and support other areas of health.

Before starting GLP-1 agonist treatment, it's important to seek advice from a medical professional to make sure it's safe for you. Here at Quick Meds, our team of highly trained healthcare professionals is always available for advice. If you're considering starting a GLP-1 agonist to help with your weight loss journey, book a free online consultation with the team today.