Overview

Glucagon-like peptide 1 agonists, also known as GLP-1s, are a class of medications used to treat type 2 diabetes and obesity. GLP-1s have rapidly gained attention recently for their impressive ability to lower blood sugar in those with type 2 diabetes and, more significantly, drastically induce weight loss in those with obesity.¹ Drugs like Ozempic, Wegovy, and Mounjaro have now become household names for weight-loss solutions. But whilst showing promising results for fat loss, the question of what these medications do to our muscle mass also comes up. Some studies show that taking these medications can lead to potential side effects such as reductions in lean body mass and skeletal muscle quantity, health, and function.

Preserving muscle in our body is extremely important since muscle plays a vital role in controlling all movement in our bodies, as well as strength, posture, balance, metabolism, energy storage and long-term physical health and function.² In this article, we will explore how GLP-1s work, what the current research shows about their impact on muscle mass, and how to protect muscle while using them.

What are GLP-1 receptor agonists?

Glucagon-like peptide-1 (GLP-1) is a hormone that naturally occurs in the body, made in the small intestine. It has several important roles such as:

• Triggering insulin secretion from the pancreas – insulin is an important hormone that allows us to get energy from the food we eat. It lowers the amount of sugar (glucose) in our blood. If we don’t have enough insulin, this leads to our blood sugar levels increasing and to diabetes¹
• Blocking the secretion of glucagon – glucagon is a hormone that is needed to raise our blood sugar levels when they get too low, so GLP-1 stops more glucose from going into your bloodstream¹
• Slowing the emptying of the stomach – slower digestion means less glucose is released from the food we eat into the bloodstream¹
• Increasing how full you feel after eating (satiation) – GLP-1 affects areas of the brain, such as the hypothalamus, which process and regulate the feelings of hunger and satiety, which helps with suppressing our appetite³

GLP-1 receptor agonists are a class of medications that mimic the effects of this hormone. An agonist is a drug or manufactured substance that binds to receptors on our cells and causes the same action to happen to the receptor as the substance that normally binds to it.⁴ This means GLP-1 agonist medications bind to GLP receptors and trigger the roles of the GLP-1 hormone and enhance the effects of naturally occurring GLP-1. If you have type 2 diabetes, this means you can manage your blood sugar as more insulin can be triggered to release from the pancreas, as well as slowing your digestion to decrease blood sugar spikes. If you are obese, the combined effects of slow digestion, satiation and hunger suppression reduce food intake, resulting in weight loss.¹

Currently, the Food and Drug Administration (FDA) has approved the use of the GLP-1 agonists semaglutide and liraglutide for both managing type 2 diabetes and obesity. Semaglutide (most commonly known as Ozempic) treats both type 2 diabetes and obesity, and Wegovy, which treats obesity.¹

GLP-1 agonists are most often given as subcutaneous injections into areas of fatty tissue under the skin, such as the thighs, backs of your arms, stomach, and upper buttocks. The frequency of these injections can range from once a day for drugs such as liraglutide to once a week for drugs such as semaglutide, and can often be done by yourself at home.⁵

Understanding muscle mass and its importance

Muscle mass is the total amount of muscle in the body and is important for our overall health. It is often talked about along with lean body mass, which also includes muscle. But also, our bones, organs, skin and fluids.

There are three types of muscle in the body: skeletal, cardiac, and smooth. In this case, skeletal muscle is most significant, which makes up about 40% of the muscles in our body. Skeletal muscle is the muscle that is needed for movement as well as for supporting physical functions such as strength, posture, and balance. It also controls our blood sugar levels by regulating how much sugar we take in from the food we eat into our bloodstream. It also plays a big part in metabolic function, where we turn our food from calories into energy, storing nutrients, and maintaining body temperature.^6,7

Maintaining good muscle mass becomes more important as we get older and when facing long-term health issues such as diabetes, cancer or heart problems. Losing muscle mass is common as we age - called sarcopenia and is associated with being frail, more likely to fall, breaking bones and reduced mobility. You are also more likely to lose muscle mass whilst being ill or being inactive for a while, which makes the healing process longer.

How GLP-1s might affect muscle mass

GLP-1 agonists are very effective at helping with weight loss, but a potential side effect is also losing muscle, not just fat. When you lose weight, no matter if it is from diet, surgery or medication, you tend to lose both fat and muscle.

Results from clinical trials show reductions in muscle mass alongside fat, though this is mixed. Results range from 15% or less of muscle loss of total weight loss to 40%-60% in muscle mass loss as a proportion of total weight loss in patients who had been given semaglutide.⁸

GLP-1s do not seem to cause muscle loss directly but rather create conditions where muscle loss is more likely to occur, as well as can be due to several potential underlying factors, such as:⁸

• Older adults, with age, we naturally lose muscle (sarcopenia)
• Those with pre-existing muscle-wasting diseases or conditions, such as cancer
• Those using GLP-1s for rapid and significant weight loss
• Those who do not do much physical exercise or are very inactive, and so are not maintaining or growing their muscles
• Those who do not have enough protein in their diet due to suppressed appetite, which is needed to maintain and build muscle tissue

Ongoing and future clinical trials and research on GLP-1 drugs and more therapies for weight loss need to focus on muscle mass and body composition, along with how muscles function and move, to understand how GLP-1s affect the muscle health of many people who will use them for a long time ahead.⁸ There are also currently not enough long-term studies to look for long-term results and side effects, or studies looking at the use of these drugs alongside factors such as exercise and diet plans.

How to protect muscle mass while using GLP-1s

Your doctor will advise you to work alongside a dietitian and fitness expert to include other therapies alongside whilst using GLP-1s, such as lifestyle and diet modifications and exercise.

Firstly, getting enough protein intake is key. When trying to lose weight, it is advised to eat 1.1 to 1.6 grams of protein per kilogram of body weight every day. This helps maintain and build muscle and stops the body from using muscle for energy. It’s very important to eat foods high in protein such as lean meats, fish, eggs, dairy, beans and soy. Research has also shown that taking additional protein supplements⁹ as well as other supplements such as creatine – an organic compound that provides energy to your muscles and leucine – an amino acid used by muscle to give energy that can further help build skeletal muscle alongside exercise and resistance training, though they should be used carefully.

Exercise such as resistance training using machines and/or free weights and endurance training such as cycling and circuit training 2 to 3 days a week is found to be more effective to help stimulate your muscles to maintain them as well as build more. Research has found that the combination of exercise and an appropriate diet alongside taking GLP-1s encourages a more gradual and healthy weight loss, losing more fat mass whilst maintaining muscle mass or building back skeletal muscle. Typically, a loss of 0.5 - 1kg a week is generally advised.⁹

Summary

GLP-1 agonists like Ozempic and Wegovy are drugs that are used to manage type 2 diabetes and obesity by lowering blood sugar levels and inducing weight loss. However, along with fat loss, a loss in muscle mass may also occur, especially in those with a bad diet or are physically inactive or are susceptible to conditions like sarcopenia. Maintaining muscle is key for strength, balance, metabolism, and overall health. While GLP-1s don't cause muscle loss directly, their side effects can cause muscle to be lost alongside fat. Using them along with eating protein-rich foods, resistance training, and taking supplements like creatine can preserve muscle. We need more long-term research studies to understand the extent to which these drugs affect our muscles.