Understanding GLP-1s for Weight Loss

What Are GLP-1s?

Glucagon-like Peptide-1 (GLP-1) is a class of medications known as incretin mimetics. Incretin mimetics mimic the action of natural hormones like GLP-1 and glucose-dependent insulinotropic polypeptide (GIP).

Your body naturally produces GLP-1 and GIP. After eating, your gut signals to increase GLP-1 and GIP production. This cascading effect then alerts the pancreas to stimulate insulin production and help your body regulate blood sugar levels.

Blood sugar regulation is crucial for overall health and well-being. Maintaining stable blood glucose levels prevents diabetes and complications like heart disease, nerve damage, and vision loss. Regulated blood sugar supports better energy levels, mood, sleep, and cognitive function.

Initially, GLP-1 medications were primarily used in the medical setting to support patients with Type 2 Diabetes. Now, they are used in varying levels to support those who are overweight and obese. Between 2009 and 2015, 2% of adults eligible for weight loss medications took them— compared to 12% in 2024.

The rapid increase in use of GLP-1s for weight loss can be attributed to the rising rates of overweight and obesity and the availability of GLP-1s.

Natural vs. Manufactured GLP-1s

The difference between the body’s natural GLP-1 and GIP production is the concentration. At higher concentrations, GLP-1s impact the body in other ways. For example, the amount of GLP-1 found in your blood stream after administration of the medication is approximately 1,000 times higher than your body’s natural ability to create it after consuming food.

The higher doses (known as supraphysiological doses) of GLP-1 and GIP work in conjunction with several parts of your brain, including the hypothalamus, brainstem (specifically the nucleus tractus solitarius), and the mesolimbic system. This reaction reduces your hunger and increases the sensation of fullness and satiety after eating.

Call Out: Doses for Different Indications

Higher concentrations of GLP-1 and GIP are required for appetite suppressing effects while lower doses are sufficient for improving blood glucose control. The FDA-approved dosing of GLP1-s for weight loss is higher than the dosing approved for Type 2 Diabetes. For example, Semaglutide dosing is 0.5 mg to 2.0 mg weekly for Type 2 Diabetes and 2.4 mg for obesity.

The appetite suppression and fullness feeling enhance the effects of the GLP-1s and are successful for weight loss. During randomized controlled trials of GLP-1s, every trial resulted in weight loss driven by a meaningful reduction in calorie intake. The average reduction in calorie intake across the trial was between 300 and 800 calories (about 64 minutes of running) per day.

GLP-1 Medication Differences

The GLP-1 market is rapidly changing with various medications from many brands. Most notably, brand names like Ozempic, Rybelsus, and Wegovy are synonymous with GLP-1s.

Regardless, each brand differs in their dosage and intended use. For instance, some brands target GLP-1 in isolation or both GLP-1 and GIP.

Additionally, in more recent years as a response to medication shortages, compounded GLP-1s have risen in popularity. However, compounded GLP-1s are not Food and Drug Administration (FDA)-approved and vary in strength, delivery method, and ingredients. Generally, the quality of compounded medications, including GLP-1s, can differ across pharmacies, depending on their practices and the ingredients they use.

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The FDA has issued warnings about compounded GLP-1s, citing safety concerns, including dosing errors, inconsistent ingredients, and potential contamination.

The History of GLP-1s for Weight Loss

Some GLP-1 medications, like exenatide (Byetta) and indirectly, semaglutide (Ozempic, Wegovy), were inspired by a protein found in the venom of the Gila monster, a venomous lizard native to the southwestern United States.

Dr. John Eng, endocrinologist, studied the venom of the Gila monster and discovered exendin-4, a peptide like human GLP-1 in 1990. This discovery led to the development of exenatide, a synthetic form of exendin-4, which was the first GLP-1 receptor agonist approved for treating Type 2 Diabetes.

Call out: Brand Potency

Semaglutide, marketed as Ozempic and Wegovy, is a more potent and longer-acting GLP-1 receptor agonist. Though not directly derived from Gila monster venom, the initial success of exenatide paved the way for the development of other GLP-1 drugs, including semaglutide.

Since then, studies have evolved to include GLP-1s for weight loss—the first published in 2015. The 2015 clinical trial focused on GLP-1 as a weight loss aid. This study included daily injections of 3.0 mg of Liraglutide in those who were overweight or obese in conjunction with lifestyle modification. Participants lost approximately 19 pounds.

Due to increased availability and widespread use, it is important for fitness and wellness professionals to fully understand GLP-1s, their use, and how you can support clients in their weight loss journey.

GLP-1s Side Effects

Like all medication, side effects exist. There are growing concerns regarding GLP-1 use, as noted in randomized trials. The rate of adverse side effects among those using GLP-1s for weight loss is 70-90%, whereas serious adverse side effects are less than 10% and fatal events less than 0.1%.

The most common adverse GLP-1s side effects are related to gastrointestinal issues, specifically nausea, vomiting, diarrhea, constipation, and indigestion. These symptoms occur in 10-40% of people and vary in type and severity.

In addition to adverse side effects, some experience contraindications (a specific reason someone should not use the medication).

Call out: Contraindications

Contraindication is a specific situation where a medication, procedure, or exercise should be avoided because it may prove to be harmful to the individual.

GLP-1s have a few clear contraindications.

• Hereditary conditions, known as Multiple Endocrine Neoplasia type 2 (MEN2) or a history of Medullary Thyroid Cancer (MTC)
• History of pancreatitis
• History of severe gastrointestinal disorders
• Pregnancy or breastfeeding

While not specifically indicated by the FDA as a contraindication, it is not recommended that individuals with a normal body mass index (BMI) should use GLP-1s for weight loss.

Managing GLP-1s Side Effects

Most GLP-1s side effects happen because of slow gut motility (how quickly food moves through the gastrointestinal tract). Symptoms may be lessened or avoided by lifestyle changes, specifically eating patterns.

When coaching clients using GLP-1s for weight loss, recommending modifications to their eating and lifestyle habits is vital.

• Avoid overly aggressive deficits, except under medical supervision
• Avoid large-volume meals before bedtime
• Consider supplementing digestive enzymes if appropriate, and physician approved
• Eat 3-4 smaller meals and a few snacks a day instead of larger meals
• Ensure adequate hydration
• Focus on nutrient dense foods and supplementation as needed. Common micronutrient deficiencies while taking GLP-1s include vitamin D, calcium, vitamin B12, and iron
• Increase protein intake
• Limit alcohol and carbonated beverages
• Reduce the frequency of higher fat meals

Although GLP-1s do show substantial and meaningful weight loss, studies show 30-60% of weight loss includes lean muscle mass, leading to decreased bone density. Certified personal trainers working with clients using GLP-1s for weight loss must also consider movement modifications to counteract the medication’s impact.

• Cardiovascular training: Avoid excessive cardio volume that could impair recovery. Use walking, cycling, or internals and include approximately three hours of moderate-intensity aerobic exercise.
• Low volume: Clients may experience fatigue or nausea when taking GLP-1s for weight loss, which can hinder performance. Start with lower volume activity and gradually increase as tolerated.
• Resistance training: Aim for 2-4 strength sessions per week using various modalities, focusing on compound movements—use moderate to heavy loads and progressive overload to stimulate muscle retention.

Weight loss medications are a valuable tool for weight loss and reducing the risk of chronic diseases associated with obesity. As a certified personal trainer, you’re likely to encounter a client taking GLP-1s for weight loss: roughly one in eight adults in the United States report using GLP-1s within the last year.

This rising popularity makes it even more important for fitness and wellness professionals to stay up to date with evidence-based recommendations. Gain the knowledge to safely and effectively guide clients taking GLP-1s toward improved health and well-being. Our course Understanding Weight Loss Medications digs into scientific research, covers practical applications, and shares insights from industry experts so you maximize sessions and effectively support clients using GLP-1s for weight loss.

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