The Hidden Costs of GLP-1 Drugs for Weight Loss

By Cyrus Khambatta, PhD

Over the past two years, GLP-1 receptor agonist drugs (GLP1-RAs) including Ozempic, Wegovy, Mounjaro, and Zepbound have become extremely popular for weight loss. Everywhere you turn, millions of people who have been trying to lose weight unsuccessfully are now being prescribed these drugs for long-term use.

Doctors love prescribing GLP-1 RAs for many reasons, but one of the most important is dangerously simple:

GLP-1 receptor agonist drugs are the most powerful appetite suppressing drugs ever created by the pharmaceutical industry.

Originally developed to reduce blood glucose in type 2 diabetes, this class of medications has gained widespread popularity for people wanting to lose anywhere from 10-200+ pounds.

If you’re considering using Ozempic, Wegovy, or Mounjaro for weight loss, take a moment to read this article about the pros and cons of long-term use.

I’ve compiled this comprehensive guide to help you make an informed decision about these increasingly popular medications, so that you’re armed with the science that your doctor may not know.

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

GLP-1 receptor agonists (GLP-1RAs) are synthetic medications designed to mimic the actions of glucagon-like peptide-1 (GLP-1), an incretin hormone primarily produced by L-cells in your small intestine in response to nutrient ingestion, including glucose, amino acids, and fatty acids.

These drugs mimic the effects of endogenous (self-made) GLP-1, but are engineered to be resistant to degradation so that they can remain active in your blood for up to 7 days.

They were originally developed to manage type 2 diabetes but have gained enormous popularity for their weight loss effects. The most common ones include:

• Semaglutide (sold as Ozempic for diabetes and Wegovy for weight loss)

• Tirzepatide (sold as Mounjaro for diabetes and Zepbound for weight loss)

• Liraglutide (sold as Victoza for diabetes and Saxenda for weight loss)

How Do They Work in Your Digestive System?

GLP-1RAs do some important work in your digestive system, including your stomach, intestines, and pancreas.

• Increasing Insulin: When you eat food, your blood glucose rises. These drugs tell your pancreas to release insulin when your blood glucose is elevated, but not when your blood glucose is normal. In this way, they’re incredibly safe because they don’t cause low blood glucose (hypoglycemia).

• Lowering Glucagon: Glucagon is another hormone secreted by the pancreas that tells your liver to release stored glucose into the blood. GLP-1 RAs inhibit glucagon from being released into circulation when your blood glucose is high, which prevents your blood glucose from going even higher.

• Slowing Down Your Stomach: These drugs slow down the rate at which food leaves your stomach (otherwise known as gastric emptying). This means that glucose from food enters your blood slowly, which prevents blood glucose “spikes” after meals. In addition, slowing your gastric emptying rate also makes you feel full for an extended period of time.

How Do They Work in Your Brain?

GLP-1 RAs are also engineered to cross the blood brain barrier (BBB) and communicate directly with your hypothalamus, a region of your brain responsible for controlling your appetite, your thoughts about food, and your general feeling of satiety.

• Reducing Hunger in Your Hypothalamus: In your hypothalamus, GLP-1 RAs tell your brain that you’re not hungry. In response, your hypothalamus reduces your desire to eat food, making you feel full, even if there’s no food material in your digestive system.

  This reduces your desire to eat food, and also makes you feel satisfied with smaller meals. Think of it as your hypothalamus saying, “I’m full, now it’s time to stop eating!”

• Reduce Cravings and Addictive Behavior: GLP-1 RAs can also influence regions of your brain that control food cravings, so your desire to snack and/or eat unhealthy foods also diminishes. Therapists are now recognizing the powerful effects that GLP-1 RAs have on reducing addictive tendencies, and ongoing research will likely provide more information as new information emerges.

In the image below, you can see that the GLP-1 secreted in the small intestine then tickles the vagus nerve, which in turn sends an electrical signal to the hypothalamus to reduce appetite:

Baggio LL, Drucker DJ. Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight. J Clin Invest. 2014 Oct 1;124(10):4223–6.

What Clinical Trials Show

The effectiveness of GLP-1 RAs for weight loss has been demonstrated in several landmark clinical trials:

STEP-1 Trial (2021)

In this pivotal study published in the New England Journal of Medicine, researchers from Northwestern University investigated once-weekly 2.4mg semaglutide injections in 1,961 non-diabetic patients with either a BMI of 30+ or a BMI of 27+ with weight-related health issues.

The results were impressive:

• Semaglutide group: 14.9% average weight loss after 68 weeks

• Placebo group: only 2.4% weight loss

• 86.4% of semaglutide patients lost at least 5% of their body weight

STEP-2 Trial

Published in The Lancet, this trial compared different doses of semaglutide (1.0mg vs. 2.4mg) against placebo in 1,210 participants over 68 weeks:

• 2.4mg weekly: 9.64% weight loss

• 1.0mg weekly: 6.99% weight loss

• Placebo: 3.42% weight loss

The higher dose also achieved better glycemic control and reduced cardiometabolic risk factors.

STEP-3 Trial

This study examined semaglutide combined with intensive behavioral therapy in 611 participants:

• Semaglutide + behavioral therapy: 16.0% average weight reduction

• Placebo + behavioral therapy: 5.7% weight reduction

STEP-4 Trial

This trial revealed what happens when patients stop taking the medication. After 20 weeks on semaglutide, 902 participants were either continued on the drug or switched to placebo:

• Continued semaglutide: additional 7.9% weight loss (total 17.4%)

• Switched to placebo: 6.9% weight regain (ending with only 5.0% total loss)

STEP-5 Trial

This long-term study evaluated semaglutide 2.4 mg versus placebo in maintaining weight loss over a 2-year period in 304 participants, and reported:

• Significant weight loss until week 60

• Effects maintained through week 104

• Average placebo-corrected weight loss of 12.6% at the end of 2 years

These studies provide strong evidence that GLP-1 RAs can be effective for both weight loss and type 2 diabetes management, and the combined benefits have led to a surge in prescriptions, reaching approximately 40 million in the U.S. in 2022.

However, they also reveal a critical limitation: when patients stop taking the medication, substantial weight regain occurs.

What are the Side Effects of GLP-1 RAs?

While the weight loss benefits are impressive, GLP-1 RAs come with significant side effects and risks that aren't always prominently discussed with patients at the time of prescription.

Common Gastrointestinal Side Effects

Researchers from British Columbia analyzed a random sample of 16 million patients from the PharMetrics Plus for Academics database (IQVIA), a large health claims database that captures 93% of all outpatient prescriptions and physician diagnoses in the US between the years 2006-2020. They included patients with a recent history of obesity, and excluded those with diabetes or who had been prescribed another antidiabetic drug.

They found that the administration of GLP-1 agonists is associated with a:

• 9.09 times higher risk of pancreatitis, inflammation of the pancreas

• 4.22 times higher risk of bowel obstruction, a condition characterized by the obstruction of food passage through the small or large intestine, leading to abdominal cramping, bloating, nausea, and vomiting

• 3.67 times higher risk of gastroparesis or stomach paralysis, a condition that restricts the passage of food from the stomach to the small intestine, resulting in symptoms such as vomiting, nausea, and abdominal pain

Patients using GLP-1 RAs also report experiencing other milder gastrointestinal side effects including:

• Nausea (affecting 17-22% of patients)

• Diarrhea (13-16%)

• Constipation

• Vomiting (6-10%)

• Excessive fullness

• Bloating and belching

• Heartburn

Muscle Loss Concerns

When people lose weight, typically 25-30% of weight loss comes from lean muscle mass. However, in the STEP-1 study, patients on semaglutide lost nearly 14kg total, with a concerning 5kg (38%) coming from lean mass, exceeding normal physiological expectations.

While weight loss improves life expectancy and increases metabolic health, rapid weight loss can have negative consequences, including:

• Rapid muscle loss

• Reduced bone density

• Decreased resting metabolic rate (RMR) (aka slower metabolism)

This accelerated muscle loss could increase the risk of sarcopenia (progressive loss of muscle mass and function), especially in older adults.

An analysis of 18 randomized control trials comparing the effects of many types of diabetes medications including GLP-1 RAs demonstrated that GLP-1 drugs promoted muscle loss more than in control subjects.

What this means is simple: while GLP-1 drugs may be enticing because they can help you lose weight fast, they also accelerate the speed at which you lose muscle mass, which can increase your risk for sarcopenia and osteoporosis.

The Rebound Effect: What Happens When You Stop

Perhaps the most troubling aspect of GLP-1 medications is what happens when patients stop using them. According to a comprehensive review published in 2024, weight regain after stopping GLP-1 RAs is significant and rapid.

A systematic review and meta-regression analysis published in 2025 found that after stopping GLP-1 medications, patients regain most of the weight. They discovered the following:

• Weight regain plateaus at approximately 75.6% of the weight lost during treatment

• At 1 year after stopping, only about 40.2% of the weight loss benefit remains

In the graph below, you can see that over the course of 60 weeks (just over 1 year), patients included in any of 6 human clinical trials ended up regaining between ~45-70% of the weight that they lost while using the GLP-1 drug:

This means that for most patients, GLP-1 medications represent a lifelong commitment rather than a temporary solution, unless they develop a strategic plan to keep the weight off when they stop taking the medication entirely.

As Dr. Nate Wood of Yale School of Medicine explained, "We generally do expect that when folks discontinue this medication they'll gain at least some weight back, if not all of it. And the reason for that is that we really think about obesity as a chronic disease. And chronic diseases require chronic treatment."

Long-Term Treatment is Becoming Increasingly Unaffordable

The cost of GLP-1 medications presents another significant barrier:

• Without insurance, these medications can cost between $1,000-$1,350 per month

• Insurance coverage is limited and inconsistent

• Medicare coverage is only available for diabetes treatment, not for weight loss

• Only 13 state Medicaid programs cover GLP-1s for obesity treatment as of August 2024

• Many insurers are actually dropping coverage due to high costs

Blue Cross Blue Shield of Michigan, for example, announced it will stop covering Wegovy, Zepbound, and Saxenda starting January 2025, affecting nearly 10,000 members. Other health systems like RWJBarnabas Health, Ascension, and Hennepin Healthcare have also ended or restricted coverage.

For most people, this means either paying thousands of dollars annually out-of-pocket or facing the prospect of weight regain when they can no longer afford the medication.

How to Lose Weight Sustainably Without GLP-1 Drugs

While GLP-1 RAs can be effective tools for losing weight, research consistently shows that lifestyle modification remains the most sustainable approach for long-term weight loss and health improvement.

A systematic review published in 2019 identified the most common habits among those who successfully maintained weight loss:

• Having healthy foods available at home

• Regular breakfast intake

• Increased vegetable consumption

• Decreased consumption of sugary and fatty foods

• Reducing fat in meals

• Increased physical activity (the strongest predictor of weight maintenance)

While these findings may not seem shocking, the reality is that most people:

• Often don’t practice these behaviors for extended periods of time

• Rarely combine multiple behaviors together

• Don’t get active and stay active, even though it’s the strongest predictor of maintaining weight loss

Another study found that among people who lost an average of 30kg and kept it off for 5.1 years, only 4.3% reported using medication as part of their weight loss strategy.

No matter how you slice it, maintaining long-term weight loss can often be more challenging than losing the weight initially, especially if the weight loss resulted mainly from the actions of a GLP-1 drug rather than modifying eating and exercise habits.

That’s exactly why we’re adamant about helping people who are using GLP-1 drugs develop lifestyle habits in real-time so that they can keep the weight off permanently.

Otherwise, the probability of maintaining weight loss over time without a fundamental change in your lifestyle is a challenging task that rarely works in the long-term.

We’ve Built an Approach That Keeps The Weight Off Permanently

We've helped thousands of people achieve permanent weight loss without relying on expensive medications with a laundry list of side effects. Our approach focuses on addressing the root causes of weight gain, high blood glucose, high cholesterol, and high blood pressure using natural methods that work like wildfire.

We’ve observed that many weight loss approaches fail in the long term because they focus only on food, and fail to help clients build an arsenal of tools that work for years to come. That’s why we’ve built a comprehensive program that works incredibly well over a 12-month period, because we provide our clients with the tools they need to guarantee success in the long-term.

We’ve developed a suite of proprietary tools over the past 20 years that have immense power when they’re incorporated together, including:

1. Developing a rock-solid mindset for long-term, sustainable habit change

2. Engineering your carbohydrate, fat, and protein intake to perfection

3. Optimizing your intake of fiber-rich foods at every meal

4. Incorporating polyphenol-rich foods with exceptional anti-inflammatory power

5. Incorporating nitrate-rich vegetables every day to improve oxygen delivery to tissues, stimulate mitochondrial growth, and lower blood pressure

6. Incorporating timed eating strategies to control calorie intake

7. Learning how to get to sleep and stay asleep, while maximizing the number of uninterrupted REM cycles every night

8. Resolving unresolved emotional trauma that gets in the way of losing weight permanently, and creating lasting habits that stick

9. Integrating cardiovascular exercise to increase energy expenditure, lower blood pressure, lower cholesterol, lower blood glucose, and promote dopamine synthesis

10. Integrating resistance training to build muscle mass, increase energy expenditure, improve insulin sensitivity, and decrease the risk of sarcopenia and osteoporosis

11. Learning how to eat before, during, and after exercise to accelerate muscle recovery and promote insulin sensitivity

These tools have taken us more than 20 years to develop, test, and perfect, and have proven to be extremely effective at helping people get to their ideal body weight and stay there for extended periods of time without the fear of “relapsing” to their original weight.

In fact, we actively discourage rapid weight loss because we understand the physiological backlash that occurs when rapid weight loss becomes unsustainable.

We help clients “engineer” their lifestyle to perfection, resulting in an approximate weight loss of 1.0-2.0 pounds per week, which results in 52-104 pounds of weight loss per year.

Our main focus is on developing an anti-inflammatory lifestyle which neutralizes whole body inflammation. By doing this, we’re able to address the root cause of weight gain, reduce the inflammation present in adipose and muscle tissue, and develop strategies that work in the long-term. Our clients experience:

• Gradual, sustainable weight loss without the rebound effect

• Improved insulin sensitivity

• Normalized blood glucose levels

• Reduced blood pressure and cholesterol

• Enhanced energy and vitality

• Freedom from food cravings and addiction

The Bottom Line: GLP-1 Drugs Have Hidden Costs

GLP-1 receptor agonists can be valuable tools for those with severe obesity or type 2 diabetes who haven't responded to other interventions. We recommend using them only for short periods of time, and only when you’re simultaneously working to change your thought patterns, eating habits, and movement patterns.

It’s imperative to understand that while GLP-1 drugs promote rapid weight loss, they come with significant drawbacks:

1. Side effects ranging from uncomfortable to potentially serious

2. Substantial weight regain when discontinued

3. High costs and inconsistent insurance coverage

4. Dependency on pharmaceutical intervention rather than addressing root causes

Before starting a GLP-1 medication, consider whether you're prepared for:

• Potential lifelong use of the medication

• Ongoing monthly costs

• Managing side effects

• The possibility of significant weight regain if you stop

For most people seeking sustainable weight loss and improved health, addressing the fundamental causes of weight gain through evidence-based lifestyle changes offers a more effective, affordable, and side-effect-free approach.

If you’re ready to get to your ideal body weight and stay there permanently, without the need for GLP-1 drugs, you’re in the right place. Click here to schedule a time to speak with us about our proven approach that has helped thousands of people lose weight permanently, decrease their dependence on pharmaceutical medication, increase their energy levels, and lower blood glucose, cholesterol, and blood pressure.

It may sound too good to be true, but trust me when I say that it isn’t. It takes hard work and a strategic approach, but our suite of research-backed tools is guaranteed to transform your life for the better, one step at a time.