GLP-1s: Fat Loss Miracle? Or Monster?
The facts about the use of Semeglutide, Tirzepatide, and Retatrutide for fat loss
I've been wanting to write this article for a while, because this topic absolutely fascinates me.
As a health and fitness coach for the past 10+ years, my primary focus has been helping people get in better shape while leading healthier, more enjoyable lives in the process.
So anytime I come across a tool that could potentially help folks struggling with weight and health do just that, I become extremely interested - while also trying to maintain a healthy level of skepticism. After all, for decades, the fitness industry has been rife with miracle pills, shakes, diets, supplements, snake oil, and more - all of which almost always turn out too good to be true.
And to be honest, when it came to the GLP-1/Semeglutide craze that’s exploded over the past year or so, I was skeptical. Because on the surface, it seems like another too-good-to-be-true miracle weight loss cure.
But, like any good health professional (or any human being, for that matter), I was open to learning more and having my mind changed.
And believe it or not, as I've learned more about these medications, my mind has been changed - way more than I thought, actually.
But I'll save those thoughts for the end. First, I want to dive into the basics of what these GLP-1-based medications are, how they work, their potential side effects, and more.
Disclaimer: The following is not medical advice and should not be used as such. The information below is for research and educational purposes only. I am not a licensed medical professional or doctor, and you should always consult with one before starting any medication or treatment.
What Are GLP-1s?
GLP-1 (glucagon-like peptide-1) receptor agonists began as treatments for type 2 diabetes, inspired by the body’s natural incretin hormones.
Glucagon is a hormone produced by the pancreas that plays a critical role in regulating blood glucose levels. Its primary function is to raise blood sugar by stimulating insulin release when it falls too low, which it does by signaling the liver to break down stored glycogen into glucose and release it into the bloodstream. This process ensures the body has an adequate energy supply, especially during fasting or between meals.
The most well-known GLP-1, Semaglutide, was developed by Novo Nordisk and approved in 2017 for type -2 diabetes under the brand name Ozempic. However, it quickly gained attention for a surprising side effect: significant weight loss.
This unexpected benefit led to its rebranding as Wegovy for obesity management. From that point on, pharmaceutical companies have been looking for ways to enhance the weight loss effects of Semaglutide, leading to more advanced medications in Tirzepatide and Retatrutide.
GLP-1s for Dummies: How These Peptides Work
Semaglutide (Ozempic, Wegovy)
Semaglutide mimics GLP-1, a hormone that boosts insulin, suppresses glucagon, and slows gastric emptying. But its true power lies in how it communicates with the brain, reducing appetite significantly and, by extension, caloric intake.
Clinical trials, involving a diverse group of participants with type 2 diabetes, showed weight loss of up to 15% and significant improvements in blood sugar control over a 68-week period (source).
Tirzepatide (Mounjaro)
Tirzepatide takes things a step further by activating both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors.
GIP is an incretin hormone released after eating, which stimulates insulin secretion in a glucose-dependent manner. Activating GIP receptors enhances insulin response and may improve lipid metabolism, leading to better blood sugar control and potentially aiding in weight loss by improving satiety and energy storage regulation.
This dual action enhances insulin sensitivity while further curbing appetite. Participants in trials achieved up to 20% body weight reduction, outperforming semaglutide in head-to-head comparisons (source).
Retatrutide
Retatrutide is the latest and most advanced option, targeting GLP-1, GIP, and glucagon receptors in a triple-action approach. While GLP-1 and GIP provide similar benefits to tirzepatide, it's the activation of glucagon receptors that sets retatrutide apart.
Glucagon stimulates the liver to convert stored glycogen into glucose and also plays a significant role in increasing energy expenditure. When retatrutide activates glucagon receptors, it ramps up the body's metabolic rate and promotes fat oxidation—meaning your body starts burning more fat for energy rather than relying solely on stored carbohydrates. This leads to enhanced fat loss, even in the absence of extreme calorie restriction.
Additionally, GIP activation supports insulin sensitivity and improves IGF-1 (insulin-like growth factor) signaling, which contributes to muscle maintenance and even anabolic (muscle-building) effects. This makes retatrutide especially promising for preserving lean body mass while losing fat—a major limitation with many other weight loss approaches.
Early trials show unprecedented weight loss of up to 24% over 48 weeks, along with substantial improvements in blood sugar regulation, insulin levels, lipid markers, and cardiovascular health (source).
Comparison
The Health Benefits: More Than Just Weight Loss
Semaglutide
Supports up to 15% weight loss by significantly reducing appetite and calorie intake.
Improves glycemic control through enhanced insulin secretion and reduced glucagon levels.
Decreases gastric emptying, which prolongs satiety and helps control blood sugar spikes.
Associated with reduced blood pressure, lower cholesterol, and improved cardiovascular outcomes.
Tirzepatide
Provides greater weight loss potential (up to 20%) than semaglutide due to its dual agonist nature.
Activates both GLP-1 and GIP receptors to amplify insulin sensitivity and satiety.
GIP activation enhances lipid metabolism and supports better energy partitioning.
Demonstrates superior improvements in HbA1c, fasting glucose, and cholesterol levels.
Retatrutide
Leads the pack with up to 24% weight loss by combining GLP-1, GIP, and glucagon receptor activation.
Boosts fat oxidation and energy expenditure via glucagon receptor stimulation.
GIP-driven IGF-1 support promotes muscle retention and potential anabolic benefits.
Improves metabolic flexibility and dramatically enhances cardiovascular and metabolic markers including triglycerides, non-HDL cholesterol, insulin levels, and waist circumference.
What About Side Effects?
While the benefits are impressive, these peptides aren’t without drawbacks. Here are the most common side effects:
Semaglutide
Nausea, vomiting, and diarrhea (especially at the start).
Rare cases of pancreatitis and thyroid tumors.
Tirzepatide
Gastrointestinal discomfort: nausea, diarrhea, constipation.
Injection site reactions.
Rare risks of pancreatitis and thyroid issues.
Retatrutide
Nausea (45%), vomiting (19%), and constipation (16%).
Rare side effects like fatigue, temporary liver enzyme elevations, and pancreatitis.
Gastrointestinal symptoms are the leading cause of discontinuation.
Intestinal distress seems to be the most common side effect of these medications, with the severity increasing as the dosage increases. Some of this can be mitigated by spreading out the dose into multiple injections throughout the week.
Longer-term side effects aren’t as clear. There are concerns about pancreatitis and thyroid issues, and people already at risk for those issues are generally advised not to take GLP-1s.
Always consult with a medical professional of course.
The Downside of GLP-1s
One of the most common pieces of feedback I've heard from both healthcare professionals and individuals using GLP-1s is just how powerful the appetite suppression can be.
People don’t feel hungry. They feel fuller, faster. Cravings disappear.
In some cases, these medications even seem to help reduce addictive tendencies—toward food, alcohol, or other behaviors.
But here’s the issue: some users end up eating too little.
Now, if your goal is weight loss, that might sound like a good thing.
But it’s not.
The body is designed to conserve energy. And one of the most energy-intensive tissues to maintain is muscle. This is why someone with a higher percentage of muscle mass can eat more calories and maintain their weight than someone of the same weight but with higher body fat. Muscle is metabolically expensive.
In a prolonged calorie deficit, especially if you're not strength training or getting enough protein, the body won’t just burn fat—it will burn muscle too.
This leads to:
Slower metabolism
Decreased thyroid and testosterone levels
No meaningful change in body composition despite lower scale weight
Higher risk of injury and age-related physical decline
In other words, if you're not following a structured health and fitness routine while using GLP-1s, you might lose weight—but you won't necessarily end up that much healthier.
That’s why I strongly recommend using these medications under the guidance of both a qualified medical professional and a coach who understands exercise, nutrition, and the role each plays in metabolic health.
Should You Use GLP-1s?
If you’ve struggled with your weight for years…
If you’re significantly overweight or obese…
If you want to increase your energy, improve longevity, or just finally get results after trying everything else…
Then yes - GLP-1s might be a fantastic tool for you.
I’m not a doctor. I’m not here to prescribe. But from what I’ve seen, these peptides are the closest thing we’ve ever had to a true metabolic reset button.
That said - these only work long-term if you put in the work alongside it.
If you’re not willing to:
Eat a balanced, nutrient-dense diet
Strength train 2-3x per week
Prioritize sleep and manage stress
Then don’t waste your time. Because like almost everything else, these medications amplify healthy habits - they don’t replace them.
We’ve been chasing a miracle fat loss pill for decades. And GLP-1s may be as close as we’ve ever come. But they still have to be used intelligently. And they still require a healthy lifestyle to work to maximum effect.
But, if you’re willing to commit to that? These medications can potentially put fat loss into Easy Mode.
One Last Thing…
Now, there are folks out there who say going this route is “cheating” or “taking the easy way out.”
And if you’re one of them, this is for you…
I lost 100 pounds the "hard way." It took me four years. I know the struggle of living overweight for the majority of my life and how hard it is to change decades of unhealthy habits.
And I think if someone wants to lose weight, has spoken with their doctor, and decides to use a GLP-1 to help them get there faster, easier, and more sustainably?
They should absolutely freaking use them.
There’s this weird mindset that seems to exist where if you had to suffer to succeed, or do things a certain way, then everyone else should have to as well.
However, if we have new tools or technologies that make life better - and safer - for people, we should use them.
I’ve heard from numerous people on these medications say that they don’t openly share their use for fear of being judged.
Which is really sad. But I understand. Because, unfortunately, you see a lot of unqualified keyboard warriors judging others for the use of GLP-1s all over the internet.
And to those folks I say…
F*ck all the way off. Seriously.
You have no right to judge or put down someone for the choices they make about their body - especially when it comes to trying to get healthier.
Yes, there may be long-term side effects we don’t fully understand yet. And yes, many doctors are probably overprescribing. Those are valid concerns for sure.
But at the end of the day, the choice to use any medication (and the risks associated) is up to the individual and their chosen healthcare professional(s).
As long as they’re making the most informed choice possible, that’s all I care about. Which is all you should care about too.
And here’s the last thing I’ll say…
We may not know all the long-term consequences of these treatments….
But we DO know the long-term consequences of obesity. They’ve been making our population sicker and killing people earlier for decades now.
So why wouldn’t we responsibly use every tool we have to fight against that?
Especially when the results can be life-changing.
Thanks for reading,
Coach Jorden
Thoughts or experience with GLP-1s? I’d love to hear them in the comments!