“How Big Pharma Hijacked Your Appetite—And Called It Healthcare.”
It started with a shot.
A weekly injection that promised to silence cravings, melt belly fat, and make you forget that you ever stopped at Taco Bell for late-night nachos.
But behind the rapid weight loss, celebrity endorsements, and TikTok transformations, something strange was happening.
People were losing muscle. Some claimed that their stomachs were literally shutting down. And they didn’t seem all that interested in… well, anything anymore.
This is The Peptide Files. And today, we’re diving back into the world of GLP-1 receptor agonists—a topic that remains as hot in headline news as it did when they hit the market years ago. These are peptides – but manufactured just differently enough that they could be patented as drugs – drugs that turned your metabolism into a subscription service, making billions of dollars for the pharmaceutical industry.
Let’s get into it.
I’ve talked about this before, but let’s go over it again: What Is a GLP-1?
OK – let’s break it down.
GLP-1 stands for Glucagon-Like Peptide-1—a hormone your gut naturally releases after you eat. It’s part of a brilliantly designed system engineered to:
- Slow down how fast your stomach empties
- Tell your pancreas to secrete insulin
- Lower blood sugar
- Make you feel full faster
- Ultimately improve insulin sensitivity
In other words, it’s one of the many hormones that help regulate metabolism in a balanced, intelligent, God-given way.
But behind the veil of mimicking nature, Pharma saw an opportunity—because when people started injecting synthetic versions of this hormone, their appetites plummeted. And so did their weight.
And thus began the Ozempic era.
The Mean Girls of Metabolic Medicine
Ozempic (also known as Wegovy or semaglutide) was basically first on the scene, and suddenly everyone from Hollywood elites to your cousin Becky was losing 30 pounds in three months. No gym. No kale smoothies. Just a once weekly injection.
But pharma wasn’t about to stop there. If hijacking one satiety hormone could rake in billions, might there be others?
Let’s meet the current cast of GLP-1 characters and their hormone sidekicks:
- Semaglutide (Ozempic/Wegovy) The OG GLP-1 receptor agonist. Semaglutide is just the one peptide – GLP-1. It wasn’t the first in this class, but it was and still is the strongest. It slows digestion, improves insulin signaling, and suppresses appetite. Average weight loss was 15% in clinical trials and the side effects are all the ones the press is screaming about – nausea, vomiting, gastroparesis (that’s slowing down of the stomach emptying), emotional ‘numbing’ and yes, muscle loss.
- The OG GLP-1 receptor agonist.
- Slows digestion, improves insulin signaling, suppresses appetite.
- Weight loss: ~15% in trials.
- Side effects: nausea, vomiting, gastroparesis, emotional numbing… and yes, muscle loss.
- Tirzepatide (Mounjaro/Zepbound) This is a dual agonist meaning it contains 2 different peptides made by your gut – GLP-1 plus GIP or glucose dependent insulinotropic polypeptide. This is like semaglutide’s bigger, bolder, more aggressive cousin. Average weight loss was a staggering 21% in clinical trials – eclipsing bariatric surgery for many patients. Same side effects, higher risk of lost lean muscle mass without proper support.
- A dual agonist: GLP-1 plus GIP (Glucose-Dependent Insulinotropic Polypeptide).
- Think of it as semaglutide’s bigger, bolder, more aggressive cousin.
- Weight loss: Up to 21% in studies—eclipsing bariatric surgery for some patients.
- Same side effects, plus a higher risk of lean mass loss without proper support.
- Retatrutide (still in clinical trials) Eli Lily still has this in clinical trials but I may have seen it available like a year ago already from ‘research pharmacies’. Retatrutide is no doubt the overachiever of the group combining GLP-1, GIP, and a third peptide – glucagon receptor agonist. Another peptide made by your gut. That third peptide throws a few more questions into the mix. We have a pretty good understanding of the activities GLP-1 and GIP have on the body in the short and long term, but not so much when it comes to constant glucagon activation. What impact might this have on other organs in the endocrine system like the adrenals and thyroid? What about long term metabolic flexibility? Lily’s still working out the kinks on this, but don’t think for a second that will keep this drug from officially coming to market. Early clinical trial data demonstrates up to 24.2% weight loss. Seriously. That’s like chopping off your entire left leg and half of your right.
- The ambitious overachiever of the group—combines GLP-1, GIP, and glucagon receptor agonism.
- Weight loss in early studies? Up to 24.2%—yes, really.
- Here’s the catch: it’s not FDA-approved yet, and we still don’t know what happens when people take this long term.
- Also unclear: what does constant glucagon activation do to the adrenals, thyroid, or overall metabolic flexibility?
It’s being positioned as the “ultimate fat burner,” but we’re still guessing about the long-term effects. Think: metabolic power tool… with the manual still being written.
- Cagrilintide (very early clinical trials) So this is exciting. Or horrifying. Cagrilintide (or Cag as it goes by in biohacking zones) is a synthetic amylin analog – that’s a peptide made by your pancreas meant to mimic another naturally occurring satiety hormone. Amylin enhances this slow gastric emptying situation. If you never want to eat or feel a survival emotion called ‘hunger’ ever again, cagrilintide is here for you. All by itself, ‘Cag’ isn’t all that remarkable, but pharma’s real play here is combining it with the GLP-1s. You thought Sharon Osbourne looked horrifying from Ozempic – imagine our outcomes with Cag on board. Like retatrutide, Cag isn’t officially on the market yet but like retatrutide, back channel peptide compounders are already compounding and selling it for research.
- A synthetic amylin analog, meant to mimic another naturally occurring satiety hormone.
- Amylin works alongside insulin to slow gastric emptying and increase feelings of fullness.
- Alone, it’s a bit underwhelming—but pharma’s real play here is combining cagrilintide + semaglutide for an even more powerful appetite suppression effect.
- Trials are underway, but we’re still in the infancy phase—meaning no FDA approval yet, and very limited data.
The pros? Enhanced appetite suppression and potentially greater weight loss.
The cons? Unknown safety, synergistic side effects, and an even higher risk of creating metabolic dependency.
So, to recap:
We’ve gone from targeting one hunger hormone… to two, three, maybe four, all layered together to take overweight Americans from looking like this, to this. Don’t get me wrong, I’m a fan of the GLPs in the right hands with the right supervision, but that’s not what’s happening here. If your regular doctor is smart enough to realize he or she doesn’t know the first thing about these medications and refuses to write a script, you can just get online – sign up for a subscription service. These drugs can be shipped right to your front door without ever seeing a doctor. Standing on a scale. Having your labs checked, your body composition monitored. Ever.
The Stack Hack
Now here’s something you didn’t hear from me…
But it’s making the rounds in the biohacking world, so we’re going to talk about it—because not talking about it doesn’t make it go away.
There’s a growing number of people online who are:
- Combining multiple GLP-1 receptor agonists, sometimes in lower doses
- Adding small doses of cagrilintide to their semaglutide, tirzepatide, or retatrutide regimens
- And even tinkering with other non-FDA approved peptides in DIY-style weight loss stacks
The theory?
Stacking at subtherapeutic doses might provide similar weight loss benefits with fewer side effects. Kind of like a “microdosed metabolic stack.”
The reality?
Well, we don’t really know. There are no safety studies, no long-term data, and no regulation. Just people experimenting on themselves with peptides purchased from gray market suppliers who may or may not be making them in their basement next to their bath salts. Just saying.
And listen, I get it. People are desperate for solutions. And some of those folks have a good handle on physiology and how these things work. But when you start mixing powerful hormones that affect insulin, satiety, dopamine, and digestion at the direction of the same guy at the gym selling bootlegged steroids – I….I would seek more reputable counsel.
So while I am telling you this exists, I’m also telling you—don’t try this on your own.
Side Effects May Include… Everything You Didn’t Sign Up For
Do these peptides work for weight loss and potentially improve long-term insulin sensitivity. Yes – but the mainstream narrative tends to leave out some important side effects we should be mindful of.
- Muscle loss – Up to 40% of the weight lost isn’t fat. It’s lean tissue. Not exactly what you want when you’re trying to boost metabolism.
- Gastroparesis – In some people, the stomach literally stops functioning. And no, it doesn’t always recover.
- Emotional blunting – Appetite is gone, but so is joy. People describe feeling flat, numb, disinterested—even depressed. This is a relatively newly recognized side effect. I’ve had patients report feeling absolutely great on GLPs. Energy is better. The food noise is gone. But for some people, they apparently just stop feeling anything at all.
- Rebound weight gain – If you stop taking the drug? The weight almost always comes back. Sometimes with a vengeance. Why is this? Well, if you go back to eating the same crap you were eating before are we supposed to be shocked by this?
These medications used to be tools for people with type 2 diabetes, but times have changed. The majority of users now are non-obese, non-diabetics looking for cosmetic weight loss. Oh, and kids. Did I mention the kids? Semaglutide is FDA approved for use in children as young as 12 for weight loss. What happens to a person started on a once weekly shot to control weight and metabolic dysfunction at the age of 12, ten years from now? 20? Meh – guess we’ll find out.
This Stuff Rewires Your Brain
This isn’t just about your gut.
GLP-1 agonists cross the blood-brain barrier and affect dopamine, reward, and behavior. That means:
- Reduced food cravings.
- Decreased interest in alcohol, cigarettes, even compulsive behaviors – I think we can all agree that these are good things.
- But now that these peptides have been on the market for this long and so many people are using them, we’re seeing some reports of not so great brain activity… diminished joy, apathy, and personality changes.
When hunger disappears, what else goes with it?
Follow the Money
If you’re wondering why you’re seeing commercials for Ozempic every 8 seconds… here’s why:
- Semaglutide alone is expected to rake in $18 billion this year
- Tirzepatide will likely become the highest-grossing drug of all time
- GLP-1s are the new Lipitor—and obesity is the new cholesterol
This is great news for pharma shareholders. Maybe not so great news for patients who are being told this is a long-term solution instead of a short term tool to shed some unwanted pounds and improve insulin resistance.
These drugs alone don’t fix the problem.
If significant diet and lifestyle changes aren’t implemented at the same time, these peptides basically rent control over your metabolism. The minute you stop paying? The benefits vanish. And just when you thought pharma’s mad scientists couldn’t get any crazier… enter orforglipron.
But Wait, There's More... Meet Orforglipron
Here comes the next act.
Orforglipron. Catchy, right? It’s Eli Lilly’s brand new oral GLP-1 receptor agonist — but this time, it’s not even a peptide. They’re done with the ‘it’s something your body makes anyway’ angle. This drug (don’t make me say it again) is a small molecule drug designed to mimic the effects of GLP-1.
Why does this matter?
Well now, they can put GLP-1 agonists into a pill. For all you needle phobes out there, that means no more injections. No more pens. No cold chain shipping headaches.
Just a once-daily pop-and-go tablet for your permanent appetite suppression subscription.
It’s not FDA approved yet—but trust me, it’s coming. Fast.
Oh, and better yet – they’re also already working on combo drugs — blending orforglipron with other appetite-regulating hormones like amylin analogs (think: cagrilintide) to create multi-pathway oral weight loss cocktails.
Welcome to the future, friends.
Real Solutions
The truth is you don’t have to play hormone roulette to lose weight or reverse insulin resistance. These peptides certainly help but don’t believe the media spin that you can’t do it without them.
Here’s what naturally supports your GLP-1 pathway—without the expensive prescription:
- Berberine – Natural GLP-1 booster and insulin sensitizer
- Time-restricted eating/Intermittent fasting – Enhances GLP-1 and improves leptin sensitivity
- Protein-rich meals – Stimulate endogenous GLP-1
- Strength training – Preserves lean mass, improves insulin signaling
- Sleep, stress reduction, microbiome care – Yes, still matters
Weight loss isn’t just about less hunger.
It’s about better signaling, stronger mitochondria, and a metabolism that actually works.
Final Thoughts: Miracle Molecule or Metabolic Misdirection?
GLP-1 drugs are powerful. For some people, they’re genuinely helpful and, in the right hands, can not only improve numbers on the scale but reduce risk associated with all things related to insulin resistance and metabolic syndrome.
But there’s no easy button. Diet and lifestyle changes need to happen for there to be any long-term benefit. Body composition and labs need to be monitored to make sure you don’t get Ozempic butt. Or osteoporosis. Or go bald.
When Big Pharma suddenly becomes this interested in anything, you should pause and ask yourself:
Who benefits?
Who profits? Their plan isn’t for you to use these peptides like we do – as a tool to get back on track. I can guarantee their business model is to start these drugs as early as possible for as many indications as possible and market them for lifelong management. There’s no money in wellness people. Big medicine is big business…
