Virtually everyone’s looking to lose some fat, build lean muscle or both.
Every once in a while, a breakthrough arises.
New “miracle” procedures, new diets, new supplement ingredients, new drugs.
Celebrities and influencers jump on board, and their testimonials take the world by storm.
Years or decades later, the scary truth comes out.
Serious health consequences.
Despite previously receiving full FDA approval.
Just another one of ~4,500 dangerous devices and drugs the FDA pulls from the market every year.
So in this post, we are going to explore the science of the latest class of weight loss “miracle” drugs — the GLP-1 agonists. I’ll share how they’re believed to work, the purported benefits, and the dangerous liraglutide, tirzepatide, and semaglutide side effects that will likely get these medications yanked off the market.
What Are the New Weight Loss Drugs (GLP-1 Agonists)
Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of drugs that mimic a natural hormone released when you eat food. These were originally synthesized to combat diabetes. Clinical trials showed a perplexing (and still not fully understood) side effect — massive weight loss due to appetite and craving suppression.
There are three primary GLP-1 drugs:
- Semaglutide (trade name Ozempic)
- Liraglutide (trade name Victoza)
- Tirzepatide (trade name Mounjaro)
Celebrities took notice, and testimonials from high-profile folks began rolling in. Spreading to Silicon Valley techies, models, athletes, biohackers, and anyone that can afford these expensive drugs. Even Elon Musk admits to using semaglutide.
The exact modes of action behind GLP-1 drugs are still unknown.
A few proposed mechanisms include:
- Reducing oxidative stress
- Stimulating insulin
- Inhibiting glucagon
- Slowing gastric motility (digestion)
- Uncoupling mitochondria
We’re still waiting on a lot more research to understand how these work. Based on the current science, theoretically, they shouldn’t have these effects.
But they do.
Benefits of GLP-1 medications
It’s not all bad. GLP-1 agonists appear to have some benefits.
There are other beneficial effects, too. Most of which are mice studies:
- Uncouples mitochondria
- Generates new mitochondria
- Lowers blood pressure
- Fewer food cravings
- Reduces inflammation
- Fewer cardiovascular issues
- Improved glucose tolerance
- Reduces visceral fat
Now, on to the main topic of this post. The less-discussed side effects and dangers of GLP-1 drugs.
Dangers of Semaglutide & Liraglutide
Although these are technically a class of safer molecules called peptides, interfering with complex systems always results in downstream problems.
GLP-1 agonist medications keep a transient signaling molecule sky-high. For a long time.
Violating key principles of bioharmony.
The research shows that over the long term (<2 years), they stop working and participants even begin putting weight back on.
Here’s the other major downside…
Weight loss does not equal fat loss.
We care most about the variables of body composition:
- Body fat
- Lean body mass (muscle)
It always consists of some ratio of both muscle and fat.
Fat loss is usually good and healthy. Weight loss is healthy, ONLY if the weight lost is mostly fat. Weight loss therapeutics therefore should reduce fat while keeping lean body mass the same or, ideally, increased. Increased fat loss rarely outweighs the huge risks associated with losing muscle.
I will most likely never use these drugs. As you’re about to learn, GLP-1 drugs burn muscle AND they even create new fat cells. When you stop using the drug, that fat may grow with a vengeance.
Listen to experts or read the commonly referenced articles, and the weight loss benefits of semaglutide are certainly impressive. Double-digit percentages in most trials. What’s there to dislike?
Well, these drugs still don’t have considerable long-term data behind them. One study investigating semaglutide found that weight loss plateaued around week 68.
From then to the end of the trial 104 weeks later, on average participants even regained some weight.
Semaglutide stopped working after week 68.
But here’s the real kicker.
Due to one particularly troublesome effect (mentioned next), to maintain the effects (if that’s even possible), you’ll need to use analogs of these drugs for the rest of your life. A paper assessing users after a year-long cycle found that virtually all of the benefits subsided after they quit using the drug. If that even works, increasing the dose would likely also increase the likelihood of experiencing side effects.
Creates new fat
We don’t fully understand how GLP-1 drugs work. One particular mechanism troubles scientists.
It seems that they generate new fat cells (increasing the creation and survival of new adipocytes). This mimics a process that naturally occurs only during youth as we need rapid growth.
These fat cells are not “inflated”/”full”, so you don’t gain extra weight while on the drug. But they increase in number. When the body has too much fat, it generates new “empty” fat cells to use for storage. These new fat cells don’t really go away.
It’s why long-term weight loss is difficult once you’ve gained the weight.
GLP-1 agonists increasing these fat storage “buckets” raises a major red flag.
Once you stop using them, there’s nothing to keep the bucket from filling.
Whenever you hear promised weight loss, pay attention.
Willpower aside, people could survive fasting for 2 weeks and lose a lot of weight. But it’d be metabolically active, highly beneficial, lean body tissue.
We don’t want that. Shedding lean tissue reduces healthspan and many key biomarkers of optimal health. At the same time, all weight loss efforts will result in some lean mass loss. Usually, 15-20% of total weight loss when done correctly.
Our goal is to maximize fat loss and minimize muscle loss. This is called improving body composition. Here lies the problem. The FDA doesn’t require clinical trials to use body composition as an endpoint for obesity research. An incredible and shocking oversight. So we don’t know how much of the loss is fat, and how much are muscle and bone.
In 2021, researchers performed a body composition scan (DEXA) on a small study of 140 patients. Lean mass made up about 39% of total weight loss. Nearly double that normal amount! A substudy showed that in 178 patients, on average 40% of the total weight loss was lean tissue.
If that doesn’t scare you away sufficiently, maybe the price will. GLP-1 drugs are super expensive.
Currently, monthly subscriptions cost about $1,500. Yes, $1500 per month. $18,000 per year for a medication with significant side effects.
That will probably come down significantly over time. Some health insurances cover it, but only for those diagnosed with obesity.
For biohackers and those looking for help dropping a few pounds, it’ll be inaccessible to all but those with the deepest pockets. Unless you go through a vendor of peptides that aren’t intended for human use.
The anti-aging community has somewhat of an obsession with fasting (AMPK, autophagy, mitophagy, etc) and a hatred of insulin. Though it’s powerful and has important roles, insulin’s often treated as public enemy number one.
That’s because chronically elevated insulin makes things grow. A potent anabolic for fat cells, muscle, cancer, etc.
So why is no one talking about the fact that…
GLP-1 agonists keep insulin chronically elevated.
While on the drug, users stay in a state of hyperinsulinemia.
Newer research is finding exactly that. Supraphysiologically sustained insulin, induced by GLP-1 drugs is associated with multiple cancer types.
Some medications are easy to dose and users rarely report side effects. Not the case here.
“…84.3% of participants reported adverse events, with gastrointestinal tract disorders reported by 71.4%”Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity
I’ve read plenty of horror stories of folks self-administering GLP-1 drugs, and doing the math wrong. In a few cases, 10Xing the recommended dose.
Unfortunately, with these two drugs, the primary side effects are quite unpleasant:
Perhaps the lack of cravings and appetite stems from the inability to hold food down.
Even among users that get the dose right, these side effects are the norm.
As more healthy biohackers begin using semaglutide, liraglutide, tirzepatide, and newer GLP-1 stimulating substances, I expect we’ll learn more about how these drugs impact crucial biomarkers of well-being.
Right now, studies only measure a narrow selection of health endpoints. This keeps trial costs lower at the cost of gauging the net positive/negative impacts.
Currently, the primary issue I’ve read about is the detrimental effect of semaglutide on resting heart rate. RHR during sleep is a key biomarker of nervous system status, circadian rhythm, and level of recovery. I track mine daily to plan my training routine and tweak my lifestyle accordingly.
Semaglutide use leads to long-lasting, sustained increases in resting heart rate.
Perhaps through chronically elevated insulin. Regardless of the cause, it’s another strike against these drugs.
I’m generally cautious with new drugs. Often new products hit the shelves, and somewhere between a few years and decades go by, and then a pivotal study brings all kinds of hazards to light. Resulting in regulatory agencies swooping in and banning the drug altogether.
Safe one day, public health crisis overnight.
But that’s not how it happens. These drugs were never safe.
And those are often drugs that “we understand well”.
Scientists still scratch their heads over this class of drugs. GLP1 receptor drugs should have literally the opposite effect. Weight gain.
If scientists unanimously hypothesize, based on everything else we know, that something should work one way—and it works the opposite—proceed cautiously.
From the research I’ve read, it seems these drugs won’t last.
Alternatives to Semaglutide, Liraglutide & New GLP-1 Drugs
Since we still don’t fully understand how they work, you probably wouldn’t want a pharmaceutical alternative to the popular GLP-1 drugs.
But there are also natural sources of GLP-1:
- Andean Tuber
- Yerba Mate
Both of these GLP-1 boosting foods/plants are bioharmonous.
They pulse the primary benefits (reduced cravings, reduced appetite, increased satiety) before returning to normal. Reducing the chance of grave consequences. More affordable and available too. Plus, these are proven safe over a timeless history of use.
You have other options to accelerate weight loss.
Instead of using potentially dangerous GLP-1 drugs, here’s what I’d do:
- Uncover mental hurdles/previous life experiences holding you back
- Remove “kryptonite” foods, drinks, and ingredients from the diet
- Consume adequate trace minerals, macros, and micros
- Strategically move with super walking, KAATSU, micro-workouts, sprinting, and super slow strength training
- Build personal resilience and recover like a pro
- Add safer bioregulators, peptides, and small molecules of the future
That leads to sustainable, long-term body recomposition. Fat loss with muscle gain. Plus, your mood and mental health will improve too.
New Gen Weight Loss Drugs: GLP-1 Miracles?
I’m always on the lookout for the best nootropics, ergogenic aids, and novel miracle molecules.
I got excited when I heard about the GLP-1 agonists and immediately begin digging into the research. It just didn’t make sense,
These findings, combined with our results, strengthen the notion that GLP-1 or liraglutide regulate adipogenesis via suppression of apoptosis and stimulation of proliferation.”Regulation of Adipocyte Formation by GLP-1/GLP-1R Signaling
So a drug that increases both the production and survivability of fat cells… helps users lose weight?
I assumed that I was missing something. I talked to several obesity researchers who were equally confused.
For some people, these blockbuster GLP-1 drugs may work great.
After all, obesity is one of the biggest detractors of health and quality of life.
But these injections are certainly no “miracle drugs”. They come at a major cost (financial and potentially health). They come with more questions than answers.
Even if you’re not interested in radically overhauling your diet and lifestyle, you have better options to rapidly transform your body.
I came across this science-y quote that summarizes my primary concern regarding GLP-1,
“So what will happen to folks with years of adipocyte hyperplasia, where individual cell hypertrophy has been suppressed? Their very numerous small adipocytes will, without their uncoupling drug, become enormous. People will become hungry as they develop hypertrophy of all of those lovely tiny insulin-sensitive adipocytes. Oops. It’s gonna be bad, but that’s years down the road.”
Once you begin using these drugs, you’re likely on them for life to avoid a massive fat rebound. But the trials also showed that they only work for about 68 weeks. Then what? What about the other risks?
Time will tell.
For now, I wouldn’t touch semaglutide, liraglutide, or even tirzepatide.
These are just some of my thoughts. What are yours? Let me know in the comments below!