10 Dangers of GLP-1 Weight Loss Drugs (Liraglutide, Semaglutide, Tirzepatide)

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.

Temporary

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.

Muscle loss

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.

Expensive

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.

Cancer

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 is 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.

Unpleasant symptoms

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:

• Nausea
• Diarrhea

Perhaps the lack of cravings and appetite stems from the inability to hold food down.

Even among users who get the dose right, these side effects are the norm.

Biomarker concerns

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.

Stomach paralysis

Six months after I first published this article, new research came out highlighting additional side effects.

One such study of 5,000 GLP-1 users, published in JAMA, found an increased risk of stomach paralysis, pancreatitis, gastroparesis, and bowel obstruction [R].

And this wasn’t the first research paper to show that possibility [R].

Many of the headlines confuse the public by portraying the relative risk instead of the absolute risk. Nonetheless, this side effect should weigh into decision-making.

Organ failure & more

When discussing the potential side effects, where’s the best place to look?

Well, a case study published on PubMed details two accounts of organ failure (kidneys) from GLP-1 agonist drugs [R]. Yet a table later in that paper also lists 500+ cases of kidney damage, broken down by GLP-1 drug.

But that’s not what I am referring to. The best place to learn about the side effects of these drugs is directly from the official website of the manufacturers.

These are the official (serious) potential side effects of Ozempic, from their website [R]:

• Cancer
• Kidney failure
• Thyroid tumors
• Gallbladder dysfunction
• Pancreatitis
• Vision disturbances
• Hypoglycemia

Then in November 2023, a new study came out titled: As Semaglutide’s Popularity Soars, Rare but Serious Adverse Effects Are Emerging. It further explores some of these [R].

And those are just the currently known serious side effects.

Unknown consequences

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.