Introduction
What is this buzz about peptides?
Is everybody using them but me? You may be asking yourself that. I was several years ago. Let me take you down the path that changed my thinking.
GLP-1 drugs have a 40-year scientific history, but the current boom arrived with Novo Nordisk's once-weekly semaglutide.
- Ozempic was approved in 2017 for diabetes.
- Wegovy (the same drug but administered at a larger dose) was approved in 2021 for obesity.
That turned a niche diabetes drug into a huge global market obesity treatment.
GLP-1 was first identified in the 1980s and 1990s. It was described as an incretin hormone, meaning it boosts insulin secretion and reduces appetite. That led to the idea of GLP-1 receptor agonists (GLP-1RAs) as a new class of drugs for diabetes.
The first marketed GLP-1RA was exenatide (Byetta), which was derived from Gila monster venom. Imagine that, a little creepy? The peptide was exendin-4. It was approved by the FDA in 2005 and proved the concept that GLP-1 mimetics could safely treat type 2 diabetes.
Novo Nordisk's huge success impacted not only the company finances but the economy of Denmark (and Norway as well). Some of the money flowed to the country's sovereign fund, and ordinary citizens benefited too.
In the U.S., shortages opened the door for compounded semaglutide. The argument was that these peptides are naturally occurring and should not be protected by patents. Compounding pharmacies could obtain the peptides and make their own products for consumers.
This developed into a huge market. Compounded GLP-1s were huge. In 2025, big pharma manufacturers had ramped up production, and the FDA's effort to shut down these upstarts began. We do not know how this will play out. It is hard to put a genie back in the bottle.
What are peptides?
Peptides are short strings of amino acids usually defined as 4 or 5 amino acids up into 40-50 amino acid chain. Some peptide are very small and less than 4 or 5 amino acids in length. These are usually classified as bioregulators. They were extensively studied decades ago by the Russians and I will get into that history in another article because I believe that was really the incentive for this boom in interest in peptides.
How do they work? Cells have receptors on their surfaces especially but also inside the cell. Molecules can attach to these receptors and trigger changes inside the cell. Think along the line of a switch that gets turned on or off. Most peptides function like hormones. They are messenger molecules that direct action.
Insulin is actually a peptide. Think about the cascade of changes that insulin triggers.
Why did GLP-1s get so famous?
I remember watching some of the incredible transformations with early users of Ozempic, Wegovy and other new drugs for weight loss. I also remember a few of the horror stories. Rare, but they happened nevertheless.
This class of drugs became household topics for discussion due to their huge success as weight loss drugs. Ozempic is a GLP-1. By now there are GLP-2s and GLP-3s as well.
Wegovy was the GLP-1 marketed for weight loss. It was a higher dose. Everyone wants instant results, and early testing showed more weight loss with higher doses. That was the push: higher doses for faster results.
And they were outrageously expensive, especially if your insurance did not cover them.
Do you see a problem here?
The problem: higher doses, more side effects
Is it a surprise that with high doses came more side effects? Everyone has heard some of the horror stories. Many were not adequately prepared or educated for the possible side effects of the medicine.
With the resulting loss of appetite, and the overall poor diets of the participants, people did not just lose fat. They also suffered significant muscle loss. Their protein intake and exercise regimens were not sufficient enough to offset the huge drop in calories.
Some had markedly decreased movement in their gut. The medical term for that is hypoperistalsis. Peristalsis is the normal smooth muscle contraction that pushed food through the gut. In severe cases, their guts shut down. Some needed surgery to correct.
In addition to loss of appetite for food, there was a noticed loss of appetite for addictions, including gambling behavior. I believe the term is anhedonia, or the loss of pleasure. Food simply did not give the pleasure it had in the past. Some lost pleasure overall and were described as depressed.
People were not prepared for their overall reaction to these drugs. These side effects were often dose-dependent.
What peptides are really doing
This signaling function of peptides is complex and needs study and research. It is a chain reaction, where the introduction of one peptide can trigger a symphony of downstream activity.
Since they are such powerful molecules, peptides are not to be taken lightly. You and your health care provider should approach them with understanding. You are responsible for conducting the concert. It's your body.
A better approach: microdosing and the whole picture
This is my belief after years of study. Dose is very immportant with these powerful molecules. Many times they may need to be administered in combination. We've learned over the years that they can be administered in microdosing regimens. When you are microdosing with a fraction of the usual therapeutic dose (maybe 5%) as defined by the big Pharma companies, you can achieve benefits and greatly limit the risk of side effects! Think of gaining some of the benefits and avoiding many of the side effects. Certainly it won't be as rapid a weight loss. More subtle. Remember getting healthy is a marathon and not a sprint.
The benefits can be huge, not only in weight loss but also in reproportioning body composition. But in this symphony, we need to pay attention to preserving muscle mass, and even increasing it. Muscle mass is associated with longevity.
This can be easy to achieve if we keep the entire picture in focus. We'll discuss the specifics of this in later articles.