What do you think about retatrutide?

Retatrutide has been making headlines lately, mainly because of its phase 3 clinical trial results. 

Not surprisingly, I get questions about it every day.

I've intentionally avoided covering it for the reasons I'll explain below, and instead stay focused on what's actually working for my clients.

But with so many questions about retatrutide, I figured it was time to explain my perspective, and have a place to send people in the future when they ask me, "What do you think about retatrutide?"

My short answer is this: Based on what I’ve seen in clients and heard from followers, and the current reality of access, this is one of those situations where excitement is running ahead of common sense.

Let’s walk through what retatrutide actually is, how it differs from semaglutide and tirzepatide, why so many people, especially women, report feeling awful on it, and why I’m still steering clients toward FDA-approved options for now.

What Retatrutide Actually Is

Retatrutide is a triple-agonist medication.

That means it activates three receptors at once:

• GLP-1 (glucagon-like peptide-1)

• GIP (glucose-dependent insulinotropic polypeptide)

• Glucagon

Semaglutide targets GLP-1 only. Tirzepatide targets GLP-1 and GIP.

Retatrutide adds glucagon signaling to the mix.

That third pathway is the reason it looks so powerful in early obesity trials. Glucagon increases energy expenditure, fat mobilization, and metabolic drive.

In theory, it helps the body burn more while eating less.

And in tightly controlled trials focused on significant weight loss, the results have been eye-opening.

But physiology doesn’t happen in a vacuum.

The Part Most People Miss: Glucagon Is Stimulating

Glucagon isn’t just a “fat-burning” signal.

It’s a stress-associated hormone.

It raises blood glucose. It increases metabolic output. It pushes the nervous system toward a more activated state.

That’s not inherently bad, but it matters who is using it and why.

Obesity and lethary often go hand in hand. When you're severely overweight, you don't feel energetic enough to move more. Because you don't move enough, you make weight gain and insulin resistance worse.

So if by stimulating glucagon, you feel more energized and feel the need to move, your increased activity can help accelerate weight loss. It's like giving your metabolism a jump start.

But most of the people following me and working with me aren’t after extreme weight. They're also more sensitive to stimulating their nervous systems. They’re looking for:

• Improved metabolic health

• Better insulin sensitivity

• Reduced inflammation

• Appetite normalization

• Longevity and resilience

• Calm, sustainable fat loss

• Increased resilience and a more balanced nervous system response

And this is where retatrutide starts to show its cracks.

Why So Many People Feel “Wired and Awful” on Retatrutide

This isn’t theoretical for me.

I’ve had dozens of people reach out, both clients and followers, who experimented with retatrutide through research channels.

The pattern is remarkably consistent.

They don’t say, “I had mild nausea.”

They say things like:

• “I felt anxious and edgy all the time.”

• “My sleep fell apart.”

• “My heart felt like it was racing.”

• “I felt overstimulated but exhausted.”

• “It felt like too much.”

And notably, this shows up far more often in women.

That makes sense physiologically.

Women are more sensitive to:

• Nervous system overstimulation

• Catecholamine shifts

• HPA-axis stress

• Blood sugar volatility

When you layer glucagon signaling on top of already stressed systems, you don’t get balance, you get noise.

This is something I do not see with properly dosed tirzepatide, especially at microdose levels.

The Other Problem: How Retatrutide Is Currently Accessed

Here’s the other part I feel strongly about.

Retatrutide is not FDA-approved.

That means the only way to obtain it right now is as a research-grade peptide.

And this is where things get questionnable.

There are far more raw material suppliers globally than there are facilities that meet FDA-audited pharmaceutical manufacturing standards.

There are thousands of suppliers worldwide capable of producing:

• API precursors

• peptide fragments

• research-grade peptides

• bulk chemical intermediates

That alone doesn’t make a product unsafe, but it also doesn’t make it pharmaceutical-grade.

Only a small subset of facilities globally are equipped to:

• manufacture finished drug substances intended for human use, and

• operate under FDA-inspected, FDA-enforced current Good Manufacturing Practices (cGMP)

That distinction is critical.

FDA auditing is not automatic and not universal. It only applies when:

• a manufacturer is producing drugs specifically intended for human use, and

• that product is part of an FDA-regulated drug supply chain, such as an NDA, ANDA, BLA, or a registered outsourcing facility.

Most peptide and raw material suppliers around the world:

• are not registered drug manufacturers

• are not routinely inspected by the FDA

• may follow internal or ISO-style GMP processes, but not FDA-enforced pharmaceutical cGMP

That doesn’t mean every research-grade product is dangerous. It means the oversight, accountability, and consistency are fundamentally different.

And when a compound like retatrutide is not yet FDA-approved, it cannot legally move through the regulated pharmaceutical pathway. By definition, it exists outside the systems designed to ensure:

• consistent purity

• verified dosing

• stability testing

• post-market safety tracking

Even a promising molecule deserves a manufacturing process that matches its potential.

That alone is reason enough for me to say “not yet.”

How This Differs From Tirzepatide in the Real World

Tirzepatide has been a very different experience.

Yes, it’s powerful, but it’s also surprisingly calming for many people.

At the right dose, I routinely see:

• Improved blood sugar stability

• Reduced food noise

• Better sleep

• Lower inflammation

• Improved nervous system tone

And importantly, fewer reports of anxiety or overstimulation.

That’s why so many of my clients use tirzepatide not as a “weight loss drug,” but as a metabolic regulator, especially when dosed far below what’s used in obesity trials.

Retatrutide, by contrast, feels like it’s pushing the gas pedal harder than most people’s systems can tolerate.

Who Retatrutide May Be Ideal For, Eventually

To be clear, I’m not anti-retatrutide.

Once it’s FDA-approved, pharmaceutical-grade, and properly studied across diverse populations, I think it may be an excellent tool for:

• Individuals with significant obesity

• Those who have failed other GLP-1 approaches

• Carefully monitored, short-to-medium-term weight loss interventions

But that’s a very different use case than, “I want metabolic health, longevity, and to feel better.”

Right now, those are being lumped together, and they shouldn’t be.

My Current Recommendation (And Why)

If someone asks me today, “What are your thoughts on retatrutide?”

My answer is this:

• It’s promising, but premature

• The current access model carries unnecessary risk

• It appears too stimulating for many people, especially women

• I don’t see better outcomes than tirzepatide, only more side effects

For now, I recommend finding a doctor or the right telehealth company to hep you with:

1. Tirzepatide (ideally, at microdose levels for health and longevity)

2. Semaglutide, if tirzepatide isn’t accessible

These are FDA-approved, well-studied, and far more predictable in how people respond.

Leaving Room to Be Wrong (On Purpose)

If retatrutide becomes FDA-approved and:

• Dosing strategies improve

• The stimulation issue turns out to be less of an issue than I'm seeing now

• Long-term safety data supports broader use

I’ll happily update my position.

That’s how science should work.

But until then, I’m not willing to trade reliability, safety, and real-world tolerability for hype.

Progress isn’t about chasing the newest thing.

It’s about choosing the right tool at the right time for the right person.

And right now, for most people focused on health, resilience, and sustainable fat loss, retatrutide just isn’t that tool yet.