The Transition: Tirzepatide to Retatrutide

Happy Friday!

Before we get into today’s email, I have two quick and exciting announcements:

First: Taylor and I are bringing back our Saturday Morning Coffee Talks! The feedback on these has always been incredible, and I’ve missed connecting with you all in a more relaxed, real-world way.

Mark your calendar for tomorrow (Saturday July 12) at 10 AM EST.

Second: I just dropped a brand new YouTube video today on how to transition from tirzepatide to retatrutide.

This is easily the #1 question I’ve received over the last six months.

I’ve made the switch myself, worked with tons of people doing the same, and there’s a right way to do it that minimizes side effects, maximizes fat loss, and keeps your progress on track.

If you’re thinking about making this change or just curious about the science, this video is for you. Here’s the link:

Why So Many Are Switching

For months now, my inbox, comments, and DMs have been flooded with the same question: “Hunter, how do I switch from tirzepatide to retatrutide? What’s the protocol? Is it safe? Am I going to lose progress?”

There’s a good reason for this.

If you’ve been paying attention to the research, the compounding world, and what’s happening behind the scenes in clinics and research supply companies, you know tirzepatide is increasingly difficult to source reliably.

The FDA has cracked down on compounding pharmacies, driving a ton of folks to the “research only” route.

At the same time, the clinical and anecdotal data around retatrutide has blown everyone away.

Retatrutide is a peptide that fundamentally changes the game for fat loss, metabolic health, and even liver health.

What Makes Retatrutide Different

Most people (even a lot of smart folks in the research world) don’t realize how different retatrutide is from tirzepatide.

Tirzepatide is a “dual agonist,” hitting GIP and GLP-1 receptors.

Retatrutide is a triple agonist.

It hits GIP, GLP-1, and the glucagon receptor.

Let’s break it down:

• Tirzepatide: GIP + GLP-1 agonist. In plain English: boosts insulin secretion, blunts appetite, slows gastric emptying, all while being relatively “gentle” compared to something like semaglutide. Less GLP-1 = fewer GI side effects. That’s why so many people tolerate it better.

• Retatrutide: GIP + GLP-1 + Glucagon. That last bit is what puts retatrutide in a league of its own. Glucagon receptor agonism cranks up energy expenditure and torches liver fat. In a recent study, 8–12 mg a week of retatrutide dropped liver fat by over 80%. That’s life-changing for anyone with metabolic syndrome or non-alcoholic fatty liver disease.

Bottom line: retatrutide builds on what made tirzepatide great and takes it up a notch.

Or three.

The Numbers

In trials, tirzepatide produced 15–22.5% total body weight loss in about 72 weeks at the highest dose (15 mg). That’s 52 lbs lost for a 231 lb person, which was unheard of, at least until retatrutide came along.

Retatrutide? At 12 mg weekly, it produced 24.2% mean weight loss in 48 weeks, and the weight loss curve hadn’t plateaued by the end of the study.

That means people were still losing fat, and the study ended before they even hit their limit.

Not only does retatrutide get you leaner, it gets you there faster.

Plus, it’s more effective at improving A1C, blood pressure, cholesterol, and most importantly, reducing liver fat.

The result is better metabolic health, better blood sugar control, and a fundamentally stronger foundation for longevity.

How to Transition

How do you actually switch?

I’ll cut to the chase: titrate down from your tirzepatide dose over 4–6 weeks, then introduce retatrutide at 2 mg per week.

The details matter, though.

Here’s my “best practice” protocol:

• Week 1: Reduce your tirzepatide dose by 25%

• Week 2: Another 25% reduction

• Week 3: Drop to 50% of starting dose

• Week 4: Down to 2–2.5 mg tirzepatide

• Week 5: Discontinue tirzepatide, start retatrutide at 2 mg/week

Why so cautious?

Because appetite suppression from tirzepatide is strong, stronger than most people expect.

If you stop cold turkey, your appetite (and old cravings) will come roaring back.

But by gradually reducing your dose, you help your body adjust, keep weight loss moving, and start retatrutide from a place of receptor sensitivity (critical for seeing continued progress).

What to Expect

What happens when you switch?

Most people are surprised to find fewer side effects when starting retatrutide, even at 2 mg/week.

If you’ve tolerated tirzepatide well, retatrutide will feel easy, though you might notice a temporary uptick in hunger.

This is because you’ve just come off a high dose of a medication with major appetite suppression.

Pro tip: If you’re worried about GI issues, start with lower doses (1–2 mg) and eat smaller, lower-fat meals.

High fat diets + these peptides = more nausea for a lot of people.

Some people report a slight increase in heart rate with retatrutide, thanks to that glucagon effect.

It’s almost never a problem, but it’s worth noting.

And no, the glucagon agonism won’t spike your blood sugar because the GLP-1 and GIP balance that out beautifully.

Dosing Smarter

One of my biggest frustrations is seeing people take more than they need.

I’ve seen people on 20–30 mg of tirzepatide per week.

More is not better!

Peptides, especially these, work best at the minimum effective dose.

Start low.

Use 2 mg of retatrutide for 2–3 weeks.

If you need to, then titrate up.

Build your baseline, let your body adapt, and pay attention to how you feel.

If you ever want to “stack” the two for a brief crossover (say, 1 mg of each for 2–4 weeks), that’s reasonable, but always listen to your body and track your response.

Fat Loss Pathways

It’s easy to get obsessed with GLP-1s, GIP, and the “peptide of the month.”

But don’t forget: there are countless pathways for fat loss.

Nutrition, movement, sleep, stress, mitochondrial health, and all the other levers we talk about every week in this community.

Peptides are powerful tools, but not magic.

I’m always going to teach and remind you that the best approach is holistic.

Optimize your hormones, stack your lifestyle, use these advanced molecules as accelerators.

Final Thoughts

This transition is just one example of the kind of real, practical, evidence-backed help I want to deliver to you, whether it’s in these emails, on YouTube, or during our Saturday Coffee Talks.

I read every comment, even if I can’t reply to all. Your support means the world to me (and Taylor).

It’s your curiosity and willingness to push boundaries that drive everything I do.

If you’re considering the switch, let me know how it goes!

Best,

Hunter Williams

P.S.