Retatrutide vs. Semaglutide: Switching Guide in 2025

Lately, it feels like I've become the go-to at the gym for all things peptide-related – chalk it up to my passion for everything weightlifting, strength, and optimized performance. In an effort to not recreate the writing wheel each week, I'm laying it all out here.

Enter the leader of the pack: Semaglutide (you might know it as Ozempic). It's had a good run, but new studies tell us its inferior. So who is the new top dog? Retatrutide. Stick around as I unravel the details of this trending transition.

Before I go on, let me make 2 things extremely clear!
1. I am not a medical professional. This post is for informational purposes only and is based on studies and anecdotal experiences; it is not medical advice. Always consult your healthcare provider before making any medication changes.
 2. I do not currently take either peptide. Years ago, I tried Sema briefly but stopped due to a decline in strength as my calorie intake dropped. I have not used Reta, though I know many who have for specific needs. Always consider individual goals and consult professionals before use.

Converting from Semaglutide to Retatrutide

Comparison: Weight Loss Efficacy (Phase II Studies)

• Retatrutide: 22.8 - 24.2% average body-weight loss at 48 weeks (In trials for women: up to 29% weight reduction)

• Semaglutide: 14.9% average weight reduction at 68 weeks

Metabolic Benefits

• HbA1c Reduction: Retatrutide shows up to –2.02 % HbA1c, indicating strong glycemic control

• Liver Fat Reduction: Phase II study: 1 mg to 12 mg retatrutide reduced liver fat by –51% to –86% over 48 weeks, vs. –4.6% for placebo

How and Why? Mechanistic Advantages

Retatrutide's Triple Agonism: Targets GLP 1, GIP, and glucagon receptors—broader metabolic effects than semaglutide, a single GLP 1 agonist.

How to Switch: Starting Dose of Retatrutide

When transitioning from semaglutide, it’s important to reset your expectations and start low, regardless of your current semaglutide dose. That’s because retatrutide is a different molecule with a broader receptor profile and potentially stronger effects.

Recommended Retatrutide Starting Dosage:

• The standard is to start at 0.5 mg once weekly. If you are on a high dose of Sema/Ozempic currently, I have seen several people switch straight to 1mg or 2mg of Reta with no issues.

• Titrate up slowly every 2-4 weeks based on tolerance (e.g., nausea, appetite changes), just like you did with semaglutide

• Common titration schedule (weekly dosage): 0.5 mg → 1 mg → 2 mg → 4 mg → 8 mg → 12 mg (max dosage – maintenance dosage)

Even if you were on a higher dose of semaglutide (e.g., 1 mg or 2.4 mg weekly), do not start retatrutide at a high dose. Begin at the lower dose to minimize side effects and let your body adjust.

Summary: Why to Consider Switching?

• Greater weight loss: Early trials show up to 24%+ body weight reduction

• Broader metabolic impact: Targets three key hormones for appetite and energy

• Next-gen innovation: May become the most powerful tool yet for obesity and diabetes

Always make the switch under medical supervision to adjust for side effects and individual needs.

This post is for educational purposes only and not medical advice. Consult your healthcare provider before making any medication changes.