The Big Three: GLP-1 Peptides Explained
The metabolic peptide space has exploded with three major players: semaglutide (Ozempic/Wegovy), tirzepatide (Mounjaro/Zepbound), and retatrutide (the newest triple agonist). Each targets different receptor combinations, and the peptide community has strong — and often conflicting — opinions on which is best.
This guide breaks down the science, the community experience, and the practical differences to help you understand each option.
How They Work
The fundamental mechanism behind all three is incretin mimicry. Incretins are gut hormones that regulate appetite and metabolism. These peptides mimic those hormones to suppress hunger, improve glucose regulation, and promote fat loss.
Semaglutide: The Single Agonist
Semaglutide targets GLP-1 receptors only (single incretin). It was the first in this class to gain mainstream attention through the brands Ozempic and Wegovy.
How it works:
- Mimics GLP-1 to signal fullness to the brain
- Reduces appetite and cravings
- Slows gastric emptying (food stays in the stomach longer)
- Improves glucose efficiency and insulin sensitivity
Tirzepatide: The Dual Agonist
Tirzepatide targets both GLP-1 and GIP receptors (dual incretin), marketed as Mounjaro and Zepbound. It was the next evolution after semaglutide.
How it works:
- Activates GLP-1 receptors for appetite suppression (like semaglutide)
- Also activates GIP receptors for enhanced fat metabolism
- More powerful appetite suppression than GLP-1 alone
- May offer additional benefits including neuroprotection and improved bone density
Retatrutide: The Triple Agonist
Retatrutide targets GLP-1, GIP, and glucagon receptors (triple incretin). It's the newest and most potent of the three.
How it works:
- All the benefits of GLP-1 and GIP activation (like tirzepatide)
- Adds glucagon receptor activation for active fat burning
- Rather than just suppressing appetite passively, glucagon actively promotes fat oxidation
- Phase 2 trials showed up to 82% reduction in liver fat
The Community Debate
The peptide community is far from unanimous on which is best. Here's what real users are saying:
The Semaglutide Camp
Some experienced users argue semaglutide is sufficient for most people. One user who tried all three reported that semaglutide was the only one that "completely knocked out hunger." Their argument: tirzepatide and retatrutide are more expensive without proportionally better results for the average person.
Semaglutide is also the most well-studied, with the longest track record and the most clinical data on safety and efficacy.
The Tirzepatide Camp
Tirzepatide supporters argue it offers a better experience overall. One user reported losing 91 lbs over a year and a half on tirzepatide. Multiple users note that tirzepatide provides stronger appetite suppression with better muscle retention compared to semaglutide.
A common complaint about semaglutide is that users "look like a stick" — losing both fat and muscle. Tirzepatide users report being able to retain and even gain muscle mass while losing fat, making it better for body recomposition.
The Retatrutide Camp
Retatrutide enthusiasts point to the Phase 2 clinical trial data showing it as the most effective for total weight loss. Because it adds glucagon activation, the body actively burns fat rather than relying solely on eating less.
Users also note that retatrutide is superior for body recomposition — the body burns fat more efficiently while retaining more muscle mass.
Dosing Protocols
Semaglutide
- Starting dose: 0.25 mg/week
- Maintenance dose: Gradually increase to 1.0-2.4 mg/week
- Administration: Once weekly subcutaneous injection
- Titration: Increase every 4 weeks as tolerated
Tirzepatide
- Starting dose: 2.5-5 mg/week
- Maintenance dose: Gradually increase to 10-15 mg/week
- Administration: Once weekly subcutaneous injection
- Titration: Increase every 4 weeks as tolerated
Retatrutide
- Starting dose: 1 mg/week
- Maintenance dose: Up to 12 mg/week (based on clinical trial protocols)
- Administration: Once weekly subcutaneous injection
- Titration: Increase every 4 weeks as tolerated
Side Effects Comparison
All three share similar GI-related side effects, but severity varies:
Semaglutide (Mildest)
- Nausea: 20-30% of users
- Generally the most tolerable option
- GI effects tend to decrease after the first few weeks
- Best option for those sensitive to side effects
Tirzepatide (Moderate)
- Nausea: 30-40% of users
- Slightly more GI disturbance than semaglutide
- Some users report constipation or diarrhea
- Side effects typically manageable with proper titration
Retatrutide (Most Intense)
- Potentially more severe GI effects due to glucagon activity
- Glucagon activation can cause additional metabolic effects
- Less clinical data available on long-term side effects
- Requires more careful dose titration
Which Should You Choose?
Choose Semaglutide if:
- You're new to GLP-1 peptides and want the most studied option
- You have a moderate amount of weight to lose (10-30 lbs)
- You're sensitive to medication side effects
- Budget is a primary concern (generally the cheapest option)
- You want the longest safety track record
Choose Tirzepatide if:
- You want stronger appetite suppression than semaglutide
- Muscle retention is important to you (body recomposition)
- You have a significant amount of weight to lose (30+ lbs)
- You've tried semaglutide and want something more effective
- You're willing to pay more for potentially better results
Choose Retatrutide if:
- You want the most aggressive fat loss approach
- Active fat burning (not just appetite suppression) appeals to you
- You're interested in liver fat reduction
- You're comfortable being an early adopter with less long-term data
- Body recomposition is your primary goal
Pricing Through Peptard Group Buys
Group buying makes these expensive peptides significantly more accessible:
- Semaglutide 5mg Kit (10 vials): ~$120 via Peptard group buys
- Tirzepatide 30mg Kit (10 vials): ~$195 via Peptard group buys
- Tirzepatide 60mg Kit (10 vials): ~$300 via Peptard group buys
- Retatrutide 24mg Kit (10 vials): ~$250 via Peptard group buys
Compare these to pharmacy prices: Wegovy (semaglutide) retails at ~$1,300/month and Zepbound (tirzepatide) at ~$1,000/month.
The New Frontier
The GLP-1 space continues to evolve. Some forums have discussed experimental compounds like "Bioglutide" that reportedly targets four receptors (GLP-1, GIP, glucagon, plus IGF-1), though community members have flagged this as unverified. Oral GLP-1 formulations are also in development but not yet widely available in research-grade form.
For now, the Big Three — semaglutide, tirzepatide, and retatrutide — represent the established options with the most data and community experience behind them.
Frequently Asked Questions
Can I switch between semaglutide, tirzepatide, and retatrutide?
Yes, but allow a washout period between switching (typically 2-4 weeks). Don't overlap or combine multiple GLP-1 agonists.
Will I regain weight after stopping?
This is the most common concern. Most users report appetite returning after discontinuation. The community consensus is to use the peptide to reach your goal weight while building sustainable eating habits.
Do these affect muscle mass?
Semaglutide has the most reports of muscle loss. Tirzepatide and retatrutide appear to preserve muscle better. Resistance training while using any GLP-1 agonist is strongly recommended.
How do I store these peptides?
All three follow standard peptide storage: lyophilized powder at -20°C, reconstituted with BAC water and refrigerated at 2-8°C, used within 30 days of reconstitution. For complete details, read our Peptide Storage Guide.
Make sure to verify your peptide purity before use, and browse current GLP-1 group buys on Peptard to save on your next order.
This article is for informational and research purposes only. Semaglutide, tirzepatide, and retatrutide are prescription medications in their branded forms. Research peptide versions are sold for laboratory use only. Always follow applicable regulations.