If you've been following the GLP-1 weight loss space, you've heard of Ozempic, Wegovy, and Mounjaro. You may have heard of semaglutide and tirzepatide — the compounded versions that have made these drugs accessible at a fraction of the brand-name price. But there's a third generation of this drug class that most people haven't heard of yet: GLP-3, also known as retatrutide.
The clinical data behind it is striking. Phase 2 trial results published in the New England Journal of Medicine in 2023 showed that retatrutide produced an average body weight loss of 24.2% — more than any other weight loss compound ever studied in a randomized clinical trial. For context, that's a 260-pound person losing 63 pounds.
Here's what GLP-3 actually is, how it works, and why Thinnex is one of the only providers currently offering access to it.
The Short Version: What Makes GLP-3 Different
GLP-1 drugs like semaglutide target one receptor. Tirzepatide targets two (GLP-1 and GIP). Retatrutide — GLP-3 — targets three receptors simultaneously: GLP-1, GIP, and glucagon.
That third pathway — the glucagon receptor — is what makes retatrutide categorically different. While GLP-1 and GIP work primarily through appetite suppression and insulin regulation, glucagon receptor agonism directly increases energy expenditure. Your body burns more calories at rest. It's not just eating less — it's also burning more.
GLP-1 Receptor
Reduces appetite, slows gastric emptying, regulates blood glucose through insulin stimulation
GIP Receptor
Enhances insulin secretion, reduces glucagon levels post-meal, improves fat metabolism in adipose tissue
Glucagon Receptor ★
Directly increases energy expenditure (calories burned at rest) and promotes lipolysis — the breakdown of stored fat
The Clinical Trial Data
The key study was a Phase 2 randomized controlled trial of retatrutide published in the New England Journal of Medicine in June 2023. 338 adults with obesity (average BMI 37.3) were randomized to receive retatrutide at various doses or placebo over 24 weeks.
At the highest dose (12 mg), participants lost an average of 17.5% of their body weight at 24 weeks, with a projected 24.2% loss by 48 weeks based on the treatment trajectory at study end. The study was not powered to run to 48 weeks, but the slope of weight loss had not plateaued at 24 weeks — suggesting continued loss beyond the study window.
Phase 2 trials are designed to assess safety and dose-ranging, not to definitively establish efficacy. Phase 3 trials (longer, larger, and more rigorous) are underway for retatrutide toward potential FDA approval of a brand-name product. The compounded version available through Thinnex is retatrutide prepared by a licensed 503A compounding pharmacy under a valid physician prescription — not an FDA-approved product.
How It Compares Head-to-Head
| Drug | Receptors | Avg. Weight Loss | Trial Duration | FDA Status |
|---|---|---|---|---|
| GLP-3 (Retatrutide) | GLP-1 · GIP · Glucagon | 24.2% (projected) | 48 weeks (projected) | Phase 3 trials underway |
| Tirzepatide (Zepbound) | GLP-1 · GIP | 22.5% | 72 weeks | FDA-approved (brand) |
| Semaglutide (Wegovy) | GLP-1 | ~15% | 68 weeks | FDA-approved (brand) |
Who Is GLP-3 For?
GLP-3 (retatrutide) is most appropriate for patients who:
- Have tried semaglutide and want stronger results
- Have tried tirzepatide and want to maximize their outcomes
- Are starting their weight loss journey and want the most advanced option available
- Have a significant amount of weight to lose (generally 50+ lbs) and want the highest-efficacy peptide option
- Want the additive energy-expenditure effect of the glucagon pathway, not just appetite suppression
Like all GLP-1 class medications, retatrutide should not be used by patients with a personal or family history of medullary thyroid carcinoma, Multiple Endocrine Neoplasia syndrome type 2 (MEN2), or by pregnant women. A thorough medical history review by a licensed provider is required before starting treatment.
Side Effects: What to Expect
The side effect profile of GLP-3 in Phase 2 trials was consistent with the broader GLP-1 drug class. The most common adverse effects were gastrointestinal:
- Nausea (most common, typically mild and dose-dependent)
- Vomiting (less common)
- Diarrhea
- Constipation
- Decreased appetite (this is the therapeutic effect, but can be uncomfortable early on)
Most GI side effects diminished as the body adjusted to the medication and stabilized during the titration phase. The trial reported no significant difference in serious adverse events versus placebo at the studied doses.
The dose titration protocol for retatrutide — starting low and escalating gradually over the first 8–12 weeks — is designed specifically to minimize these early GI effects.
Why Most Programs Don't Offer It
There are two reasons most telehealth platforms haven't added retatrutide to their formularies:
1. Complexity. Retatrutide requires a more detailed clinical protocol than semaglutide or tirzepatide. The titration schedule is more nuanced, and providers need to be specifically trained on its pharmacology. Most large-volume GLP-1 platforms optimize for throughput — they run high volumes of patients on well-established protocols, not the most advanced options.
2. Awareness. Retatrutide doesn't have a brand-name product (yet). Ozempic and Mounjaro dominate consumer awareness. Most patients arriving at telehealth platforms are asking for "semaglutide" or "tirzepatide" — not a compound they've never heard of. That demand pull hasn't arrived yet. When it does, access through licensed compounding will be the only affordable path for most patients.
At Thinnex, we made the decision early to include retatrutide in our formulary precisely because of its clinical differentiation — and because we believe our patients deserve access to the most effective tools available, not just the most marketed ones.
Interested in GLP-3?
Our board-certified physicians evaluate whether retatrutide is appropriate for your individual medical history. Complete your intake and find out if you qualify — it takes under 5 minutes.
Learn About GLP-3 at Thinnex →The Bottom Line on GLP-3
Retatrutide is not hype. The Phase 2 data is real, it was published in the most prestigious medical journal in the world, and the mechanism — targeting three separate receptor pathways — provides a scientifically coherent explanation for why the results exceed what single and dual agonists have achieved.
It is not FDA-approved as a finished drug product, and the compounded version comes with the same caveats as all compounded medications. But for patients who want access to the leading edge of metabolic medicine, GLP-3 represents a genuine step forward — and Thinnex is one of the few places where you can currently access it.
→ Also read: 7 Best GLP-1 Programs in 2026 — Ranked & Compared
→ Also read: Semaglutide vs. Tirzepatide — Which Is Right for You?