GLP-3 Explained: Triple-Agonist Weight-Loss Drugs

Short answer: When people say “GLP-3,” they usually mean a new class of triple-agonist medicines that activate GLP-1, GIP, and glucagon receptors at once. The leading candidate is retatrutide. In a 48-week phase 2 study, the highest dose produced about 24% average weight loss, with continued loss at the study’s end (not yet FDA-approved) (NEJM phase 2 trial; 2024 meta-analysis).

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TL;DR (for “GLP-3” searchers)

• There’s no human hormone called “GLP-3.” The term online typically refers to a triple-agonist drug that targets three receptors: GLP-1, GIP, and glucagon. The most advanced example is retatrutide.
• In a phase 2 obesity trial, retatrutide 12 mg led to a mean −24.2% weight change at 48 weeks, and participants were still losing weight at week 48 (NEJM).
• Common side effects resemble GLP-1 medicines (nausea, vomiting, diarrhea, constipation) and are typically dose-related; modest heart-rate increases were observed. Slow titration helps tolerability (NEJM).
• Retatrutide is investigational. Phase 3 trials are underway. A consumer timeline cited by GoodRx suggests potential FDA review around 2027 (subject to change) and warns about counterfeit products (GoodRx).
• Use a DEXA scan to confirm you’re losing fat (especially visceral fat) while preserving lean mass during any weight-loss program. Start here: DEXA for visceral fat and preventing muscle loss on Ozempic.

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What “GLP-3” Really Means (and why it’s exciting)

Online, “GLP-3” has become shorthand for a triple-agonist approach to metabolic disease. These drugs are designed to pull three powerful levers at once:

• GLP-1: curbs appetite, slows gastric emptying, improves post-meal glucose control.
• GIP: works alongside GLP-1 on insulin and appetite signaling.
• Glucagon: in this context may increase energy expenditure and influence fat metabolism.

The best-studied candidate so far is retatrutide. In a double-blind, randomized, placebo-controlled phase 2 trial in adults with obesity, weekly retatrutide produced large, dose-dependent weight loss through 48 weeks compared with placebo (NEJM phase 2). A 2024 systematic review pooling randomized trials also found significant weight and metabolic improvements with an acceptable safety profile (PMC meta-analysis). In that phase 2 trial, responder rates were high (e.g., many participants achieved ≥15% loss), and cardiometabolic markers like blood pressure and lipids improved while many with prediabetes reverted to normoglycemia.

Safety profile and side-effect management

The side effect profile is similar to other GLP-1 based medications:

• GI symptoms: nausea, vomiting, diarrhea, constipation—often during dose escalations, typically mild to moderate.
• Heart rate: small resting HR increases, peaking around week 24 in the phase 2 study.

Practical tips to improve tolerability:

• Start low, go slow: Gradual titration is key; many clinics pace increases every ~4 weeks. Our Retatrutide Dosing Guide provides a full titration schedule.
• Favor smaller, lower-fat meals during escalation; sip fluids steadily; stay upright for 30 minutes after eating. For more strategies, see our guide on Managing Side Effects.

Important safety notes:

• Retatrutide is investigational; any use outside trials is unapproved.
• Beware counterfeit retatrutide products marketed online; GoodRx notes the FDA warns against such sales because purity, dose, and safety are unknown (GoodRx).

How does “GLP-3” compare with today’s options?

Note: These figures come from different trial designs and durations; they’re not head-to-head comparisons unless specified. Always review individual study details.

Access, cost, and timeline

• Regulatory status: Retatrutide is in Phase 3. Consumer timelines are estimates and can shift. GoodRx currently projects a potential 2027 approval if trials and reviews go as planned (GoodRx).
• Availability today: Only through clinical trials. Avoid gray-market/“research” sources.
• Coverage & pricing: Unknown until after regulatory decisions.

Protecting muscle and tracking visceral fat (why DEXA matters)

Rapid weight loss can include some lean-mass loss. Preserving muscle protects your metabolism and performance. To preserve muscle, it’s recommended to pair medication with protein and resistance training, and track your composition with DEXA so you know you’re losing fat, not muscle:

• Start with our primer on preventing muscle loss on Ozempic.
• See how DEXA estimates visceral fat (VAT) and why VAT loss matters: DEXA for visceral fat.
• New to DEXA? Here’s our complete scan guide.

A common cadence for rescanning is every 8–12 weeks during a medication or nutrition phase to confirm fat loss, lean-mass preservation, and VAT reduction.

FAQs

Is “GLP-3” a real hormone?
No. Humans have GLP-1 and GLP-2. Online, “GLP-3” usually means a drug that stimulates three receptors (GLP-1, GIP, and glucagon). Retatrutide is the leading example.

How much weight can these triple-agonists produce?
In a key phase 2 trial, the highest dose of retatrutide led to an average weight loss of about 24.2% at 48 weeks, and participants were still continuing to lose weight.

Are they FDA-approved?
Not yet. Phase 3 trials are ongoing. GoodRx projects possible FDA review around 2027 (GoodRx).

What side effects should I expect?
The most common side effects are dose-related GI issues like nausea and diarrhea, plus modest increases in heart rate. Slow dose increases help manage them.

How are doses escalated?
Clinics often increase weekly doses every ~4 weeks, adjusting for tolerance. See our overview of Retatrutide Dosing in Clinical Trials.

Can I get retatrutide now?
Only within clinical trials. Avoid online sellers. GoodRx warns about counterfeit risk (GoodRx).

How do I make sure I’m losing fat, not muscle?
The best strategy combines adequate protein intake, resistance training, and body composition tracking with DEXA. Learn more in our guides on lean-mass preservation and visceral fat tracking.

The bottom line

“GLP-3” is the internet’s nickname for triple-agonist drugs like retatrutide. Early trials show remarkable weight loss—up to 24.2% at 48 weeks—with a side-effect profile similar to GLP-1–based therapies and improvements in cardiometabolic markers. These medicines are not yet approved. While the field advances, you can act now: pair high-impact nutrition and training with DEXA tracking to protect muscle, reduce visceral fat, and make your results data-driven.

Ready to get a precise baseline? Book a BodySpec DEXA scan.