What Are GLP-1 Peptides?
GLP-1 (glucagon-like peptide-1) receptor agonists are a class of peptides that mimic incretin hormones to regulate blood sugar, slow gastric emptying, and reduce appetite. Originally developed for type 2 diabetes, they became a cultural phenomenon after demonstrating significant weight loss in clinical trials. Three compounds dominate this space — each targeting a different number of receptors.
GLP-1 peptides have reshaped both the pharmaceutical and compounding pharmacy landscapes. Understanding the differences between semaglutide, tirzepatide, and retatrutide — and how to source each — is essential for anyone in this market.
The Three GLP-1 Peptides at a Glance
| Property | Semaglutide | Tirzepatide | Retatrutide |
|---|---|---|---|
| Developer | Novo Nordisk | Eli Lilly | Eli Lilly |
| Brand Names | Ozempic, Wegovy, Rybelsus | Mounjaro, Zepbound | N/A (investigational) |
| Mechanism | GLP-1 only (single) | GLP-1 + GIP (dual) | GLP-1 + GIP + Glucagon (triple) |
| Molecular Weight | ~4,114 Da | ~4,810 Da | ~4,605 Da |
| FDA Approved | Yes | Yes | No |
| Max Weight Loss (trials) | ~15-17% | ~20-22.5% | ~26-29% (Phase 3) |
| Compounding Available | Restricted (see below) | No | No |
| Research Vendor Available | Yes | Yes | Limited |
Semaglutide — The Market Leader
Semaglutide is the most commercially successful peptide in history. It's the only GLP-1 available in three FDA-approved forms: Ozempic (T2D, injectable), Wegovy (weight management, injectable), and Rybelsus (T2D, oral tablet).
Brand Pricing & Savings
| Product | Indication | List Price | With Savings Programs |
|---|---|---|---|
| Ozempic | Type 2 diabetes | $800-1,200/month | Insurance often covers |
| Wegovy | Weight management | $1,300-1,600/month | As low as $149/month (eligible patients, through Aug 2026) |
| Rybelsus | Type 2 diabetes (oral) | $800-1,000/month | Insurance may cover |
Coming soon: Novo Nordisk announced list price cuts of ~35-50% effective January 1, 2027, bringing all three to approximately $675/month.
Compounded Semaglutide — What Changed
The FDA removed semaglutide from the drug shortage list on February 21, 2025. This mirrors what happened with tirzepatide and has significantly changed the compounding landscape:
- 503B outsourcing facilities can no longer produce compounded semaglutide under the broad shortage exemption
- 503A pharmacies continue patient-specific compounding under a narrower legal framework — but this is actively being litigated
- Availability is not guaranteed — some pharmacies have stopped, others continue under legal risk
- Typical cost: $129-299/month when available
The semaglutide compounding situation is evolving rapidly. Check with your pharmacy directly for current availability. What happened with tirzepatide compounding (full shutdown within months of shortage removal) is the template for how this could play out.
Tirzepatide — The Dual Agonist
Tirzepatide targets two receptors (GLP-1 + GIP), which is why clinical trials showed greater weight loss than semaglutide. Approved as Mounjaro (T2D, May 2022) and Zepbound (weight management, November 2023). Zepbound also received a second approval in December 2024 for moderate-to-severe obstructive sleep apnea in adults with obesity.
Compounding Is No Longer Legal
The FDA declared the tirzepatide shortage resolved (initially October 2024, re-confirmed December 2024). Enforcement discretion ended for 503A pharmacies in February 2025 and for 503B facilities in March 2025. A federal court upheld the decision in May 2025.
Some compounders offer "modified" tirzepatide with added ingredients (B12, different salt forms), but this exists in a regulatory gray area with emerging safety concerns — a 2026 medRxiv preprint identified a previously unknown impurity in tirzepatide/B12 combination products.
The only fully legal option for tirzepatide is brand Mounjaro or Zepbound ($800-1,200/month, with manufacturer savings programs available).
Retatrutide — The Triple Agonist (Investigational)
Retatrutide is the newest and most potent of the three, targeting GLP-1, GIP, and glucagon receptors simultaneously. The glucagon component actively increases energy expenditure and promotes fat oxidation — adding a calorie-burning element the others lack.
Trial Results
- Phase 2 (NEJM): 24.2% weight loss at 48 weeks
- Phase 3 TRIUMPH-4 (Dec 2025): 26.4% at 9mg, 28.7% at 12mg over 68 weeks
- Dose-dependent response confirmed across both phases
Availability
- Not FDA-approved — no pharmacy compounding is possible
- No legitimate pharmaceutical-grade product exists on the market
- Some research vendors offer it, but quality and authenticity vary significantly
- An NDA filing from Eli Lilly is anticipated but unconfirmed as of early 2026
Retatrutide is a complex and expensive molecule to synthesize. If a research vendor's price seems too low, it almost certainly is. Quality synthesis of triple-agonist peptides costs significantly more than simpler peptides.
Complete Comparison
| Factor | Semaglutide | Tirzepatide | Retatrutide |
|---|---|---|---|
| FDA Approved | Yes (3 products) | Yes (2 products) | No |
| Compounding Legal | Restricted (503A continues under legal challenge) | No | No |
| Research Vendor | Available | Available | Limited |
| Oral Form | Yes (Rybelsus) | No | No |
| Administration | Weekly injection or daily oral | Weekly injection | Weekly injection (trials) |
| Brand Cost | $800-1,600/month | $800-1,200/month | N/A |
| Compounded Cost | $129-299/month (when available) | N/A | N/A |
| Research Cost | $40-100/vial | $50-120/vial | $80-150+/vial |
COA Requirements by Compound
Semaglutide
- HPLC purity — 98%+ required
- Mass spectrometry — confirm MW ~4,114 Da
- Sterility and endotoxin testing — critical for injectable forms
- For compounded: pharmacy must provide full COA with potency verification
Tirzepatide
- HPLC purity — 98%+ required
- Mass spectrometry — confirm MW ~4,810 Da
- Salt form identification — verify whether acetate or sodium form
- Endotoxin testing — standard for injectable research compounds
Retatrutide
- HPLC purity — 95%+ minimum, 98%+ preferred
- Mass spectrometry — confirm molecular identity
- Amino acid sequence verification — critical for complex triple-agonist molecules
- Endotoxin testing — standard for injectable forms
Red Flags Across All Three
- Any source selling GLP-1 peptides without a prescription for human use
- Weight loss claims or dosing instructions in marketing materials
- "Pharmaceutical grade" claims for retatrutide (no such product exists)
- Compounding pharmacies that cannot provide sterility testing and COA documentation
- Prices significantly below market rates — GLP-1 peptides are expensive to synthesize properly
- Tirzepatide/B12 combination products (emerging safety concerns)
Storage Guide
| Form | Temperature | Shelf Life |
|---|---|---|
| Brand pen (unused) | 2-8°C (refrigerate) | Per label |
| Brand pen (in use) | Room temperature OK | 56 days (Ozempic); per label (others) |
| Compounded vial | 2-8°C | Per pharmacy label (typically 30-90 days) |
| Research powder (any) | 2-8°C | Months |
Key Sourcing Tips
- Semaglutide: Compounded options from licensed 503A pharmacies may still be available but are no longer guaranteed — verify directly. Check Novo Nordisk savings programs for brand options.
- Tirzepatide: Brand Mounjaro/Zepbound is the only fully legal option. Be cautious of "modified" compounded products.
- Retatrutide: Research-only. Exercise extreme caution — no quality guarantees exist for gray market products. Verify COAs thoroughly.
- For all three: never use research-grade products for personal use — injectable compounds require pharmaceutical-grade sterility
- The compounding landscape is shifting rapidly — monitor the [FDA shortage database](https://www.accessdata.fda.gov/scripts/drugshortages/) for updates