B7-33 vs Glepaglutide
Comprehensive side-by-side comparison of mechanisms, dosing, side effects, and research
Also: B7-33 relaxin, Single-chain relaxin-2 analog
B7-33 is a 27-amino-acid, single-chain peptide cut down from the B-chain of human relaxin-2, the hormone that loosens tissue during pregnancy. Relaxin itself has strong anti-scarring effects but is a complex two-chain molecule that is hard and expensive to make, so an Australian group (Hossain and colleagues, 2016) designed B7-33 as a simpler version. In rodent models it reduced heart and lung fibrosis about as well as full relaxin. It has never been tested in humans.
Also: ZP1848, Zeydovio
Glepaglutide is Zealand Pharma's long-acting GLP-2 analog for short bowel syndrome, built to be injected once or twice a week instead of daily like teduglutide. Its path has been bumpy. The FDA rejected it in December 2024 because the single phase 3 trial only worked at the twice-weekly dose, but Europe went the other way: in September 2026 the EMA's CHMP recommended approval under the name Zeydovio. As of late October 2026 the final European Commission decision is still pending, and the US needs another trial.
Key Comparison Insights
- Both peptides belong to the Healing category, suggesting similar primary applications.
- Glepaglutide has stronger research evidence (Human Trials) compared to B7-33 (Preclinical).
Detailed Comparison
| Attribute | B7-33 | Glepaglutide |
|---|---|---|
| Category | Healing | Healing |
| FDA Status | Not FDA Approved | Not FDA Approved |
| Clinical Status | Pre I II III IV FDA | Pre I II III IV FDA |
| Mechanism of Action | B7-33 activates RXFP1, the relaxin receptor, but in an unusual way. In cells that naturally carry RXFP1 (like fibroblasts), it preferentially switches on the pERK1/2 pathway rather than the cAMP pathway, which made it the first described functionally selective (biased) RXFP1 agonist. Its anti-fibrotic action runs through RXFP1 paired with the angiotensin II type 2 receptor, increasing MMP-2, an enzyme that breaks down collagen. In other words, it pushes scar tissue to be broken down rather than built up. Two practical caveats: it binds RXFP1 poorly in standard engineered cell lines, so its potency depends heavily on the cell type, and it is short-lived in serum (roughly 6 minutes in lab tests), which is why researchers have tried fatty-acid versions to stretch its half-life. | Glepaglutide activates the GLP-2 receptor in the intestine, the same target as teduglutide, which makes the gut lining grow and absorb more fluid and nutrients. What is different is the delivery. After a subcutaneous injection it forms a depot and is slowly released, mostly as two active metabolites rather than the parent molecule. In a healthy-volunteer study the effective half-life was roughly 88 to 124 hours, long enough to make weekly or twice-weekly dosing plausible. The flip side is the same as the rest of the GLP-2 class: anything that makes gut tissue grow raises questions about polyps and tumors over the long run. |
| Common Dosing | No established human dose Once to twice daily in mouse studies | 10 mg twice weekly (trial dose) Twice weekly |
| Administration | Intraperitoneal or subcutaneous injection (including osmotic minipumps) in rodents | Subcutaneous injection (prefilled pen in the EU filing) |
| Typical Duration | 1-2 weeks in most rodent studies | 24 weeks in EASE-1, with longer-term extension studies |
| Best Time to Take | No evidence-based timing | Same days each week (trial schedule) |
Possible Side Effects May vary by individual |
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| Research Summary | The founding paper (Hossain et al., Chemical Science, 2016) reported that B7-33 prevented or reversed organ fibrosis and dysfunction in three rodent models of heart or lung disease with potency similar to full relaxin-2, and, unlike native relaxin, it did not promote prostate tumor growth in mice. That last point matters because relaxin has been linked to tumor growth. Later mouse work extended the findings: Devarakonda et al. (Journal of the American Heart Association, 2020) gave 0.25 mg/kg twice daily by injection after a heart attack and found smaller infarcts, better heart function, and less fibrosis at 7 days. A 2023 follow-up from the original group confirmed that B7-33 cannot be shortened further without losing receptor binding. Important context: the full hormone (serelaxin) went all the way to a large phase 3 trial in acute heart failure (RELAX-AHF-2) and failed both primary endpoints, a reminder that strong animal anti-fibrotic data in this family have not translated easily to people. For B7-33 itself there are no human studies, no human pharmacokinetics, and no human safety data. | The main evidence is EASE-1, published in Gastroenterology in April 2025 (Jeppesen and colleagues). It randomized 106 adults with SBS and intestinal failure to glepaglutide 10 mg twice weekly, 10 mg once weekly, or placebo for 24 weeks. Twice weekly cut weekly parenteral support by 5.13 L versus 2.85 L on placebo (p=0.0039), and 65.7% were responders versus 38.9% on placebo. Once weekly (3.13 L) did not reach significance. A handful of patients came off IV support completely, none on placebo. On 19 December 2024 the FDA issued a complete response letter saying there was not enough evidence at the to-be-marketed dose and asked for another trial; Zealand is running EASE-5 to support a US resubmission. Zealand filed in Europe in June 2025 and the CHMP gave a positive opinion on 17 September 2026 for adults with SBS (10 mg prefilled pen). Common side effects listed by the EMA are injection site reactions, abdominal pain, nausea, and vomiting. Bottom line: real phase 3 data, but from a single trial with one of two doses positive, which is exactly why the two regulators disagreed. |
Frequently Asked Questions: B7-33 vs Glepaglutide
What is the difference between B7-33 and Glepaglutide?
B7-33 is a healing peptide that b7-33 is a 27-amino-acid, single-chain peptide cut down from the b-chain of human relaxin-2, the hormone that loosens tissue during pregnancy. relaxin itself has strong anti-scarring effects but is a complex two-chain molecule that is hard and expensive to make, so an australian group (hossain and colleagues, 2016) designed b7-33 as a simpler version. in rodent models it reduced heart and lung fibrosis about as well as full relaxin. it has never been tested in humans. Glepaglutide is a healing peptide that glepaglutide is zealand pharma's long-acting glp-2 analog for short bowel syndrome, built to be injected once or twice a week instead of daily like teduglutide. its path has been bumpy. the fda rejected it in december 2024 because the single phase 3 trial only worked at the twice-weekly dose, but europe went the other way: in september 2026 the ema's chmp recommended approval under the name zeydovio. as of late october 2026 the final european commission decision is still pending, and the us needs another trial. The main differences lie in their mechanisms of action and clinical applications.
Which is better, B7-33 or Glepaglutide?
Neither is universally "better" - the choice depends on your specific goals. B7-33 is typically used for healing purposes, while Glepaglutide is used for healing. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can B7-33 and Glepaglutide be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using B7-33 and Glepaglutide together should only be considered under medical supervision, as both compounds have their own side effect profiles and potential interactions. Research on their combined use may be limited.