FGF21 analogs (efruxifermin / pegozafermin / efimosfermin)
Metabolic Health · FGF21 analog / MASH pipeline
Tier C+
Bottom line
Read Off Label grades FGF21 analogs (efruxifermin / pegozafermin / efimosfermin) as C+ (5.7/10) based on moderate evidence, med-high benefit magnitude, and a med-risk safety profile.
Promoted from watchlist because the class now has several named, active Phase 3 MASH programs plus peer-reviewed Phase 2b human data.
Studied, labeled, or reported-use context: Weekly or every-2-week SC injection in trials: efruxifermin 28-50 mg weekly; pegozafermin 15-30 mg… — Investigational; not individualized guidance.
What the evidence says
Promoted from watchlist because the class now has several named, active Phase 3 MASH programs plus peer-reviewed Phase 2b human data. Efruxifermin HARMONY 96-week results showed sustained histologic MASH/fibrosis signal; pegozafermin ENLIVEN showed NASH/MASH improvements and large triglyceride/liver-fat effects; efimosfermin alfa has Phase 2a data and Phase 3 trials recruiting. Still an investigational liver-disease class, not a general longevity drug. Industry-funded trials; clinical outcomes and long-term safety pending. Novo Nordisk acquired Akero Therapeutics (efruxifermin) in Oct 2025 (~$5.2B); efruxifermin Phase 2b SYMMETRY showed compensated-cirrhosis reversal (39% vs 15% placebo at 50 mg). Pegozafermin Phase 3 ENLIGHTEN-Fibrosis topline expected H1 2027 and ENLIGHTEN-Cirrhosis in 2028. A 2026 systematic review/meta-analysis of 10 RCTs (n=1,113, F1-F4 fibrosis) confirmed FGF21 analogues significantly improve >=1-stage liver fibrosis vs placebo (Int J Hepatol 2026).
Mechanism
Long-acting fibroblast growth factor 21 analogs activate FGFR1c/β-Klotho signaling to improve hepatic fat metabolism, insulin sensitivity, triglycerides, adiponectin, and liver inflammation/fibrosis biology.
Studied, labeled, or reported dose & route
Weekly or every-2-week SC injection in trials: efruxifermin 28-50 mg weekly; pegozafermin 15-30 mg weekly or 44 mg Q2W; efimosfermin alfa trial dosing varies
This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.
Citations
- PubMed · PMID 40818852
- PubMed · PMID 37356033
- PubMed · PMID 40484014
- ClinicalTrials.gov · NCT06318169
- ClinicalTrials.gov · NCT07221227
A link means the source informed this entry; it does not mean every claim on the page comes from that source. If a citation looks wrong or you want a claim re-checked, send a correction.
Common questions
- What does the evidence show about FGF21 analogs (efruxifermin / pegozafermin / efimosfermin)'s effects?
- Read Off Label rates the evidence for FGF21 analogs (efruxifermin / pegozafermin / efimosfermin) as Moderate and the benefit magnitude as med-high, producing an overall grade of C+ (5.7/10). Promoted from watchlist because the class now has several named, active Phase 3 MASH programs plus peer-reviewed Phase 2b human data.
- What safety findings are reported for FGF21 analogs (efruxifermin / pegozafermin / efimosfermin)?
- FGF21 analogs (efruxifermin / pegozafermin / efimosfermin) has a med risk profile in the database. Med (GI effects, injection-site reactions, appetite/weight effects; long-term bone and class safety still being defined) Legal status: Investigational (Phase 3 MASH programs; no FDA-approved product).
- What doses or routes are reported for FGF21 analogs (efruxifermin / pegozafermin / efimosfermin)?
- Weekly or every-2-week SC injection in trials: efruxifermin 28-50 mg weekly; pegozafermin 15-30 mg weekly or 44 mg Q2W; efimosfermin alfa trial dosing varies This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
- How does FGF21 analogs (efruxifermin / pegozafermin / efimosfermin) work?
- Long-acting fibroblast growth factor 21 analogs activate FGFR1c/β-Klotho signaling to improve hepatic fat metabolism, insulin sensitivity, triglycerides, adiponectin, and liver inflammation/fibrosis biology.
This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.