Pegozafermin Side Effects: What Studies Report

This page summarises what peer-reviewed publications stated about adverse events and tolerability observed in studies of pegozafermin. It reports findings only; it does not interpret them for any individual situation. This page is for educational purposes only and is not medical advice; consult a licensed physician about any medical decision or symptom.

What pegozafermin is in the published literature

Pegozafermin is a glycoPEGylated analogue of fibroblast growth factor 21 (FGF21). It was administered as a subcutaneous injection in a randomised, double-blind, placebo-controlled phase 2b trial in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH) and stage F2–F3 fibrosis, in which participants received 15 mg weekly, 30 mg weekly or 44 mg once every two weeks for 24 weeks (PMID 37356033). Before that trial, a randomised, double-blind, placebo-controlled phase 1b/2a multiple-ascending-dose study examined the safety, pharmacokinetics and pharmacodynamics of pegozafermin in patients with non-alcoholic steatohepatitis (PMID 36521501). A separate randomised phase 2 trial evaluated the FGF21 analogue in adults with severe hypertriglyceridaemia (PMID 37355760).

Additional publications described the same programme from other angles: a clinical trial report examined effects of pegozafermin on the liver and on metabolic comorbidities in subjects with biopsy-confirmed nonalcoholic steatohepatitis (PMID 37718721), and a population pharmacokinetics and pharmacodynamics analysis modelled exposure and response in patients with nonalcoholic steatohepatitis (PMID 37696614). Because the compound has been studied in these defined trial populations, the adverse-event picture summarised below reflects those settings and those durations, not general or long-term use.

Gastrointestinal Adverse Events: What Studies Report

The most consistently described tolerability finding came from the phase 2b NASH trial, where researchers reported that nausea and diarrhoea were the most frequent adverse events among patients who received pegozafermin and characterised these events as mostly mild or moderate in severity (PMID 37356033). That trial's safety reporting covered a 24-week randomised, placebo-controlled period in participants with biopsy-confirmed NASH and stage F2–F3 fibrosis (PMID 37356033).

At the class level, a systematic review and meta-analysis of fibroblast growth factor-21 analogues for metabolic dysfunction-associated steatohepatitis pooled randomised evidence on both efficacy and safety, and adverse-event frequency was one of the outcomes the authors assessed across those trials (PMID 38666606). Pooled analyses of this kind combine agents that differ in structure and dosing schedule, so the meta-analysis described the FGF21 analogue class rather than pegozafermin alone (PMID 38666606).

Early-Phase Safety Findings: What Studies Report

The phase 1b/2a multiple-ascending-dose study was explicitly designed around safety as well as pharmacokinetics and pharmacodynamics, meaning that dose escalation and tolerability observations were primary features of the study rather than secondary ones (PMID 36521501). In a related clinical trial report, investigators described effects of pegozafermin on hepatic measures and on metabolic comorbidities in subjects with biopsy-confirmed nonalcoholic steatohepatitis (PMID 37718721).

Population modelling added a different kind of safety-relevant information. The population pharmacokinetics and pharmacodynamics analysis characterised how drug exposure related to measured responses in patients with nonalcoholic steatohepatitis, which is the type of analysis used to understand whether higher exposure tracks with larger biological effects (PMID 37696614). Exposure–response modelling of this sort describes pharmacology; it does not by itself establish an adverse-event profile (PMID 37696614).

Why early-phase tolerability data are limited by design

Multiple-ascending-dose studies enrol relatively small numbers of participants for relatively short periods, and the phase 1b/2a pegozafermin study followed that structure in patients with non-alcoholic steatohepatitis (PMID 36521501). Rare events, delayed events and events requiring long follow-up are generally not detectable at that scale, and the papers cited on this page did not report outcomes beyond the durations each trial specified, such as the 24-week randomised period of the phase 2b NASH trial (PMID 37356033).

Safety in Severe Hypertriglyceridaemia Studies: What Studies Report

A randomised phase 2 trial examined the FGF21 analogue pegozafermin in severe hypertriglyceridaemia and reported both lipid outcomes and safety observations in that population (PMID 37355760). A review of recent clinical trials for the prevention of acute pancreatitis in chylomicronaemia syndromes placed pegozafermin among the agents evaluated for severe triglyceride elevation and discussed what those trials did and did not establish about clinical event prevention (PMID 41208140).

Broader pharmacology reviews covered the same territory. A review of current and emerging pharmacological therapies for hypertriglyceridaemia described the range of mechanisms under study, including FGF21 analogues (PMID 42074213), and a review of pemafibrate and other triglyceride-lowering therapies discussed the relationship between triglyceride lowering and cardiovascular or metabolic risk (PMID 38482842). A further review of triglyceride-lowering therapies for hepatic steatosis addressed mechanisms, efficacy and clinical perspectives across this therapeutic area (PMID 42206171).

Mechanistic context researchers gave for FGF21 analogues

Interpretation of adverse events in this class is shaped by FGF21 biology. A review of the role of FGF21 in heart failure discussed molecular insights and therapeutic implications of FGF21 signalling, illustrating that the pathway is studied well beyond the liver (PMID 41198096). A review of NAFLD in the 21st century summarised current knowledge of pathogenesis, diagnosis and therapeutics, the framework within which steatohepatitis drug candidates including FGF21 analogues have been evaluated (PMID 38672181).

Reviews of this type explain plausible mechanisms; they are not sources of adverse-event incidence. The quantitative tolerability information in the literature cited here came from the randomised trials and from the pooled analysis of FGF21 analogues in metabolic dysfunction-associated steatohepatitis (PMID 38666606).

Study-by-study overview

Gaps in the cited safety literature

Several questions commonly asked about an investigational injectable were not answered by the publications listed here, and that absence is worth stating plainly rather than filling in.

• Duration. The longest randomised exposure described among the cited papers was the 24-week period of the phase 2b NASH trial, so outcomes over years were not established by that study (PMID 37356033).
• Populations outside the trials. The randomised studies cited here enrolled patients with non-alcoholic steatohepatitis (PMID 36521501) or severe hypertriglyceridaemia (PMID 37355760); healthy-population, paediatric and pregnancy data were not among these reports.
• Hard clinical endpoints. A review of recent trials for the prevention of acute pancreatitis in chylomicronaemia syndromes discussed how far trial evidence has progressed toward event prevention in that setting (PMID 41208140).
• Class versus compound. Where safety was pooled, the analysis addressed FGF21 analogues collectively rather than a single agent (PMID 38666606).

Reading these safety reports in context

Adverse events recorded in a randomised trial are counts within a defined protocol, comparison group and follow-up window. In the phase 2b NASH trial, the comparison was against placebo over 24 weeks in a biopsy-defined population (PMID 37356033), while the phase 1b/2a study assessed safety across escalating dose levels in a smaller sample (PMID 36521501). Reviews summarising the wider field, including work on triglyceride-lowering therapies for hepatic steatosis (PMID 42206171) and on emerging therapies for hypertriglyceridaemia (PMID 42074213), set that evidence alongside other mechanisms under investigation.

Readers looking for the underlying pharmacology, trial design history and endpoint definitions will find those topics covered separately in the pegozafermin course; this page is limited to what published studies reported about adverse events and tolerability. Again, this page is educational only and is not medical advice; questions about symptoms, monitoring or any therapy belong with a licensed physician.

References

• Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH (The New England Journal of Medicine, 2023)
• Safety, pharmacokinetics, and pharmacodynamics of pegozafermin in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study (The Lancet Gastroenterology & Hepatology, 2023)
• The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial (Nature Medicine, 2023)
• Clinical trial: Effects of pegozafermin on the liver and on metabolic comorbidities in subjects with biopsy-confirmed nonalcoholic steatohepatitis (Alimentary Pharmacology & Therapeutics, 2023)
• Efficacy and Safety of Fibroblast Growth Factor-21 Analogs for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis (Clinical Pharmacology and Therapeutics, 2024)
• Population Pharmacokinetics and Pharmacodynamics of Pegozafermin in Patients with Nonalcoholic Steatohepatitis (Clinical Pharmacology and Therapeutics, 2023)
• Lessons from recent clinical trials for the prevention of acute pancreatitis in chylomicronemia syndromes (Current Opinion in Endocrinology, Diabetes, and Obesity, 2026)
• Role of FGF21 in Heart Failure: Molecular Insights and Therapeutic Implications (Cardiology in Review, 2025)
• Current and Emerging Pharmacological Therapies for Hypertriglyceridemia (International Journal of Molecular Sciences, 2026)
• Triglyceride-lowering therapies for hepatic steatosis: mechanisms, efficacy, and clinical perspectives (Frontiers in Pharmacology, 2026)
• Pemafibrate and other triglyceride-lowering therapies to reduce risk of cardiovascular and metabolic disease (Current Opinion in Cardiology, 2024)
• NAFLD in the 21st Century: Current Knowledge Regarding Its Pathogenesis, Diagnosis and Therapeutics (Biomedicines, 2024)