Case Report: Semaglutide Linked to Liver Injury, Confirmed by Rechallenge

A 44-year-old woman developed liver injury after starting semaglutide for weight management, with enzyme levels normalizing after discontinuation and worsening upon rechallenge, confirming the drug as the cause.

Kalsi, Harsimran et al.·ACG case reports journal·2025·
RPEP-116842025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Not classified
Evidence
Not graded
Sample
Not reported

What This Study Found

A 44-year-old woman developed drug-induced liver injury (DILI) after semaglutide initiation for weight management. The causal relationship was confirmed by a positive dechallenge-rechallenge pattern: liver enzymes normalized after discontinuation and elevated again when semaglutide was restarted.

The authors conducted a literature review of all reported semaglutide-related DILI cases, finding that hepatotoxicity from semaglutide, while exceedingly rare, is a documented adverse effect that warrants clinical awareness.

Key Numbers

How They Did This

Single patient case report with literature review. The case involved clinical documentation of liver enzyme changes correlated with semaglutide initiation, discontinuation, and rechallenge. The accompanying literature review surveyed all previously published cases of semaglutide-induced liver injury.

Why This Research Matters

Semaglutide (Ozempic/Wegovy) is one of the most widely prescribed medications in the world, with millions of users for diabetes and weight management. While liver injury is rare, the enormous and rapidly growing user base means even uncommon side effects can affect many people. This case reinforces the importance of liver monitoring and raises awareness among prescribers.

The Bigger Picture

As GLP-1 receptor agonists become among the most prescribed drugs globally, post-marketing surveillance for rare adverse effects is critical. Most clinical trials are not large enough or long enough to detect very uncommon side effects. Case reports like this, while limited in scale, serve as early warning signals that help build the safety profile of these medications over time.

What This Study Doesn't Tell Us

This is a single case report, the lowest level of clinical evidence. Individual case reports cannot establish incidence rates or risk factors. Other potential causes of liver injury may not have been completely excluded despite the positive rechallenge. The literature review scope and methodology are not detailed in the abstract.

Questions This Raises

  • ?What is the estimated incidence of semaglutide-induced liver injury across the millions of users worldwide?
  • ?Are there specific patient risk factors — such as pre-existing liver conditions or concurrent medications — that increase susceptibility?
  • ?Is the hepatotoxicity specific to semaglutide or could it occur with other GLP-1 receptor agonists?

Trust & Context

Key Stat:
Positive rechallenge Liver injury resolved when semaglutide was stopped and returned when restarted — the strongest evidence of causation in a case report
Evidence Grade:
This is a single case report with literature review — the lowest tier of clinical evidence, but the positive dechallenge-rechallenge pattern provides strong evidence of causation in this individual patient.
Study Age:
Published in 2025, this report is very timely given the explosive growth in semaglutide prescriptions for both diabetes and weight management.
Original Title:
Semaglutide-Induced Liver Injury.
Published In:
ACG case reports journal, 12(8), e01776 (2025)
Database ID:
RPEP-11684

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

Should people on semaglutide be worried about liver damage?

Liver injury from semaglutide is described as exceedingly rare. Most patients take the medication without liver problems. However, this case highlights the importance of being aware of symptoms like unusual fatigue, yellowing of skin or eyes, dark urine, or upper abdominal pain, and reporting them to a doctor promptly.

What does 'positive rechallenge' mean and why is it significant?

A positive rechallenge means the patient's liver injury went away when semaglutide was stopped, then came back when the drug was restarted. This is considered the strongest form of evidence in a case report that a specific drug caused the adverse effect, because it rules out coincidence.

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Cite This Study

RPEP-11684·https://rethinkpeptides.com/research/RPEP-11684

APA

Kalsi, Harsimran; Arora, Samneet Singh; Essilfie-Quaye, Kobina; Bassi, Raghav; Akhavan, Neeka; Perbtani, Yaseen; Brar, Tony S. (2025). Semaglutide-Induced Liver Injury.. ACG case reports journal, 12(8), e01776. https://doi.org/10.14309/crj.0000000000001776

MLA

Kalsi, Harsimran, et al. "Semaglutide-Induced Liver Injury.." ACG case reports journal, 2025. https://doi.org/10.14309/crj.0000000000001776

RethinkPeptides

RethinkPeptides Research Database. "Semaglutide-Induced Liver Injury." RPEP-11684. Retrieved from https://rethinkpeptides.com/research/kalsi-2025-semaglutideinduced-liver-injury

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.