Evidence mapPaperPMID 42338042Full record

Trial reportDiabetes, obesity & metabolism2026

Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and/or Type 2 Diabetes: A Pooled Analysis of the Orforglipron Phase 3 Clinical Trials.

Sean Wharton, Adam Stefanski, Jiaxun Chen, Girish Rao, Elvis Asare Twum, Max Denning

Abstract readClinical Trial, Phase III
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Sean WhartonUniversity of Toronto, and Wharton Weight Management Clinic, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0003-0111-1530
Adam StefanskiEli Lilly and Company, Indianapolis, Indiana, USA.ORCID https://orcid.org/0009-0001-7598-402X
Jiaxun ChenEli Lilly and Company, Indianapolis, Indiana, USA.ORCID https://orcid.org/0000-0002-7046-4201
Girish RaoEli Lilly and Company, Indianapolis, Indiana, USA.ORCID https://orcid.org/0000-0002-3660-5488
Elvis Asare TwumEli Lilly and Company, Indianapolis, Indiana, USA.ORCID https://orcid.org/0009-0006-1093-2508
Max DenningEli Lilly and Company, Indianapolis, Indiana, USA.ORCID https://orcid.org/0000-0001-6215-6885

Funding

Eli Lilly and Company
6 · The paper itself

Abstract

aimsOrforglipron is a novel small-molecule, once daily oral non-peptide GLP-1 receptor agonist. The hepatic safety profile in adults with obesity or overweight and/or type 2 diabetes (T2D) across seven orforglipron Phase 3 clinical trials was assessed. MATERIALS AND

methodsOverall, 11 220 participants were included in this analysis (orforglipron N = 6920; pooled comparator [placebo, oral semaglutide, dapagliflozin, insulin glargine] N = 4300) for up to 104 weeks, including safety follow-up. Eligibility criteria for these Phase 3 trials included ALT/AST < 3 × ULN in the weight management programme and ≤ 5 × ULN in the T2D programme. The main analysis sets included placebo-controlled trials by indication for pooled orforglipron doses. Changes from baseline in hepatic analytes were assessed continuously and categorically, and screening for drug-induced liver injury/Hy's Law was conducted. Hepatic AEs were summarised. Subgroup analyses were conducted in participants with elevated baseline aminotransferases.

resultsOrforglipron treatment was associated with mean reductions in ALT/AST. Categorical ALT/AST elevations were generally balanced between orforglipron and comparators. Six (0.1%) orforglipron-treated participants and six (0.1%) comparator-treated participants had ALT or AST ≥ 3 × ULN and TBIL ≥ 2 × ULN; however, alternative etiologies accounted for all orforglipron cases and thus did not meet criteria for drug induced liver injury/Hy's Law. The incidence of hepatic AEs was balanced between orforglipron and pooled comparators, suggesting no increased risk with orforglipron. Results were consistent in participants with normal and elevated baseline aminotransferases.

conclusionsIn this pooled analysis of orforglipron Phase 3 clinical trials, orforglipron treatment was not associated with drug-induced liver injury, demonstrating a hepatic safety profile similar to placebo or active comparators. There were no cases consistent with drug-induced liver injury/Hy's Law with orforglipron. Aminotransferase trajectories showed a hepatic profile consistent with the metabolic benefits of weight loss.

Indexed as

Chemical and Drug Induced Liver InjuryDiabetes Mellitus, Type 2Hypoglycemic AgentsLiverObesityOverweightAdultAgedAlanine TransaminaseBenzhydryl CompoundsClinical Trials, Phase III as TopicFemaleFluorine CompoundsGlucagon-Like PeptidesGlucosidesHumansAlanine TransaminaseBenzhydryl CompoundsdapagliflozinFluorine CompoundsGlucagon-Like PeptidesGlucosidesHypoglycemic AgentsInsulin GlargineorforglipronOxadiazolesSemaglutideACHIEVEATTAINhepatic safetyobesityorforgliprontype 2 diabetes

Identifiers

PMID42338042
PMCPMC13448879

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.