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
Authors' conclusion
In 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.
Study context
- Population
- Adults with obesity or overweight and/or T2D; ALT/AST < 3 × ULN (weight management programme) or ≤ 5 × ULN (T2D programme)
- Participants
- 11,220 adults7 Phase 3 trials
- Comparison
- Orforglipron vs pooled comparator
- Orforglipronn = 6,920
- Pooled comparatorn = 4,300reference
- Outcome
- Hepatic safety: changes from baseline in hepatic analytes (continuous and categorical), drug-induced liver injury/Hy's Law screening, hepatic AEs
- Follow-up
- Up to 104 weeks
Methodological detailsplacebo- and active-controlled trials
- Placebo- and active-controlled trials
Pooled result
As reported in the abstract
Hepatic safety
- Orforglipron associated with mean reductions in ALT/AST
- Categorical ALT/AST elevations generally balanced between orforglipron and comparators
- Incidence of hepatic AEs balanced between orforglipron and pooled comparators
Further pooled results
Subgroups by baseline aminotransferases (normal vs elevated)
- Results consistent in participants with normal and elevated baseline aminotransferases
Safety
ALT or AST ≥ 3 × ULN and TBIL ≥ 2 × ULN
ALT or AST ≥ 3 × ULN and TBIL ≥ 2 × ULN
- Alternative etiologies accounted for all orforglipron cases; none met drug-induced liver injury/Hy's Law criteria
Original publication
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. Diabetes Obes Metab. Published 23 June 2026. doi:10.
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