Results from a Phase 1 study investigating the pharmacokinetics of Orforglipron (LY3502970) in participants with impaired and normal liver function were posted on ClinicalTrials.gov on 2026-05-27. The study found that the geometric mean Area Under the Concentration Versus Time Curve from time zero to infinity (AUC [0-∞]) of Orforglipron was 611 nanogram *hour per milliliter (ng*h/mL) in participants with severe hepatic impairment, compared to 130 ng*h/mL in those with normal hepatic function.
Background
This study aimed to measure the systemic exposure and elimination of LY3502970 in participants across different levels of hepatic function: mild, moderate, and severe impairment, as well as in a control group with normal liver function. The safety and tolerability of LY3502970 were also evaluated as part of the study's objectives.
Trial design
The completed Phase 1 study (NCT05882032) enrolled 29 participants, including those categorized as Healthy and those with varying degrees of Hepatic Insufficiency. The intervention involved administering 1 mg LY3502970. The main purpose of the study was to assess the pharmacokinetics of LY3502970, specifically how much of the drug entered the bloodstream and its elimination rate, across these different hepatic function groups.
Key results
The study reported key pharmacokinetic measurements for 1 mg LY3502970 across different hepatic function groups:
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of LY3502970
- Control (Normal Hepatic Function): Geometric mean of 130 ng*h/mL (Geometric Coefficient of Variation: 26.8%)
- Mild Hepatic Impairment: Geometric mean of 132 ng*h/mL (Geometric Coefficient of Variation: 60.2%)
- Moderate Hepatic Impairment: Geometric mean of 209 ng*h/mL (Geometric Coefficient of Variation: 32.6%)
- Severe Hepatic Impairment: Geometric mean of 611 ng*h/mL (Geometric Coefficient of Variation: 84.6%)
- PK: Area Under the Concentration Versus Time Curve From Time Zero to Last Time Point (AUC0-tlast) of LY3502970
- Control (Normal Hepatic Function): Geometric mean of 109 ng*h/mL (Geometric Coefficient of Variation: 29.1%)
- Mild Hepatic Impairment: Geometric mean of 112 ng*h/mL (Geometric Coefficient of Variation: 64.0%)
- Moderate Hepatic Impairment: Geometric mean of 169 ng*h/mL (Geometric Coefficient of Variation: 32.7%)
- Severe Hepatic Impairment: Geometric mean of 385 ng*h/mL (Geometric Coefficient of Variation: 54.7%)
- PK: Maximum Observed Concentration (Cmax) of LY3502970
- Control (Normal Hepatic Function): Geometric mean of 5.10 nanograms per milliliter (ng/mL) (Geometric Coefficient of Variation: 21.0%)
- Mild Hepatic Impairment: Geometric mean of 5.47 ng/mL (Geometric Coefficient of Variation: 57.5%)
- Moderate Hepatic Impairment: Geometric mean of 6.12 ng/mL (Geometric Coefficient of Variation: 43.6%)
- Severe Hepatic Impairment: Geometric mean of 5.95 ng/mL (Geometric Coefficient of Variation: 36.1%)
What this means
The pharmacokinetic results for Orforglipron indicate that systemic exposure, as measured by AUC [0-∞] and AUC0-tlast, increases with the severity of hepatic impairment. Specifically, participants with severe hepatic impairment experienced a substantially higher exposure to the drug compared to those with normal liver function. The Cmax values, however, showed less variability across the different hepatic function groups. These findings suggest that dose adjustments for Orforglipron may be necessary for patients with moderate to severe hepatic impairment to manage drug exposure and potential safety implications.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT05882032, titled "A Study of LY3502970 in Participants With Impaired and Normal Liver Function", were posted on 2026-05-27 on clinicaltrials.gov.