Trial results for a Phase 1 study of Orforglipron (LY3502970) evaluating pharmacokinetics in participants with normal and impaired renal function were posted on ClinicalTrials.gov on 2026-06-09. The study found that the geometric mean Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC0-∞) was 167 nanogram*hour per milliliter (ng*hr/mL) in severe renal impairment, compared to 113 ng*hr/mL in normal renal function.
Background
This Phase 1 study aimed to assess the pharmacokinetics of LY3502970, specifically its absorption and elimination, in participants with varying degrees of renal impairment compared to those with normal renal function. Safety and tolerability were also evaluated.
Trial design
The completed Phase 1, parallel, single-dose, open-label study (NCT05936138) enrolled 24 participants with either normal renal function or renal impairment. The primary objective was to characterize the pharmacokinetics of LY3502970, including area under the concentration-time curve and maximum observed concentration, across these groups. Safety and tolerability were secondary assessments.
Key results
The study reported detailed pharmacokinetic measurements for LY3502970:
- Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-∞):
- Normal Renal Function: 113 ng*hr/mL (Geometric CV: 32.1%)
- Severe Renal Impairment: 167 ng*hr/mL (Geometric CV: 48.6%)
- End-Stage Renal Disease: 108 ng*hr/mL (Geometric CV: 87.8%)
- Area Under the Concentration Versus Time Curve From Time Zero to Last Time Point (AUC0-tlast):
- Normal Renal Function: 98.9 ng*hr/mL (Geometric CV: 32.9%)
- Severe Renal Impairment: 120 ng*hr/mL (Geometric CV: 48.9%)
- End-Stage Renal Disease: 90.2 ng*hr/mL (Geometric CV: 79.7%)
- Maximum Observed Concentration (Cmax):
- Normal Renal Function: 5.01 ng/mL (Geometric CV: 20.7%)
- Severe Renal Impairment: 6.01 ng/mL (Geometric CV: 54.9%)
- End-Stage Renal Disease: 4.29 ng/mL (Geometric CV: 67.3%)
What this means
The pharmacokinetic results indicate that exposure to Orforglipron, as measured by AUC0-∞ and Cmax, is generally higher in participants with severe renal impairment compared to those with normal renal function. For instance, the geometric mean AUC0-∞ was 167 ng*hr/mL in severe renal impairment versus 113 ng*hr/mL in normal renal function. Conversely, participants with end-stage renal disease showed an AUC0-∞ of 108 ng*hr/mL, which was comparable to or slightly lower than that in normal renal function. These findings suggest that renal function significantly influences the pharmacokinetics of Orforglipron, which may necessitate dose adjustments or careful monitoring in patients with varying degrees of renal impairment.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT05936138 were posted on 2026-06-09 on clinicaltrials.gov.