Results from a PHASE1 study (NCT06440980) investigating Orforglipron (LY3502970) in healthy participants who are Obese or Overweight were posted on 2026-07-17. The trial, which enrolled 533 participants, compared the pharmacokinetics of capsule and tablet formulations, showing generally comparable steady-state exposure across different doses. For instance, the 1 mg capsule had a geometric mean AUC of 80.2 ng*h/ml, while the 0.8 mg tablet had 78.9 ng*h/ml.
Background
Orforglipron (LY3502970) was investigated in healthy participants who are Obese or Overweight to compare the pharmacokinetic profiles and safety of its capsule and tablet formulations.
Trial design
The study, identified as NCT06440980, was a PHASE1 trial that enrolled 533 participants who were healthy and either Obese or Overweight. The main purpose was to assess how much orforglipron gets into the bloodstream and how long it takes the body to get rid of it when given as capsules compared to tablets. The safety and tolerability of both formulations were also evaluated. The study was conducted in two parts, with Part B specifically comparing different doses of orforglipron capsules and tablets.
Key results
Key pharmacokinetic results from Part B, specifically the steady-state Area Under the Concentration Time Curve from time zero to the end of the dosing interval (AUC[0-tau]) on Day 7, were reported for various doses and formulations:
For the 1 mg dose comparison:
- 1 mg LY3502970 Capsule QD (First Treatment): geometric mean AUC of 80.2 ng*h/ml (Geometric Coefficient of Variation 37.8)
- 1 mg LY3502970 Capsule QD (Second Treatment): geometric mean AUC of 82.1 ng*h/ml (Geometric Coefficient of Variation 39.7)
- 0.8 mg LY3502970 Tablet QD: geometric mean AUC of 78.9 ng*h/ml (Geometric Coefficient of Variation 36.6)
For the 3 mg dose comparison:
- 3 mg LY3502970 Capsule QD (First Treatment): geometric mean AUC of 240 ng*h/ml (Geometric Coefficient of Variation 38.8)
- 3 mg LY3502970 Capsule QD (Second Treatment): geometric mean AUC of 252 ng*h/ml (Geometric Coefficient of Variation 39.1)
- 2.5 mg LY3502970 Tablet QD: geometric mean AUC of 247 ng*h/ml (Geometric Coefficient of Variation 37.3)
For the 6 mg dose comparison:
- 6 mg LY3502970 Capsule QD (First Treatment): geometric mean AUC of 517 ng*h/ml (Geometric Coefficient of Variation 47.4)
- 6 mg LY3502970 Capsule QD (Second Treatment): geometric mean AUC of 541 ng*h/ml (Geometric Coefficient of Variation 60.4)
- 5.5 mg LY3502970 Tablet QD: geometric mean AUC of 524 ng*h/ml (Geometric Coefficient of Variation 45.4)
For the 12 mg dose comparison:
- 12 mg LY3502970 Capsule QD (First Treatment): geometric mean AUC of 829 ng*h/ml (Geometric Coefficient of Variation 46.4)
- 12 mg LY3502970 Capsule QD (Second Treatment): geometric mean AUC of 841 ng*h/ml (Geometric Coefficient of Variation 46.3)
- 9 mg LY3502970 Tablet QD: geometric mean AUC of 790 ng*h/ml (Geometric Coefficient of Variation 40.3)
What this means
The pharmacokinetic results from this PHASE1 study indicate that Orforglipron, when administered as either a capsule or a tablet, achieves generally comparable steady-state systemic exposure across different dose levels. This similarity in AUC values between the two formulations, despite slight differences in nominal doses for the tablets, suggests that both oral dosage forms could provide similar drug delivery. This finding is important for the potential flexibility in formulation and administration of Orforglipron for future clinical development.
Source
This information was sourced from ClinicalTrials.gov, documenting the results of trial NCT06440980, which were posted on 2026-07-17. The study details are available on clinicaltrials.gov.