HealthyPhase 1NCT06186622

A Drug-Drug Interaction Study of Orforglipron (LY3502970) in Healthy Overweight and Obese Participants

A Phase 1 study testing Orforglipron, Simvastatin and Digoxin in people with Healthy and Obese, run by Eli Lilly and Company at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Healthy, Obese, Overweight
What is being tested?: Orforglipron, Simvastatin and Digoxin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 50 participants
Where: 2 sitesUnited States
Study dates: 2 Jan 2024to 10 Jul 2024
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Participants who are overtly healthy as determined by medical history and physical examination.
Have body mass index (BMI) equal to or greater than 27 kilograms per meter squared (kg/m²), inclusive, at screening.
Have an estimated glomerular filtration rate equal to or greater than 60 milliliters per minute (mL/min).
Males and females who agree to follow contraceptive requirements, or women not of childbearing potential (WNOCBP).
Have venous access sufficient to allow for blood sampling.

Who cannot join

Have any type of diabetes with hemoglobin A1c (HbA1c) level of 6.5 percent (%) or greater.
Have significant history of or currently have Major Depressive Disorder or psychiatric disorder within the last 2 years.
Obesity induced by other endocrine disorders, such as Cushing's syndrome or Prader-Willi syndrome.
Have known clinically significant gastric emptying abnormality.
Have undergone bariatric surgery (for example: Lap-Band, Gastric Bypass)
Have a known self or family history (first-degree relative) of multiple endocrine neoplasia type 2A or type 2B, thyroid C-cell hyperplasia, or any form of thyroid cancer.

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Have an abnormal 12-lead electrocardiogram (ECG) at screening.
Have significant previous or current history of comorbidities capable of significantly altering the absorption, metabolism, or elimination of drug.
Participants must not be currently participating in or completed a clinical trial within the last 90 days.
Have a known allergy or hypersensitivity to midazolam, simvastatin, rosuvastatin, or digoxin.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Fortrea Clinical Research Unit Inc.
Dallas, Texas, 75247
Fortrea Clinical Research Unit Inc.
Daytona Beach, Florida, 32117

Other trials in United States

About this study

Official title: A Drug-Drug Interaction Study to Assess the Effect of Orforglipron on the Pharmacokinetics of Digoxin, Simvastatin, Rosuvastatin, Acetaminophen, and Midazolam in Healthy Overweight and Obese Participants

The main purpose of this study is to determine effect of orforglipron capsule formulation on the amount of digoxin, rosuvastatin, acetaminophen, midazolam, and simvastatin (each given alone and together with orforglipron) that enters the bloodstream and how long it takes the body to eliminate them when administered orally in healthy overweight and obese participants. In addition, the effect of the orforglipron tablet on the amount of simvastatin that enters the bloodstream and how long it takes the body to eliminate it will be evaluated.

The study will also assess the effect of sodium bicarbonate when administered alone with simvastatin versus orforglipron capsule containing sodium bicarbonate administered with simvastatin. The safety and tolerability of orforglipron and information about any side effects experienced will be collected.

Study will be conducted in two parts, with part 1 and 2 lasting up to approximately 23 and 24 weeks each, including the screening period.

Conditions: Healthy, Obese, Overweight
Being tested: Orforglipron, Simvastatin, Digoxin, Rosuvastatin, Acetaminophen
Medical subject headings: Obesity, Overweight

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OrforglipronDrug
Also called LY3502970
Administered orally.
SimvastatinDrug
Administered orally.
DigoxinDrug
Administered orally.
RosuvastatinDrug
Administered orally.
AcetaminophenDrug
Administered orally.
MidazolamDrug
Administered orally.
Sodium BicarbonateDrug
Administered orally.

Study groups in NCT06186622
Study group	Role	What they receive
Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration	Experimental	Participants received single oral doses as follows:Day 1: 20 milligram(mg) simvastatin; Day 2: 0.25 mg digoxin; Day 7:20 mg simvastatin + 600 mg sodium bicarbonate; Day 8: 20 mg rosuvastatin; Day 10: 1000 mg acetaminophen; Day 12: 0.2 mg midazolam;Day 14: 1 mg Orforglipron, followed by 1000 mg acetaminophen administered 2 hours (±10 minutes) later (staggered); Day 15: 1 mg Orforglipron; Days 16-97: Orforglipron administered once daily with dose escalation every 14 days:1 mg (Days 16-27), 3 mg (Days 28-41),6 mg (Days 42-55),12 mg (Days 56-69),24 mg (Days 70-83),36 mg (Days 84-97). Days 98-110: 36 mg Orforglipron administered once daily with co administration as follows:Day 98: 20 mg simvastatin (simultaneous); Day 99: 0.25 mg digoxin (simultaneous); Day 104: 20 mg simvastatin (staggered); Day 105:20 mg rosuvastatin (simultaneous); Day 107: 1000 mg acetaminophen (staggered); Day 109:0.2 mg midazolam (simultaneous); Day 111: 20 mg Orforglipron tablet + 20 mg simvastatin (simultaneous). Receives: Drug: Orforglipron; Drug: Simvastatin; Drug: Digoxin; Drug: Rosuvastatin; Drug: Acetaminophen; Drug: Midazolam; Drug: Sodium Bicarbonate
Cohort 2: Oral Drug Dosing With or Without Orforglipron Co-Administration	Experimental	Participants received single oral doses as follows: Day 1: 20 mg Simvastatin; Day 2: 0.25 mg Digoxin; Day 7: 20 mg Simvastatin + 600 mg Sodium Bicarbonate; Day 9: 1 mg Orforglipron capsule; Days 10-90: Participants received orforglipron capsule orally QD for 12 weeks, beginning at 1 mg QD. The dose was escalated every 14 days as follows: 1 mg (Days 10-22), 3 mg (Days 23-36), 6 mg (Days 37-50), 12 mg (Days 51-64), 24 mg (Days 65-78), and 36 mg (Days 79-90). Participants continued 36 mg Orforglipron QD until Day 100, with co-administration of the following drugs; Day 93: 20 mg Simvastatin (simultaneous); Day 94: 0.25 mg Digoxin (simultaneous); Day 99: 20 mg Simvastatin administered 2 hours ±10 minutes after Orforglipron administration (staggered dosing); Day 101: 20 mg Orforglipron tablet + 20 mg Simvastatin (simultaneous) Receives: Drug: Orforglipron; Drug: Simvastatin; Drug: Digoxin; Drug: Sodium Bicarbonate

What is being measured

The primary outcome is the main question the study is designed to answer.

Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Simvastatin and Its Metabolite Simvastatin Acid Following Simultaneous Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
AUC [0-∞] of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.
Measured: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (h) post-dose; Day 98 (Cohort 1) and Day 93 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
AUC [0-∞] of simvastatin and its active acid metabolite (simvastatin acid) following staggered administration with or without Orforglipron capsule were reported in this outcome measure. Simvastatin was administered ~2h (±10 min) after Orforglipron capsule administration (Staggered dosing).
Measured: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 104 (Cohort 1) and Day 99 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2)
AUC [0-∞] of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without sodium bicarbonate administration were reported in this outcome measure.
Measured: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 7 (Cohort 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
PK: AUC [0-∞] of Digoxin (Cohort 1 and 2)
Measured: Day 2 (For Cohort 1 and 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose ; Day 99 (Cohort 1) and Day 94 (Cohort 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose
PK: AUC [0-∞] of Rosuvastatin (Cohort 1 Only)
Measured: Day 8 (Cohort 1 only): Pre-dose, 0.5, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72h post-dose; Day 105 (Cohort 1 only): Pre-dose, 0.5, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72h post-dose
PK: AUC [0-∞] of Acetaminophen (Cohort 1 Only)
AUC [0-∞] of acetaminophen following staggered administration with or without either 1 mg or 36 mg Orforglipron capsule were reported in this outcome measure. Acetaminophen was administered ~2h (±10 min) after Orforglipron capsule administration (Staggered dosing).
Measured: Day 10 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose; Day 14 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose; Day 107 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose
PK: AUC [0-∞] of Midazolam and Its Metabolite 1'-Hydroxymidazolam (Cohort 1 Only)
AUC [0-∞] of midazolam and its metabolite (1'-Hydroxymidazolam) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.
Measured: Day 12 (Cohort 1 only): Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, and 24h post-dose; Day 109 (Cohort 1 only): Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, and 24h post-dose
PK: Maximum Observed Concentration (Cmax) of Simvastatin and Its Metabolite Simvastatin Acid Following Simultaneous Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.
Measured: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 98 (Cohort 1) and Day 93 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
Cmax of simvastatin and its active acid metabolite (simvastatin acid) following staggered administration with or without Orforglipron capsule were reported in this outcome measure. Simvastatin was administered ~2h (±10 min) after Orforglipron capsule administration (Staggered dosing).
Measured: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 104 (Cohort 1) and Day 99 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2)
Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without sodium bicarbonate administration were reported in this outcome measure.
Measured: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 7 (Cohort 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
PK: Cmax of Digoxin (Cohorts 1 and 2)
Measured: Day 2 (For Cohort 1 and 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose; Day 99 (Cohort 1) and Day 94 (Cohort 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose
PK: Cmax of Rosuvastatin (Cohort 1 Only)
Measured: Day 8 (Cohort 1 only): Pre-dose, 0.5, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72h post-dose; Day 105 (Cohort 1 only): Pre-dose, 0.5, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72h post-dose
PK: Cmax of Acetaminophen (Cohort 1 Only)
Cmax of acetaminophen following staggered administration with or without either 1 mg or 36 mg Orforglipron capsule were reported in this outcome measure. Acetaminophen was administered ~2h (±10 min) after Orforglipron capsule administration (Staggered dosing).
Measured: Day 10 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose; Day 14 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose; Day 107 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose
PK: Cmax of Midazolam and Its Metabolite 1'-Hydroxymidazolam (Cohort 1 Only)
Cmax of Midazolam and its metabolite (1'-Hydroxymidazolam) following simultaneous administration with or without Orforglipron capsule is reported in this outcome measure.
Measured: Day 12 (Cohort 1 only): Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, and 24h post-dose; Day 109 (Cohort 1 only): Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, and 24h post-dose

Secondary outcomes (2)

PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Administration of Orforglipron Tablet Formulation (Cohort 1 and 2)
AUC [0-∞] of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron tablet were reported in this outcome measure.
Measured: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 111 (Cohort 1) and Day 101 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid Following Administration of Orforglipron Tablet Formulation (Cohort 1 and 2)
Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron tablet were reported in this outcome measure.
Measured: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 111 (Cohort 1) and Day 101 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Jan 202410 Jul 2024

First posted2 Jan 2024
Study start2 Jan 2024
Primary completion10 Jul 2024
Study completion10 Jul 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06186622
Sponsor's protocol ID: 18631
Other IDs: J2A-MC-GZPG
Status last verified: Apr 2026
First submitted: 16 Dec 2023
Last updated: 22 May 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Drug-Drug Interaction Study to Assess the Effect of Orforglipron on the Pharmacokinetics of Digoxin, Simvastatin, Rosuvastatin, Acetaminophen, and Midazolam in Healthy Overweight and Obese Participants
ClinicalTrials.gov ID: NCT06186622
Acronym / sponsor ID: 18631
Conditions: Healthy, Obese, Overweight
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 50 participants (actual)
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Study start: 2 Jan 2024 (actual)
Primary completion: 10 Jul 2024 (actual)
Study completion: 10 Jul 2024 (actual)
First posted: 2 Jan 2024 (actual)
Results: Posted 22 May 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study will be conducted in two parts, with part 1 and 2 lasting up to approximately 23 and 24 weeks each, including the screening period.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration	Experimental	Drug: Orforglipron, Drug: Simvastatin, Drug: Digoxin, Drug: Rosuvastatin, Drug: Acetaminophen, Drug: Midazolam, Drug: Sodium BicarbonateParticipants received single oral doses as follows:Day 1: 20 milligram(mg) simvastatin; Day 2: 0.25 mg digoxin; Day 7:20 mg simvastatin + 600 mg sodium bicarbonate; Day 8: 20 mg rosuvastatin; Day 10: 1000 mg acetaminophen; Day 12: 0.2 mg midazolam;Day 14: 1 mg Orforglipron, followed by 1000 mg acetaminophen administered 2 hours (±10 minutes) later (staggered); Day 15: 1 mg Orforglipron; Days 16-97: Orforglipron administered once daily with dose escalation every 14 days:1 mg (Days 16-27), 3 mg (Days 28-41),6 mg (Days 42-55),12 mg (Days 56-69),24 mg (Days 70-83),36 mg (Days 84-97). Days 98-110: 36 mg Orforglipron administered once daily with co administration as follows:Day 98: 20 mg simvastatin (simultaneous); Day 99: 0.25 mg digoxin (simultaneous); Day 104: 20 mg simvastatin (staggered); Day 105:20 mg rosuvastatin (simultaneous); Day 107: 1000 mg acetaminophen (staggered); Day 109:0.2 mg midazolam (simultaneous); Day 111: 20 mg Orforglipron tablet + 20 mg simvastatin (simultaneous).
Cohort 2: Oral Drug Dosing With or Without Orforglipron Co-Administration	Experimental	Drug: Orforglipron, Drug: Simvastatin, Drug: Digoxin, Drug: Sodium BicarbonateParticipants received single oral doses as follows: Day 1: 20 mg Simvastatin; Day 2: 0.25 mg Digoxin; Day 7: 20 mg Simvastatin + 600 mg Sodium Bicarbonate; Day 9: 1 mg Orforglipron capsule; Days 10-90: Participants received orforglipron capsule orally QD for 12 weeks, beginning at 1 mg QD. The dose was escalated every 14 days as follows: 1 mg (Days 10-22), 3 mg (Days 23-36), 6 mg (Days 37-50), 12 mg (Days 51-64), 24 mg (Days 65-78), and 36 mg (Days 79-90). Participants continued 36 mg Orforglipron QD until Day 100, with co-administration of the following drugs; Day 93: 20 mg Simvastatin (simultaneous); Day 94: 0.25 mg Digoxin (simultaneous); Day 99: 20 mg Simvastatin administered 2 hours ±10 minutes after Orforglipron administration (staggered dosing); Day 101: 20 mg Orforglipron tablet + 20 mg Simvastatin (simultaneous)

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Participants who are overtly healthy as determined by medical history and physical examination.
Have body mass index (BMI) equal to or greater than 27 kilograms per meter squared (kg/m²), inclusive, at screening.
Have an estimated glomerular filtration rate equal to or greater than 60 milliliters per minute (mL/min).
Males and females who agree to follow contraceptive requirements, or women not of childbearing potential (WNOCBP).
Have venous access sufficient to allow for blood sampling.

Key exclusion criteria (10 listed)

Have any type of diabetes with hemoglobin A1c (HbA1c) level of 6.5 percent (%) or greater.
Have significant history of or currently have Major Depressive Disorder or psychiatric disorder within the last 2 years.
Obesity induced by other endocrine disorders, such as Cushing's syndrome or Prader-Willi syndrome.
Have known clinically significant gastric emptying abnormality.
Have undergone bariatric surgery (for example: Lap-Band, Gastric Bypass)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OrforglipronAlso: LY3502970Administered orally.	Drug	Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration, Cohort 2: Oral Drug Dosing With or Without Orforglipron Co-Administration
SimvastatinAdministered orally.	Drug	Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration, Cohort 2: Oral Drug Dosing With or Without Orforglipron Co-Administration
DigoxinAdministered orally.	Drug	Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration, Cohort 2: Oral Drug Dosing With or Without Orforglipron Co-Administration
RosuvastatinAdministered orally.	Drug	Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration
AcetaminophenAdministered orally.	Drug	Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration
MidazolamAdministered orally.	Drug	Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration
Sodium BicarbonateAdministered orally.	Drug	Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration, Cohort 2: Oral Drug Dosing With or Without Orforglipron Co-Administration

Primary outcome

Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Simvastatin and Its Metabolite Simvastatin Acid Following Simultaneous Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (h) post-dose; Day 98 (Cohort 1) and Day 93 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
AUC [0-∞] of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.
PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 104 (Cohort 1) and Day 99 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
AUC [0-∞] of simvastatin and its active acid metabolite (simvastatin acid) following staggered administration with or without Orforglipron capsule were reported in this outcome measure. Simvastatin was administered ~2h (±10 min) after Orforglipron capsule administration (Staggered dosing).
PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2)
Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 7 (Cohort 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
AUC [0-∞] of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without sodium bicarbonate administration were reported in this outcome measure.
PK: AUC [0-∞] of Digoxin (Cohort 1 and 2)
Time frame: Day 2 (For Cohort 1 and 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose ; Day 99 (Cohort 1) and Day 94 (Cohort 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose
PK: AUC [0-∞] of Rosuvastatin (Cohort 1 Only)
Time frame: Day 8 (Cohort 1 only): Pre-dose, 0.5, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72h post-dose; Day 105 (Cohort 1 only): Pre-dose, 0.5, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72h post-dose
PK: AUC [0-∞] of Acetaminophen (Cohort 1 Only)
Time frame: Day 10 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose; Day 14 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose; Day 107 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose
AUC [0-∞] of acetaminophen following staggered administration with or without either 1 mg or 36 mg Orforglipron capsule were reported in this outcome measure. Acetaminophen was administered ~2h (±10 min) after Orforglipron capsule administration (Staggered dosing).
PK: AUC [0-∞] of Midazolam and Its Metabolite 1'-Hydroxymidazolam (Cohort 1 Only)
Time frame: Day 12 (Cohort 1 only): Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, and 24h post-dose; Day 109 (Cohort 1 only): Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, and 24h post-dose
AUC [0-∞] of midazolam and its metabolite (1'-Hydroxymidazolam) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.
PK: Maximum Observed Concentration (Cmax) of Simvastatin and Its Metabolite Simvastatin Acid Following Simultaneous Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 98 (Cohort 1) and Day 93 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.
PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)
Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 104 (Cohort 1) and Day 99 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
Cmax of simvastatin and its active acid metabolite (simvastatin acid) following staggered administration with or without Orforglipron capsule were reported in this outcome measure. Simvastatin was administered ~2h (±10 min) after Orforglipron capsule administration (Staggered dosing).
PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2)
Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 7 (Cohort 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without sodium bicarbonate administration were reported in this outcome measure.
PK: Cmax of Digoxin (Cohorts 1 and 2)
Time frame: Day 2 (For Cohort 1 and 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose; Day 99 (Cohort 1) and Day 94 (Cohort 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose
PK: Cmax of Rosuvastatin (Cohort 1 Only)
Time frame: Day 8 (Cohort 1 only): Pre-dose, 0.5, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72h post-dose; Day 105 (Cohort 1 only): Pre-dose, 0.5, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, and 72h post-dose
PK: Cmax of Acetaminophen (Cohort 1 Only)
Time frame: Day 10 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose; Day 14 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose; Day 107 (Cohort 1 only): Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24h post-dose
Cmax of acetaminophen following staggered administration with or without either 1 mg or 36 mg Orforglipron capsule were reported in this outcome measure. Acetaminophen was administered ~2h (±10 min) after Orforglipron capsule administration (Staggered dosing).
PK: Cmax of Midazolam and Its Metabolite 1'-Hydroxymidazolam (Cohort 1 Only)
Time frame: Day 12 (Cohort 1 only): Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, and 24h post-dose; Day 109 (Cohort 1 only): Pre-dose, 0.5, 0.75, 1, 2, 3, 4, 6, 9, 12, and 24h post-dose
Cmax of Midazolam and its metabolite (1'-Hydroxymidazolam) following simultaneous administration with or without Orforglipron capsule is reported in this outcome measure.

2 secondary outcomes

PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Administration of Orforglipron Tablet Formulation (Cohort 1 and 2)
Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 111 (Cohort 1) and Day 101 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose
PK: Cmax of Simvastatin and Its Metabolite Simvastatin Acid Following Administration of Orforglipron Tablet Formulation (Cohort 1 and 2)
Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 111 (Cohort 1) and Day 101 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose

Results and safety

Results posted to the registry on 22 May 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: Oral Drug Dosing With or Without Orforglipron Co-Administration	30	22
Cohort 2: Oral Drug Dosing With or Without Orforglipron Co-Administration	20	16

Primary outcome: Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Simvastatin and Its Metabolite Simvastatin Acid Following Simultaneous Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)

Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (h) post-dose; Day 98 (Cohort 1) and Day 93 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: Nanogram* hours per milliliter (ng*h/ml)

Measure	20 mg Simvastatin Alone n = 50	Simultaneous 36 mg Orforglipron Capsule + 20 mg Simvastatin n = 36
Simvastatin	22.1 (79.2)	18.8 (84.3)
Metabolite- Simvastatin Acid	13.6 (79.7)	23.3 (74.2)

Population analysed: All participants who received at least 1 dose of study drug and had evaluable PK data for this specific outcome. As pre-specified in Statistical Analysis Plan, participants were analyzed according to the treatment regimen they received. Data from Cohorts 1 and 2 were combined, and the pooled results are presented for this outcome measure.

Primary outcome: PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid Following Staggered Administration of Orforglipron Capsule Formulation (Cohort 1 and 2)

Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 104 (Cohort 1) and Day 99 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/ml

Measure	20 mg Simvastatin Alone n = 50	Staggered 36 mg Orforglipron Capsule + 20 mg Simvastatin n = 37
Simvastatin	22.1 (79.2)	20.1 (76.5)
Metabolite- Simvastatin Acid	13.6 (79.7)	30.2 (70.3)

Population analysed: All participants who received at least 1 dose of study drug and had evaluable PK data. As pre-specified in Statistical Analysis Plan, participants were analyzed according to the treatment regimen they received. Data from Cohorts 1 and 2 were combined, and the pooled results are presented for this outcome measure.

Primary outcome: PK: AUC [0-∞] of Simvastatin and Its Metabolite Simvastatin Acid After Sodium Bicarbonate Coadministration (Cohort 1 and 2)

Time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose; Day 7 (Cohort 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/ml

Measure	20 mg Simvastatin Alone n = 50	20 mg Simultaneous Simvastatin + 600 mg Sodium Bicarbonate n = 47
Simvastatin	22.1 (79.2)	20.3 (82.8)
Metabolite- Simvastatin Acid	13.6 (79.7)	14.0 (61.3)

Primary outcome: PK: AUC [0-∞] of Digoxin (Cohort 1 and 2)

Time frame: Day 2 (For Cohort 1 and 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose ; Day 99 (Cohort 1) and Day 94 (Cohort 2): Pre-dose, 0.5, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, and 120h post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/ml

Measure	0.25 mg Digoxin Alone n = 50	Simultaneous 36 mg Orforglipron Capsule + 0.25 mg Digoxin n = 37
Value	18.8 (21.5)	22.4 (26.5)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Cohort 1: Baseline up to end of follow-up (up to 129 days); Cohort 2: Baseline up to end of follow-up (up to 119 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: 20 mg Simvastatin Alone (Day 1)	0 of 30 (0%)	2 of 30 (6.7%)	0 of 30
Cohort 1: 0.25 mg Digoxin Alone (Day 2)	0 of 30 (0%)	0 of 30 (0%)	0 of 30
Cohort 1: 20 mg Simvastatin + 600 mg Sodium Bicarbonate (Day 7)	0 of 28 (0%)	0 of 28 (0%)	0 of 28
Cohort 1: 20 mg Rosuvastatin Alone (Day 8)	0 of 28 (0%)	0 of 28 (0%)	0 of 28
Cohort 1: 1000 mg Acetaminophen Alone (Day 10)	0 of 27 (0%)	1 of 27 (3.7%)	0 of 27
Cohort 1: 0.2 mg Midazolam Alone (Day 12)	0 of 27 (0%)	0 of 27 (0%)	0 of 27
Cohort 1: Staggered 1 mg Orforglipron Capsule + 1000 mg Acetaminophen (Day 14)	0 of 27 (0%)	1 of 27 (3.7%)	0 of 27
Cohort 1: 1 mg Orforglipron Capsule QD (Day 15 to Day 27)	0 of 27 (0%)	4 of 27 (14.8%)	0 of 27
Cohort 1: 3 mg Orforglipron Capsule QD (Day 28 to Day 41)	0 of 26 (0%)	2 of 26 (7.7%)	0 of 26
Cohort 1: 6 mg Orforglipron Capsule QD (Day 42 to Day 55)	0 of 26 (0%)	5 of 26 (19.2%)	0 of 26
Cohort 1: 12 mg Orforglipron Capsule QD (Day 56 to Day 69)	0 of 26 (0%)	2 of 26 (7.7%)	0 of 26
Cohort 1: 24 mg Orforglipron Capsule QD (Day 70 to Day 83)	0 of 26 (0%)	2 of 26 (7.7%)	0 of 26
Cohort 1: 36 mg Orforglipron Capsule QD (Day 84 to Day 97)	0 of 26 (0%)	11 of 26 (42.3%)	0 of 26
Cohort 1: Simultaneous 36 mg Orforglipron Capsule + 20 mg Simvastatin (Day 98)	0 of 22 (0%)	0 of 22 (0%)	0 of 22
Cohort 1: Simultaneous 36 mg Orforglipron Capsule + 0.25 mg Digoxin (Day 99)	0 of 22 (0%)	2 of 22 (9.1%)	0 of 22
Cohort 1: 36 mg Orforglipron Capsule QD (Day 100 to Day 103)

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) study director

Eli Lilly and Company

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Orforglipron, Simvastatin and Digoxin in people with Healthy and Obese, run by Eli Lilly and Company at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Simvastatin and Its Metabolite Simvastatin Acid Following Simultaneous Administration of Orforglipron Capsule Formulation (Cohort 1 and 2) (time frame: Day 1 (For Cohorts 1 and 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (h) post-dose; Day 98 (Cohort 1) and Day 93 (Cohort 2): Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24h post-dose). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06186622.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.