Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Orforglipron · 31 trials · 30 indications
Composite endpoint includes nonfatal myocardial infarction, nonfatal stroke, hospitalization or urgent visit due to heart failure, coronary revascularization, or all-cause death
On a constant load treadmill test
A TEAE was defined as any adverse event that began on or after the first dose of study drug or began before the first dose of study drug and worsened on or after the first dose of study drug.
* Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A, measured to reflect average plasma glucose concentration over prolonged periods of time. * Values represented under "Least Squares (LS) Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a mixed-model repeated measures (MMRM) with analysis country, treatment by time, baseline by time by treatment, and strata by time by treatment in the model. Strata was defined by joint levels of baseline HbA1c (≤ \[less than or equal to\] 8.0%, \> \[greater than\] 8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured.
Values reported as "LS Mean" are model-based estimates (MBE) of the adjusted (unconditional) treatment effect. MBEs was calculated using an analysis of covariance (ANCOVA) model with the following variables: treatment group, baseline value, baseline Body Mass Index (BMI) category (\<35 kilogram per meter square \[kg/m²\] or ≥35 kg/m²), and stratification factors (sex and baseline type 2 diabetes status). Strata were defined by joint levels of sex (female, male) and baseline type 2 diabetes status (yes, no).
Percentage of participants with ≥5% body weight reduction was analysed by Logistic regression with the following variables: treatment group, baseline value, baseline BMI category (\<35 kg/m² or ≥35 kg/m²), and stratification factors (sex and baseline type 2 diabetes status). Stratification factors were defined by the combination of sex (female, male) and baseline type 2 diabetes status (yes, no). The model also allowed the treatment effect to vary across baseline values and stratification factors.
Time to First Occurrence of Any MACE-4 (Myocardial Infarction (MI), Stroke, Hospitalization for Unstable Angina, or Cardiovascular \[CV\] Death)
PK: Steady-state AUC of Orforglipron (Fasted State)
PK: Steady-state Cmax of Orforglipron (Fasted State)
PK: AUC0-inf of Orforglipron.
PK: Cmax of Orforglipron.
PK: Area under the concentration versus time curve from time 0 to the end of the once daily dosing interval at steady state AUC\[0-tau\] on Day 7.
PK: Maximum concentration of LY3502970 during a once daily dosing interval at steady state on Day 7.
PK: AUC (0-∞) of Orforglipron
PK: AUC (0-tlast) of Orforglipron
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.
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).
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.
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).
AUC \[0-∞\] of midazolam and its metabolite (1'-Hydroxymidazolam) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.
Cmax of simvastatin and its active acid metabolite (simvastatin acid) following simultaneous administration with or without Orforglipron capsule were reported in this outcome measure.
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).
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.
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).
Cmax of Midazolam and its metabolite (1'-Hydroxymidazolam) following simultaneous administration with or without Orforglipron capsule is reported in this outcome measure.
| Arm | Type | Description |
|---|---|---|
| Orforglipron | EXPERIMENTAL | Participants will receive orforglipron orally |
| Dulaglutide | ACTIVE_COMPARATOR | Participants will receive dulaglutide subcutaneously (SC) |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo orally + standard of care |
| Orforglipron (GZS1) | EXPERIMENTAL | Participants will receive orforglipron orally |
| Placebo (GZS1) | PLACEBO_COMPARATOR | Participants will receive placebo orally |
| Orforglipron (GZS2) | EXPERIMENTAL | Participants will receive orforglipron orally |
| Placebo (GZS2) | PLACEBO_COMPARATOR | Participants will receive placebo orally |
| Orforglipron (GZT1) | EXPERIMENTAL | Participants will receive orforglipron orally |
| Placebo (GZT1) | PLACEBO_COMPARATOR | Participants will receive placebo orally |
| Orforglipron (GZT2) | EXPERIMENTAL | Participants will receive orforglipron orally |
| Placebo (GZT2) | PLACEBO_COMPARATOR | Participants will receive placebo orally |
| Orforglipron Dose 1 | EXPERIMENTAL | Participants will receive orforglipron orally |
| Orforglipron Dose 2 | EXPERIMENTAL | Participants will receive orforglipron orally |
| Orforglipron Dose 3 | EXPERIMENTAL | Participants will receive orforglipron orally |
| Orforglipron Dose 4 | EXPERIMENTAL | Participants will receive orforglipron orally |
| Orforglipron Dose 1 (Study GZP1) | EXPERIMENTAL | Participants will receive orforglipron orally |
| Orforglipron Dose 2 (Study GZP1) | EXPERIMENTAL | Participants will receive orforglipron orally |
| Orforglipron Dose 3 (Study GZP1) | EXPERIMENTAL | Participants will receive orforglipron orally |
| Orforglipron Dose 4 (Study GZP1) | EXPERIMENTAL | Participants will receive orforglipron orally |
| Placebo (Study GZP1) | PLACEBO_COMPARATOR | Participants will receive placebo orally |
| Orforglipron Dose 1 (Study GZP2) | EXPERIMENTAL | Participants will receive orforglipron orally |
| Orforglipron Dose 2 (Study GZP2) | EXPERIMENTAL | Participants will receive orforglipron orally |
| Orforglipron Dose 3 (Study GZP2) | EXPERIMENTAL | Participants will receive orforglipron orally |
| Orforglipron Dose 4 (Study GZP2) | EXPERIMENTAL | Participants will receive orforglipron orally |
| Placebo (Study GZP2) | PLACEBO_COMPARATOR | Participants will receive placebo orally |
| Orforglipron (GZL1) | EXPERIMENTAL | Participants will receive orforglipron orally or placebo. |
| Orforglipron (GZL2) | EXPERIMENTAL | Participants will receive orforglipron orally or placebo. |
| Orforglipron (ISA PW01) | EXPERIMENTAL | Participants will receive orforglipron or placebo orally. Each ISA will detail the intervention specific. |
| Dapagliflozin | ACTIVE_COMPARATOR | Participants will receive dapagliflozin orally. |
| 3 mg Orforglipron | EXPERIMENTAL | Participants received once-daily oral orforglipron for 52 weeks. Treatment began with a 1-mg loading dose for the first 4 weeks, followed by the maintenance dose of 3 mg for the remainder of the duration. |
| 12 mg Orforglipron | EXPERIMENTAL | Participants received once-daily oral orforglipron for 52 weeks. Treatment began with a 1-mg loading dose for the first 4 weeks, followed by dose escalations every 4 weeks to reach the maintenance dose of 12 mg at week 12, which was then continued for the remainder of the duration. |
| 36 mg Orforglipron | EXPERIMENTAL | Participants received once-daily oral orforglipron for 52 weeks. Treatment began with a 1-mg loading dose for the first 4 weeks, followed by dose escalations every 4 weeks to reach the maintenance dose of 36 mg at week 20, which was then continued for the remainder of the duration. |
| Semaglutide Dose 1 | ACTIVE_COMPARATOR | Participants will receive semaglutide orally. |
| Semaglutide Dose 2 | ACTIVE_COMPARATOR | Participants will receive semaglutide orally. |
| Placebo QD | PLACEBO_COMPARATOR | Participants received matching placebo capsule orally once daily (QD). Treatment was initiated with placebo corresponding to 1 mg equivalent to Orforglipron, with dose escalation every 4 weeks to maintain blinding, and was continued through Week 72, unless dose interruption or modification was required. Treatment was administered as an adjunct to a reduced-calorie diet and increased physical activity. |
| 6 mg Orforglipron QD | EXPERIMENTAL | Participants received oral orforglipron capsule once daily. Treatment was initiated at 1 mg once daily, with dose escalation every 4 weeks to a target dose of 6 mg, which was maintained through Week 72, unless dose interruption or modification was required. Treatment was administered as an adjunct to a reduced-calorie diet and increased physical activity. |
| 12 mg Orforglipron QD | EXPERIMENTAL | Participants received oral orforglipron capsule once daily. Treatment was initiated at 1 mg once daily, with dose escalation every 4 weeks to a target dose of 12 mg, which was maintained through Week 72, unless dose interruption or modification was required. Treatment was administered as an adjunct to a reduced-calorie diet and increased physical activity. |
| 36 mg Orforglipron QD | EXPERIMENTAL | Participants received oral orforglipron capsule once daily. Treatment was initiated at 1 mg once daily, with dose escalation every 4 weeks to a target dose of 36 mg, which was maintained through Week 72, unless dose interruption or modification was required. Treatment was administered as an adjunct to a reduced-calorie diet and increased physical activity. |
| Insulin Glargine | ACTIVE_COMPARATOR | Participants will receive insulin glargine subcutaneously (SC). Doses will be individualized and titrated according to a treat-to-target algorithm. |
| Midazolam + Orforglipron + Quinidine | EXPERIMENTAL | Participants received: * Day -1: single dose of 0.2 milligram (mg) midazolam. * Day 1: single dose of 1 mg orforglipron. * Days 5 to 6: 200 mg quinidine twice daily (BID). * Day 7: 200 mg quinidine BID plus a single dose of 0.2 mg midazolam. * Day 8: 200 mg quinidine BID plus a single dose of 1 mg orforglipron. |
| Part A: LY3502970 QD Oral Administration (Cohort 1A, Sequence 1) | EXPERIMENTAL | Participants received LY3502970 orally once daily (QD) across inpatient Treatment Periods 1-12 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: 1 mg (Capsule) * Period 2: Dose Level 2 (Tablet) * Period 3: Dose Level 1 (Tablet) * Period 4: Dose Level 3 (Tablet) * Period 5: 3 mg (Capsule) * Period 6: Dose Level 5 (Tablet) * Period 7: Dose Level 4 (Tablet) * Period 8: Dose Level 6 (Tablet) * Period 9: 6 mg (Capsule) * Period 10: Dose Level 8 (Tablet) * Period 11: Dose Level 7 (Tablet) * Period 12: Dose Level 9 (Tablet) |
| Part A: LY3502970 Oral Administration (Cohort 1A, Sequence 2) | EXPERIMENTAL | Participants received LY3502970 orally QD across inpatient Treatment Periods 1-12 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: Dose Level 2 (Tablet) * Period 2: 1 mg (Capsule) * Period 3: Dose Level 3 (Tablet) * Period 4: Dose Level 1 (Tablet) * Period 5: Dose Level 5 (Tablet) * Period 6: 3 mg (Capsule) * Period 7: Dose Level 6 (Tablet) * Period 8: Dose Level 4 (Tablet) * Period 9: Dose Level 8 (Tablet) * Period 10: 6 mg (Capsule) * Period 11: Dose Level 9 (Tablet) * Period 12: Dose Level 7 (Tablet) |
| Part A: LY3502970 Oral Administration (Cohort 1A, Sequence 3) | EXPERIMENTAL | Participants received LY3502970 orally QD across inpatient Treatment Periods 1-12 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: Dose Level 1 (Tablet) * Period 2: Dose Level 3 (Tablet) * Period 3: 1 mg (Capsule) * Period 4: Dose Level 2 (Tablet) * Period 5: Dose Level 4 (Tablet) * Period 6: Dose Level 6 (Tablet) * Period 7: 3 mg (Capsule) * Period 8: Dose Level 5 (Tablet) * Period 9: Dose Level 7 (Tablet) * Period 10: Dose Level 9 (Tablet) * Period 11: 6 mg (Capsule) * Period 12: Dose Level 8 (Tablet) |
| Part A: LY3502970 Oral Administration (Cohort 1A, Sequence 4) | EXPERIMENTAL | Participants received LY3502970 orally QD across inpatient Treatment Periods 1-12 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: Dose Level 3 (Tablet) * Period 2: Dose Level 1 (Tablet) * Period 3: Dose Level 2 (Tablet) * Period 4: 1 mg (Capsule) * Period 5: Dose Level 6 (Tablet) * Period 6: Dose Level 4 (Tablet) * Period 7: Dose Level 5 (Tablet) * Period 8: 3 mg (Capsule) * Period 9: Dose Level 9 (Tablet) * Period 10: Dose Level 7 (Tablet) * Period 11: Dose Level 8 (Tablet) * Period 12: 6 mg (Capsule) |
| Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 1) | EXPERIMENTAL | Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg and 6 mg; Capsule), followed by inpatient Treatment Periods 7-18 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: 12 mg (Capsule) * Period 8: Dose Level 11 (Tablet) * Period 9: Dose Level 10 (Tablet) * Period 10: Dose Level 12 (Tablet) * Period 11: 24 mg (Capsule) * Period 12: Dose Level 14 (Tablet) * Period 13: Dose Level 13 (Tablet) * Period 14: Dose Level 16 (Tablet) * Period 15: 36 mg (Capsule) * Period 16: Dose Level 17 (Tablet) * Period 17: Dose Level 15 (Tablet) * Period 18: Dose Level 18 (Tablet) |
| Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 2) | EXPERIMENTAL | Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg; Capsule), followed by inpatient Treatment Periods 7-18 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: Dose Level 11 (Tablet) * Period 8: 12 mg (Capsule) * Period 9: Dose Level 12 (Tablet) * Period 10: Dose Level 10 (Tablet) * Period 11: Dose Level 14 (Tablet) * Period 12: 24 mg (Capsule) * Period 13: Dose Level 16 (Tablet) * Period 14: Dose Level 13 (Tablet) * Period 15: Dose Level 17 (Tablet) * Period 16: 36 mg (Capsule) * Period 17: Dose Level 18 (Tablet) * Period 18: Dose Level 15 (Tablet) |
| Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 3) | EXPERIMENTAL | Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg and 6 mg; Capsule), followed by inpatient Treatment Periods 7-18 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: Dose Level 10 (Tablet) * Period 8: Dose Level 12 (Tablet) * Period 9: 12 mg (Capsule) * Period 10: Dose Level 11 (Tablet) * Period 11: Dose Level 13 (Tablet) * Period 12: Dose Level 16 (Tablet) * Period 13: 24 mg (Capsule) * Period 14: Dose Level 14 (Tablet) * Period 15: Dose Level 15 (Tablet) * Period 16: Dose Level 18 (Tablet) * Period 17: 36 mg (Capsule) * Period 18: Dose Level 17 (Tablet) |
| Part A: LY3502970 Oral Administration (Cohort 2A, Sequence 4) | EXPERIMENTAL | Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg; Capsule), followed by inpatient Treatment Periods 7-18 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: Dose Level 12 (Tablet) * Period 8: Dose Level 10 (Tablet) * Period 9: Dose Level 11 (Tablet) * Period 10: 12 mg (Capsule) * Period 11: Dose Level 16 (Tablet) * Period 12: Dose Level 13 (Tablet) * Period 13: Dose Level 14 (Tablet) * Period 14: 24 mg (Capsule) * Period 15: Dose Level 18 (Tablet) * Period 16: Dose Level 15 (Tablet) * Period 17: Dose Level 17 (Tablet) * Period 18: 36 mg (Capsule) |
| Part B: LY3502970 Oral Administration (Cohort 1B, Sequence 1) | EXPERIMENTAL | Participants received LY3502970 orally QD across inpatient Treatment Periods 1-9 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: 1 mg (Capsule- First Treatment) * Period 2: 1 mg (Capsule- Second Treatment) * Period 3: 0.8 mg (Tablet) * Period 4: 3 mg (Capsule- First Treatment) * Period 5: 3 mg (Capsule- Second Treatment) * Period 6: 2.5 mg (Tablet) * Period 7: 6 mg (Capsule- First Treatment) * Period 8: 6 mg (Capsule- Second Treatment) * Period 9: 5.5 mg (Tablet) |
| Part B: LY3502970 Oral Administration (Cohort 1B, Sequence 2) | EXPERIMENTAL | Participants received LY3502970 orally QD across inpatient Treatment Periods 1-9 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: 1 mg (Capsule- First Treatment) * Period 2: 0.8 mg (Tablet) * Period 3: 1 mg (Capsule- Second Treatment) * Period 4: 3 mg (Capsule- First Treatment) * Period 5: 2.5 mg (Tablet) * Period 6: 3 mg (Capsule- Second Treatment) * Period 7: 6 mg (Capsule- First Treatment) * Period 8: 5.5 mg (Tablet) * Period 9: 6 mg (Capsule- Second Treatment) |
| Part B: LY3502970 Oral Administration (Cohort 1B, Sequence 3) | EXPERIMENTAL | Participants received LY3502970 orally QD across inpatient Treatment Periods 1-9 (7 days per period), followed by a follow-up visit approximately 7 days after the last dose. Doses were administered as follows: * Period 1: 0.8 mg (Tablet) * Period 2: 1 mg (Capsule- First Treatment) * Period 3: 1 mg (Capsule- Second Treatment) * Period 4: 2.5 mg (Tablet) * Period 5: 3 mg (Capsule- First Treatment) * Period 6: 3 mg (Capsule- Second Treatment) * Period 7: 5.5 mg (Tablet) * Period 8: 6 mg (Capsule- First Treatment) * Period 9: 6 mg (Capsule- Second Treatment) |
| Part B: LY3502970 Oral Administration (Cohort 2B, Sequence 1) | EXPERIMENTAL | Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg \[Capsule\]), followed by inpatient Treatment Periods 7-15 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: 12 mg (Capsule- First Treatment) * Period 8: 12 mg (Capsule- Second Treatment) * Period 9: 9 mg (Tablet) * Period 10: 24 mg (Capsule- First Treatment) * Period 11: 24 mg (Capsule- Second Treatment) * Period 12: 14.5 mg (Tablet) * Period 13: 36 mg (Capsule- First Treatment) * Period 14: 36 mg (Capsule- Second Treatment) * Period 15: 17.2 mg (Tablet) |
| Part B: LY3502970 Oral Administration (Cohort 2B, Sequence 2) | EXPERIMENTAL | Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg \[Capsule\]), followed by inpatient Treatment Periods 7-15 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: 12 mg (Capsule- First Treatment) * Period 8: 9 mg (Tablet) * Period 9: 12 mg (Capsule- Second Treatment) * Period 10: 24 mg (Capsule- First Treatment) * Period 11: 14.5 mg (Tablet) * Period 12: 24 mg (Capsule- Second Treatment) * Period 13: 36 mg (Capsule- First Treatment) * Period 14: 17.2 mg (Tablet) * Period 15: 36 mg (Capsule- Second Treatment) |
| Part B: LY3502970 Oral Administration (Cohort 2B, Sequence 3) | EXPERIMENTAL | Participants received LY3502970 orally QD during home dosing Treatment Periods 1-6 (1 mg, 3 mg, and 6 mg \[Capsule\]), followed by inpatient Treatment Periods 7-15 (7 days per period) and a follow-up visit approximately 7 days after the last dose. Doses during inpatient periods were administered as follows: * Period 7: 9 mg (Tablet) * Period 8: 12 mg (Capsule- First Treatment) * Period 9: 12 mg (Capsule- Second Treatment) * Period 10: 14.5 mg (Tablet) * Period 11: 24 mg (Capsule- First Treatment) * Period 12: 24 mg (Capsule- Second Treatment) * Period 13: 17.2 mg (Tablet) * Period 14: 36 mg (Capsule- First Treatment) * Period 15: 36 mg (Capsule- Second Treatment) |
| Orforglipron + Carbamazepine | EXPERIMENTAL | Participants received study intervention through oral administration as follows: * Day 1: 1 milligram (mg) orforglipron capsule alone * Days 6 to 8: Twice daily (BID) doses of 100 mg carbamazepine tablets * Days 9 to 11: BID doses of 200 mg carbamazepine tablets * Days 12 to 14: BID doses of 300 mg carbamazepine tablets * Day 15: 1 mg orforglipron capsule co-administered with BID doses of 300 mg carbamazepine tablets * Days 16 to 18: BID doses of 300 mg carbamazepine tablets |
| 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). |
| 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) |
| Name | Type | Description |
|---|---|---|
| Orforglipron | DRUG | Administered orally |
| Dulaglutide | DRUG | Administered SC |
| Placebo | DRUG | Administered orally |
| Dapagliflozin | DRUG | Administered orally |
| Semaglutide | DRUG | Administered orally |
| Insulin Glargine | DRUG | Administered SC once daily |
| Midazolam | DRUG | Administered orally |
| Quinidine | DRUG | Administered orally |
| Carbamazepine | DRUG | Administered orally |
| Simvastatin | DRUG | Administered orally. |
| Digoxin | DRUG | Administered orally. |
| Rosuvastatin | DRUG | Administered orally. |
| Acetaminophen | DRUG | Administered orally. |
| Sodium Bicarbonate | DRUG | Administered orally. |
Inclusion Criteria: * Have type 2 diabetes treated with diet and exercise and metformin and/or basal insulin * Have HbA1c \> 6.5% to ≤ 11.0% at screening * Have a body weight ≥50 kilograms (kg) (110 pounds) and a body mass index (BMI) of \>85th percentile Exclusion Criteria: * Have type 1 diabete...