Type 2 Diabetes
Conditions
Brief summary
The main purpose of this study is to assess efficacy and safety of orforglipron compared with oral semaglutide in participants with Type 2 diabetes and inadequate glycemic control with metformin.The study will last around 61 weeks.
Interventions
DRUGOrforglipron
Administered orally
DRUGSemaglutide
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have Type 2 Diabetes * Have HbA1c ≥7.0% (53 mmol/mol) to ≤10.5% (91 mmol/mol), as determined by the central laboratory at screening. * Have been on stable diabetes treatment with metformin ≥1500 milligram (mg)/day during the 90 days prior to screening and maintained through randomization. * Are of stable body weight (±5%) for at least 90 days prior to screening and agree to not initiate an intensive diet or exercise program during the study with the intent of reducing body weight, other than the lifestyle and/or dietary measures for diabetes treatment
Exclusion criteria
* Have Type 1 Diabetes * Are currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema, for example, laser photocoagulation or intravitreal injections of anti-vascular endothelial growth factor inhibitors. * Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening, or between screening and randomization. * Have a New York Heart Association functional classification IV congestive heart failure. * Have an estimated glomerular filtration rate (eGFR) \<45 milliliter/minute (mL/min)/1.73 square meter (m²) or lower than the country-specific threshold for discontinuing metformin therapy per local label as determined by the central laboratory at screening. * Have a serum calcitonin level of ≥35 nanogram/Liter (ng/L), as determined by the central laboratory at screening. * Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) [Non-inferiority of 36 mg Orforglipron Versus 14 mg Semaglutide and 12 mg Orforglipron Versus 7 mg Semaglutide] | Baseline, Week 52 | * HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. * LS mean was analysed by mixed model repeated measures (MMRM) model with Country + Baseline\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) [Non-inferiority of 12 mg Orforglipron Versus 14 mg Semaglutide, Superiority of 12 mg and 36 mg Orforglipron Versus 7 mg and 14 mg Semaglutide] | Baseline, Week 52 | * HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. * LS mean was analysed by mixed model repeated measures (MMRM) model with Country + Baseline\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Percentage of Participants Who Achieved HbA1c <7.0% [53 Millimoles/Mole (mmol/Mol)] | Week 52 | The reported values represent model-based group mean percentages estimated from a logistic regression model using imputed data, with estimates combined across multiple imputations using Rubin's rule. Logistic regression model variables: Country + Treatment\*Baseline + Treatment\*Strata (defined by baseline HbA1c level \[\<=8.0%, \>8.0%\]). |
| Percentage of Participants Who Achieved HbA1c <=6.5% (48 mmol/Mol) | Week 52 | The reported values represent model-based group mean percentages estimated from a logistic regression model using imputed data, with estimates combined across multiple imputations using Rubin's rule. Logistic regression model variables: Country + Treatment\*Baseline + Treatment\*Strata (defined by baseline HbA1c level \[\<=8.0%, \>8.0%\]). |
| Percentage of Participants Who Achieved HbA1c <5.7% (39 mmol/Mol) | Week 52 | The reported values represent model-based group mean percentages estimated from a logistic regression model using imputed data, with estimates combined across multiple imputations using Rubin's rule. Logistic regression model variables: Country + Treatment\*Baseline + Treatment\*Strata (defined by baseline HbA1c level \[\<=8.0%, \>8.0%\]). |
| Percent Change From Baseline in Body Weight | Baseline, Week 52 | LS mean was analysed by MMRM model with Country + Baseline\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Change From Baseline in Body Weight | Baseline, Week 52 | LS mean was analysed by MMRM model with Country + Baseline\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Change From Baseline in Fasting Serum Glucose | Baseline, Week 52 | LS mean was analysed by MMRM model with Country + Baseline\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose (SMBG) | Baseline, Week 52 | The SMBG data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Post meal, Midday Premeal, Midday 2-hour Post meal, Evening Premeal, Evening 2-hour Post meal and Bedtime. The daily average was calculated as the average of the 7 blood glucose values collected on a particular day. LS mean was analysed by MMRM model with Country + Baseline\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Percentage of Participants Who Achieved Weight Loss of >=5% | Week 52 | The reported values represent model-based group mean percentages estimated from a logistic regression model using imputed data, with estimates combined across multiple imputations using Rubin's rule. Logistic regression model variables: Country + Treatment\*Baseline + Treatment\*Strata (defined by baseline HbA1c level \[\<=8.0%, \>8.0%\]). |
| Percentage of Participants Who Achieved Weight Loss of >=10% | Week 52 | The reported values represent model-based group mean percentages estimated from a logistic regression model using imputed data, with estimates combined across multiple imputations using Rubin's rule. Logistic regression model variables: Country + Treatment\*Baseline + Treatment\*Strata (defined by baseline HbA1c level \[\<=8.0%, \>8.0%\]). |
| Percentage of Participants Who Achieved Weight Loss of >=15% | Week 52 | The reported values represent model-based group mean percentages estimated from a logistic regression model using imputed data, with estimates combined across multiple imputations using Rubin's rule. Logistic regression model variables: Country + Treatment\*Baseline + Treatment\*Strata (defined by baseline HbA1c level \[\<=8.0%, \>8.0%\]). |
| Change From Baseline in Systolic Blood Pressure (SBP) | Baseline, Week 52 | LS mean was analysed by MMRM model with Country + Baseline\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Change From Baseline in Diastolic Blood Pressure (DBP) | Baseline, Week 52 | LS mean was analysed by MMRM model with Country + Baseline\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Percent Change From Baseline in Total Serum Cholesterol | Baseline, Week 52 | LS mean was analysed by MMRM model with Country + log(Baseline)\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Percent Change From Baseline in Serum Low Density Lipoprotein (LDL) Cholesterol | Baseline, Week 52 | LS mean was analysed by MMRM model with Country + log(Baseline)\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Percent Change From Baseline in Serum Non High Density Lipoprotein (Non-HDL) Cholesterol | Baseline, Week 52 | LS mean was analysed by MMRM model with Country + log(Baseline)\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Percent Change From Baseline in Serum Triglycerides | Baseline, Week 52 | LS mean was analysed by MMRM model with Country + log(Baseline)\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Percent Change From Baseline in Serum High Density Lipoprotein (HDL) Cholesterol | Baseline, Week 52 | LS mean was analysed by MMRM model with Country + log(Baseline)\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Percent Change From Baseline in Serum Very Low Density Lipoprotein (VLDL) Cholesterol | Baseline, Week 52 | LS mean was analysed by MMRM model with Country + log(Baseline)\*Time\*Treatment + Strata\*Time\*Treatment as variables. Strata is defined by joint levels of HbA1c level (\<=8.0%, \>8.0%). |
| Change From Baseline in Short Form 36 Version 2 (SF-36-v2) Acute Form (Physical Component and Mental Component Scores) | Baseline, Week 52 | The SF-36v2 is a participant-reported measure designed to assess health status using 36 items across 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The physical functioning domain assesses limitations due to health "now," whereas the remaining domains assess functioning "in the past week." Each domain is scored individually, and information from these 8 domains is aggregated into 2 health component summary scores, the physical component summary and mental component summary. Items are answered on Likert scales of varying lengths (3-point, 5-point, or 6-point scales). Scoring of each domain and both summary scores are norm based and presented in the form of T-scores, with a mean of 50 and a standard deviation of 10. Higher scores indicate better levels of function and/or better health. Range cannot be specified in norm-based scores. |
Countries
Argentina, China, Japan, Mexico, Puerto Rico, United States
Contacts
STUDY_DIRECTORCall 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)
Eli Lilly and Company
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 54.0 years STANDARD_DEVIATION 11.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1234 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 455 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| HemoglobinA1c (HbA1c) | 8.29 Percentage of HbA1c STANDARD_DEVIATION 1.09 |
| Race (NIH/OMB) American Indian or Alaska Native | 89 Participants |
| Race (NIH/OMB) Asian | 202 Participants |
| Race (NIH/OMB) Black or African American | 65 Participants |
| Race (NIH/OMB) More than one race | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) White | 250 Participants |
| Region of Enrollment Argentina | 582 Participants |
| Region of Enrollment China | 25 Participants |
| Region of Enrollment Japan | 20 Participants |
| Region of Enrollment Mexico | 123 Participants |
| Region of Enrollment United States | 110 Participants |
| Sex: Female, Male Female | 218 Participants |
| Sex: Female, Male Male | 219 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 424 | 1 / 423 | 2 / 426 | 0 / 425 |
| other Total, other adverse events | 278 / 424 | 278 / 423 | 225 / 426 | 249 / 425 |
| serious Total, serious adverse events | 21 / 424 | 40 / 423 | 19 / 426 | 24 / 425 |
Outcome results
None listed