Type 2 Diabetes
Conditions
Brief summary
The main purpose of this study is to determine safety and efficacy of orforglipron compared with placebo in adult participants with type 2 diabetes and inadequate glycemic control with diet and exercise alone. The study will last approximately 54 weeks.
Interventions
DRUGOrforglipron
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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 ≤9.5% (80 mmol/mol) despite diet and exercise treatment, as determined by the central laboratory at screening. * Are naïve to insulin therapy except for gestational diabetes or ≤14 days use for acute treatment and have not used any oral or injectable antihyperglycemic medications during the 90 days preceding screening or between screening and randomization. * Are of stable 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. * Have a body mass index (BMI) ≥23.0 kilogram/square meter (kg/m²) at screening.
Exclusion criteria
* Have Type 1 Diabetes * Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening, or between screening and randomization. * Currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema * Have New York Heart Association functional classification IV congestive heart failure. * Have acute or chronic pancreatitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c | Baseline, Week 40 | * 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an HbA1c Target Value of < 7.0% (53 mmol/Mol) | Week 40 | Percentage of participants with an HbA1c target value of less than (\<) 7.0% (53 millimoles per mole \[mmol/mol\]) was analysed by Logistic regression with analysis country, treatment by baseline and treatment by strata in the model. Strata were defined by joint levels of baseline HbA1c (≤8.0%, \>8.0%) and prior use of any antihyperglycemic medication (yes or no). |
| Percentage of Participants With an HbA1c Target Value of ≤6.5% (48 mmol/Mol) | Week 40 | Percentage of Participants with an HbA1c target value of less than or equal to (≤) 6.5% (48 mmol/mol) was analysed by Logistic regression with analysis country, treatment by baseline and treatment by strata in the model. Strata were defined by joint levels of baseline HbA1c (≤8.0%, \>8.0%) and prior use of any antihyperglycemic medication (yes or no). |
| Change From Baseline in Fasting Serum Glucose (FSG) | Baseline, Week 40 | 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. |
| Percent Change From Baseline in Body Weight | Baseline, Week 40 | Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a 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 (≤8.0%, \>8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured. |
| Change From Baseline in Body Weight | Baseline, Week 40 | Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a 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 (≤8.0%, \>8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured. |
| Percent Change From Baseline in Non-High-Density Lipoprotein (Non-HDL) Cholesterol | Baseline, Week 40 | Values represented under "Geometric LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a MMRM with analysis : log (Actual Measurement/Baseline) = country, treatment by time, log(baseline) by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of baseline HbA1c (≤8.0%, \>8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured. |
| Percent Change From Baseline in Triglycerides | Baseline, Week 40 | Values represented under "Geometric LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a MMRM with analysis : log (Actual Measurement/Baseline) = country, treatment by time, log(baseline) by time by treatment, and strata by time by treatment in the model. Strata were defined by joint levels of baseline HbA1c (≤8.0%, \>8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured. |
| Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) | Baseline, Week 40 | The self-monitored plasma glucose (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. Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a 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 (≤8.0%, \>8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured. |
| Percentage of Participants With Greater Than or Equal to (≥) 5% Body Weight Reduction | Week 40 | Percentage of participants with ≥5% body weight reduction was analysed by Logistic regression with analysis country, treatment by baseline and treatment by strata in the model. Strata were defined by joint levels of baseline HbA1c (≤8.0%, \>8.0%) and prior use of any antihyperglycemic medication (yes or no). |
| Change From Baseline in Systolic Blood Pressure (SBP) | Baseline, Week 40 | Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a 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 (≤8.0%, \>8.0%) and prior use of any antihyperglycemic medication (yes or no). Variance-covariance structure for change from baseline was unstructured. |
| Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical-Component and Mental-Component) Scores | Baseline, Week 40 | 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
China, India, 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 | 53.3 years STANDARD_DEVIATION 12.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 223 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 335 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HemoglobinA1c (HbA1c) | 7.99 Percentage of HbA1c STANDARD_DEVIATION 0.89 |
| Race (NIH/OMB) American Indian or Alaska Native | 35 Participants |
| Race (NIH/OMB) Asian | 245 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 38 Participants |
| Region of Enrollment China | 51 Participants |
| Region of Enrollment India | 22 Participants |
| Region of Enrollment Japan | 26 Participants |
| Region of Enrollment Mexico | 40 Participants |
| Region of Enrollment United States | 42 Participants |
| Sex: Female, Male Female | 63 Participants |
| Sex: Female, Male Male | 69 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 / 138 | 2 / 143 | 1 / 137 | 0 / 141 |
| other Total, other adverse events | 110 / 138 | 118 / 143 | 118 / 137 | 123 / 141 |
| serious Total, serious adverse events | 5 / 138 | 8 / 143 | 7 / 137 | 4 / 141 |
Outcome results
None listed