Obesity, Overweight, Type 2 Diabetes
Conditions
Brief summary
This study will investigate the safety and efficacy of once daily oral treatment with orforglipron compared with placebo on body weight in adult participants with obesity or overweight and type 2 diabetes. The study will last about 77 weeks and may include up to 22 visits.
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 a body mass index (BMI) ≥27.0 kilogram/square meter (kg/m²). * Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight. * Have a diagnosis of Type 2 Diabetes (T2D), with HbA1c ≥7% (≥53 mmol/mol) to ≤10% (86 mmol/mol) and are on stable treatment for T2D for at least 90 days prior to screening, consisting of: * either diet/exercise alone or * up to 3 oral antihyperglycemic medications (excluding dipeptidyl peptidase IV inhibitors (DPP-4i) or glucagon-like peptide-1 (GLP-1) receptor agonists (RA).
Exclusion criteria
* Have Type 1 Diabetes (T1D), history of ketoacidosis or hyperosmolar state/coma, or any other types of diabetes except T2D. * Have a self-reported change in body weight \>5 kg (11 pounds) within 90 days prior to screening. * 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 family (first-degree relative) or personal history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia 2 (MEN2) syndrome. * Have had a history of chronic or acute pancreatitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight | Baseline, Week 72 | 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) for post-baseline measures with region + Baseline\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral antihyperglycemic medications (AHMs) classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved With Greater Than or Equal to (≥) 5% Body Weight Reduction From Baseline | Baseline to Week 72 | Percentage of participants with ≥5% body weight reduction was analysed by Logistic regression with the following variables: region + Baseline\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). |
| Percentage of Participants Who Achieved ≥10% Body Weight Reduction From Baseline | Baseline to Week 72 | Percentage of participants with ≥10% body weight reduction was analysed by Logistic regression with the following variables: region + Baseline\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). |
| Percentage of Participants Who Achieved ≥15% Body Weight Reduction From Baseline | Baseline to Week 72 | Percentage of participants with ≥15% body weight reduction was analysed by Logistic regression with the following variables: region + Baseline\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). |
| Change From Baseline in Waist Circumference | Baseline, Week 72 | 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) for post-baseline measures with region + Baseline\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured. |
| Change From Baseline in Hemoglobin A1c (HbA1c) % | Baseline, Week 72 | * 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) for post-baseline measures with region + Baseline\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured. |
| Change From Baseline in Fasting Serum Glucose (FSG) | Baseline, Week 72 | 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) for post-baseline measures with region + Baseline\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured. |
| Percentage of Participants Who Achieved Hemoglobin A1c (HbA1c) Target Value (<6.5%) | Baseline to Week 72 | Percentage of participants who achieved hemoglobin A1c (HbA1c\<6.5%) was analysed by Logistic regression with the following variables: region + Baseline\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). |
| Percentage of Participants Who Achieved Hemoglobin A1c (HbA1c) Target Value (<7.0%) | Baseline to Week 72 | Percentage of participants who achieved hemoglobin A1c (HbA1c\<7%) was analysed by Logistic regression with the following variables: region + Baseline\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). |
| Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg) | Baseline, Week 72 | 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) for post-baseline measures with region + Baseline\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured. |
| Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg) | Baseline, Week 72 | 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) for post-baseline measures with region + Baseline\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured. |
| Percent Change From Baseline in Fasting Insulin | Baseline, Week 72 | * Fasting Insulin is a test used to measure the amount of insulin in the body. * Values represented under "Geometric Least Squares Mean" are model-based estimates (MBE) of the unconditional average treatment effect. For post-baseline measures, MBE was calculated using a mixed-model repeated measures (MMRM) on log-transformed values, defined as log (Actual Measurement/Baseline) + Region + log (Baseline)\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). The variance-covariance structure was unstructured. |
| Percent Change From Baseline in Non-High-Density Lipoprotein (Non-HDL) Cholesterol (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg) | Baseline, Week 72 | Values represented under "Geometric Least Squares Mean" are model-based estimates (MBE) of the unconditional average treatment effect. For post-baseline measures, MBE was calculated using a mixed-model repeated measures (MMRM) on log-transformed values, defined as log (Actual Measurement/Baseline) + Region + log (Baseline)\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). The variance-covariance structure was unstructured. |
| Percent Change From Baseline in Triglycerides (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg) | Baseline, Week 72 | Values represented under "Geometric Least Square Mean" are model-based estimates (MBE) of the unconditional average treatment effect. For post-baseline measures, MBE was calculated using a mixed-model repeated measures (MMRM) on log-transformed values, defined on log-transformed values, defined as log (Actual Measurement/Baseline) + Region + log (Baseline)\*Time\*Treatment + Strata\*Time\*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). The variance-covariance structure was unstructured. |
| Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical-Component and Mental-Component) Scores (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg) | Baseline, Week 72 | The SF-36v2 acute form, (1-week recall version) assesses participants' health-related quality of life on 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, Australia, Brazil, China, Czechia, Germany, Greece, India, Puerto Rico, South Korea, 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 | 56.8 years STANDARD_DEVIATION 10.4 |
| Baseline Weight | 101.19 kilogram (kg) STANDARD_DEVIATION 22.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 97 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 221 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 279 Participants |
| Race (NIH/OMB) Black or African American | 28 Participants |
| Race (NIH/OMB) More than one race | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 30 Participants |
| Race (NIH/OMB) White | 235 Participants |
| Region of Enrollment Argentina | 149 Participants |
| Region of Enrollment Australia | 18 Participants |
| Region of Enrollment Brazil | 48 Participants |
| Region of Enrollment China | 113 Participants |
| Region of Enrollment Czechia | 194 Participants |
| Region of Enrollment Germany | 34 Participants |
| Region of Enrollment Greece | 15 Participants |
| Region of Enrollment India | 89 Participants |
| Region of Enrollment South Korea | 9 Participants |
| Region of Enrollment United States | 442 Participants |
| Sex: Female, Male Female | 155 Participants |
| Sex: Female, Male Male | 177 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 | 4 / 628 | 0 / 328 | 4 / 331 | 2 / 321 |
| other Total, other adverse events | 452 / 628 | 231 / 328 | 262 / 331 | 255 / 321 |
| serious Total, serious adverse events | 55 / 628 | 24 / 328 | 34 / 331 | 35 / 321 |
Outcome results
None listed