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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,698
Administered orally
Administered orally
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]
* 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%).
Time frame: Baseline, Week 52
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]
* 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%).
Time frame: Baseline, Week 52
Percentage of Participants Who Achieved HbA1c <7.0% [53 Millimoles/Mole (mmol/Mol)]
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 \[\<=8.0%, \>8.0%\]).
Time frame: Week 52
Percentage of Participants Who Achieved HbA1c <=6.5% (48 mmol/Mol)
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 \[\<=8.0%, \>8.0%\]).
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Absolute Clinical Research
Phoenix, Arizona, United States
San Fernando Valley Health Institute
Canoga Park, California, United States
Neighborhood Healthcare Institute of Health
Escondido, California, United States
Velocity Clinical Research, Gardena
Gardena, California, United States
Biopharma Informatic, LLC
Los Angeles, California, United States
Velocity Clinical Research, Westlake
Los Angeles, California, United States
Infinity Clinical Research - Norco
Norco, California, United States
Valley Clinical Trials, Inc.
Northridge, California, United States
Norcal Endocrinology & Internal Medicine
San Ramon, California, United States
Encompass Clinical Research
Spring Valley, California, United States
...and 121 more locations
Time frame: Week 52
Percentage of Participants Who Achieved HbA1c <5.7% (39 mmol/Mol)
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 \[\<=8.0%, \>8.0%\]).
Time frame: Week 52
Percent Change From Baseline in Body Weight
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%).
Time frame: Baseline, Week 52
Change From Baseline in Body Weight
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%).
Time frame: Baseline, Week 52
Change From Baseline in Fasting Serum Glucose
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%).
Time frame: Baseline, Week 52
Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose (SMBG)
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%).
Time frame: Baseline, Week 52
Percentage of Participants Who Achieved Weight Loss of >=5%
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 \[\<=8.0%, \>8.0%\]).
Time frame: Week 52
Percentage of Participants Who Achieved Weight Loss of >=10%
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 \[\<=8.0%, \>8.0%\]).
Time frame: Week 52
Percentage of Participants Who Achieved Weight Loss of >=15%
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 \[\<=8.0%, \>8.0%\]).
Time frame: Week 52
Change From Baseline in Systolic Blood Pressure (SBP)
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%).
Time frame: Baseline, Week 52
Change From Baseline in Diastolic Blood Pressure (DBP)
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%).
Time frame: Baseline, Week 52
Percent Change From Baseline in Total Serum Cholesterol
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%).
Time frame: Baseline, Week 52
Percent Change From Baseline in Serum Low Density Lipoprotein (LDL) Cholesterol
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%).
Time frame: Baseline, Week 52
Percent Change From Baseline in Serum Non High Density Lipoprotein (Non-HDL) Cholesterol
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%).
Time frame: Baseline, Week 52
Percent Change From Baseline in Serum Triglycerides
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%).
Time frame: Baseline, Week 52
Percent Change From Baseline in Serum High Density Lipoprotein (HDL) Cholesterol
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%).
Time frame: Baseline, Week 52
Percent Change From Baseline in Serum Very Low Density Lipoprotein (VLDL) Cholesterol
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%).
Time frame: Baseline, Week 52
Change From Baseline in Short Form 36 Version 2 (SF-36-v2) Acute Form (Physical Component and Mental Component Scores)
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.
Time frame: Baseline, Week 52