Type 2 Diabetes
Conditions
Brief summary
The main purpose of this study is to investigate the efficacy and safety of Tirzepatide monotherapy in Chinese participants with Type 2 Diabetes.
Interventions
DRUGTirzepatide
Administered SC
DRUGPlacebo
Administered SC
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 * Are of stable weight 5%) during the 90 days preceding screening and agree not to initiate a diet and/or exercise program during the study with the intent of reducing body weight other than the lifestyle and dietary measures for diabetes treatment * Have Body Mass Index (BMI) ≥23.0 kilogram per square meter (kg/m²)
Exclusion criteria
* Have Type 1 Diabetes * Have a history of chronic or acute pancreatitis any time prior to study entry * Are currently receiving treatment for diabetic retinopathy and/or macular edema * Have a history of ketoacidosis or hyperosmolar state/coma * Have a history of New York Heart Association Functional Classification IV congestive heart failure (CHF) * Have acute or chronic hepatitis including a history of autoimmune hepatitis * Use of insulin 1-year preceding screening and between screening and baseline; use of any antihyperglycemic medication 90 days preceding screening and between screening and baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) | Baseline, Week 40 | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least squares (LS) mean was calculated using ANCOVA model with Baseline + Prior Antihyperglycemic Use + Treatment (Type III sum of squares) as variables. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Serum Glucose | Baseline, Week 40 | LS mean was calculated using ANCOVA model with Baseline + Prior Antihyperglycemic Use + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares) as variables. |
| Percentage of Participants With HbA1c Target Values of ≤6.5% (≤48 mmol/Mol) | Week 40 | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. Percentage of participants with HbA1c ≤6.5% (≤48 mmol/Mol) is reported here. |
| Change From Baseline in Body Weight | Baseline, Week 40 | LS mean was calculated using ANCOVA model with Baseline + Prior Antihyperglycemic Use + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares) as variables. |
| Percentage of Participants With HbA1c Target Values of <5.7% (<39 mmol/Mol) | Week 40 | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. Percentage of participants with HbA1c \<5.7% (\<39 mmol/mol) is reported here. |
| Percentage of Participants With HbA1c Target Values of <7.0% (<53 Millimole/Mole [mmol/Mol]) | Week 40 | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. Percentage of participants with HbA1c \<7.0% (\<53 mmol/mol) is reported here. |
| Percentage of Participants Who Achieved Weight Loss of ≥5% | Week 40 | Percentage of Participants who Achieved Weight Loss ≥5% is reported here. |
| Percentage of Participants Who Achieved Weight Loss of ≥10% | Week 40 | Percentage of Participants who Achieved Weight Loss ≥10% is reported here. |
| Percentage of Participants Who Achieved Weight Loss of ≥15% | Week 40 | Percentage of Participants who Achieved Weight Loss ≥15% is reported here. |
| Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose Profiles (SMBG) | Baseline, Week 40 | 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 calculated using mixed model repeated measures (MMRM) for post-baseline measures: Variable = Baseline + Baseline HbA1c (\<=8.5%, \>8.5%) + Prior Antihyperglycemic Use + Treatment + Time + Treatment\*Time(Type III sum of squares). Variance-Covariance structure (Change from Baseline) = Unstructured. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 5 mg Tirzepatide Participants received 5 mg of tirzepatide administered as SC injection via a SDP QW for 40 weeks.
The starting dose of tirzepatide was 2.5 mg QW, which increased by 2.5 mg every 4 weeks until the maintenance dose of 5 mg was reached | 52 |
| 10 mg Tirzepatide Participants received 10 mg of tirzepatide administered as SC injection via a SDP QW for 40 weeks.
The starting dose of tirzepatide was 2.5 mg QW, which increased by 2.5 mg every 4 weeks (2.5 mg to 5 mg to 7.5 mg to 10 mg) until the maintenance dose of 10 mg was reached. | 51 |
| 15 mg Tirzepatide Participants received 15 mg of tirzepatide administered as SC injection via a SDP QW for 40 weeks.
The starting dose of tirzepatide was 2.5 mg QW, which increased by 2.5 mg every 4 weeks (2.5 mg to 5 mg to 7.5 mg to 10 mg to 12.5 mg to 15 mg) until the maintenance dose of 15 mg was reached. | 52 |
| Placebo Participants received tirzepatide matched placebo administered as SC injection via a SDP QW for 40 weeks. | 51 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Pregnancy | 0 | 1 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 3 | 0 | 0 |
| Overall Study | Subject Required long-term Initiation of Rescue Antihyperglycemic Medication | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | 5 mg Tirzepatide | 10 mg Tirzepatide | 15 mg Tirzepatide | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 46.30 years STANDARD_DEVIATION 11.37 | 50.70 years STANDARD_DEVIATION 10.79 | 50.60 years STANDARD_DEVIATION 12.11 | 47.60 years STANDARD_DEVIATION 11.56 | 48.80 years STANDARD_DEVIATION 11.54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 51 Participants | 52 Participants | 51 Participants | 206 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Percentage of Hemoglobin A1c (HbA1c) at Baseline | 8.07 Percentage of HbA1c STANDARD_DEVIATION 0.77 | 8.13 Percentage of HbA1c STANDARD_DEVIATION 0.78 | 7.97 Percentage of HbA1c STANDARD_DEVIATION 0.81 | 7.92 Percentage of HbA1c STANDARD_DEVIATION 0.67 | 8.02 Percentage of HbA1c STANDARD_DEVIATION 0.76 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 52 Participants | 51 Participants | 52 Participants | 51 Participants | 206 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 52 participants | 51 participants | 52 participants | 51 participants | 206 participants |
| Sex: Female, Male Female | 23 Participants | 20 Participants | 25 Participants | 22 Participants | 90 Participants |
| Sex: Female, Male Male | 29 Participants | 31 Participants | 27 Participants | 29 Participants | 116 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 | 0 / 52 | 0 / 51 | 0 / 52 | 0 / 51 |
| other Total, other adverse events | 41 / 52 | 44 / 51 | 45 / 52 | 36 / 51 |
| serious Total, serious adverse events | 5 / 52 | 6 / 51 | 3 / 52 | 5 / 51 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c)
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least squares (LS) mean was calculated using ANCOVA model with Baseline + Prior Antihyperglycemic Use + Treatment (Type III sum of squares) as variables.
Time frame: Baseline, Week 40
Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline value at the specified time point for this outcome, regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) | -2.19 percentage of HbA1c | Standard Error 0.121 |
| 10 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.75 percentage of HbA1c | Standard Error 0.131 |
| 15 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) | -2.03 percentage of HbA1c | Standard Error 0.124 |
| Placebo | Change From Baseline in Hemoglobin A1c (HbA1c) | -0.77 percentage of HbA1c | Standard Error 0.126 |
p-value: <0.00195% CI: [-1.76, -1.07]ANCOVA
p-value: <0.00195% CI: [-1.34, -0.63]ANCOVA
p-value: <0.00195% CI: [-1.61, -0.92]ANCOVA
Secondary
Change From Baseline in Body Weight
LS mean was calculated using ANCOVA model with Baseline + Prior Antihyperglycemic Use + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares) as variables.
Time frame: Baseline, Week 40
Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline value at the specified time point for this outcome, regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Tirzepatide | Change From Baseline in Body Weight | -6.1 kilograms (kg) | Standard Error 0.68 |
| 10 mg Tirzepatide | Change From Baseline in Body Weight | -5.5 kilograms (kg) | Standard Error 0.71 |
| 15 mg Tirzepatide | Change From Baseline in Body Weight | -8.7 kilograms (kg) | Standard Error 0.69 |
| Placebo | Change From Baseline in Body Weight | -1.3 kilograms (kg) | Standard Error 0.7 |
p-value: <0.00195% CI: [-6.7, -2.9]ANCOVA
p-value: <0.00195% CI: [-6.2, -2.3]ANCOVA
p-value: <0.00195% CI: [-9.3, -5.4]ANCOVA
Secondary
Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose Profiles (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 calculated using mixed model repeated measures (MMRM) for post-baseline measures: Variable = Baseline + Baseline HbA1c (\<=8.5%, \>8.5%) + Prior Antihyperglycemic Use + Treatment + Time + Treatment\*Time(Type III sum of squares). Variance-Covariance structure (Change from Baseline) = Unstructured.
Time frame: Baseline, Week 40
Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline value at the specified time point for this outcome regardless of adherence to study drug or initiation of rescue antihyperglycemic medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Tirzepatide | Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose Profiles (SMBG) | -78.4 milligram per deciliter (mg/dL) | Standard Error 3.959 |
| 10 mg Tirzepatide | Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose Profiles (SMBG) | -78.3 milligram per deciliter (mg/dL) | Standard Error 4.185 |
| 15 mg Tirzepatide | Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose Profiles (SMBG) | -80.8 milligram per deciliter (mg/dL) | Standard Error 4.186 |
| Placebo | Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose Profiles (SMBG) | -33.9 milligram per deciliter (mg/dL) | Standard Error 5.223 |
p-value: <0.00195% CI: [-57.5, -31.5]Mixed Models Analysis
p-value: <0.00195% CI: [-57.6, -31.1]Mixed Models Analysis
p-value: <0.00195% CI: [-60.1, -33.7]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Serum Glucose
LS mean was calculated using ANCOVA model with Baseline + Prior Antihyperglycemic Use + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares) as variables.
Time frame: Baseline, Week 40
Population: All randomized participants who received at least one dose of study drug with baseline and post-baseline value at the specified time point for this outcome, regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Tirzepatide | Change From Baseline in Fasting Serum Glucose | -55.0 milligram per deciliter (mg/dL) | Standard Error 3 |
| 10 mg Tirzepatide | Change From Baseline in Fasting Serum Glucose | -54.8 milligram per deciliter (mg/dL) | Standard Error 3.16 |
| 15 mg Tirzepatide | Change From Baseline in Fasting Serum Glucose | -55.4 milligram per deciliter (mg/dL) | Standard Error 3.06 |
| Placebo | Change From Baseline in Fasting Serum Glucose | -30.2 milligram per deciliter (mg/dL) | Standard Error 3.07 |
p-value: <0.00195% CI: [-33.3, -16.3]ANCOVA
p-value: <0.00195% CI: [-33.2, -15.9]ANCOVA
p-value: <0.00195% CI: [-33.7, -16.7]ANCOVA
Secondary
Percentage of Participants Who Achieved Weight Loss of ≥10%
Percentage of Participants who Achieved Weight Loss ≥10% is reported here.
Time frame: Week 40
Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥10% | 27.45 percentage of participants |
| 10 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥10% | 33.33 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥10% | 58.14 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Weight Loss of ≥10% | 0 percentage of participants |
p-value: 0.01195% CI: [2.29, 664.36]Regression, Logistic
p-value: 0.00595% CI: [3.34, 949.59]Regression, Logistic
p-value: <0.00195% CI: [7.58, 2145.42]Regression, Logistic
Secondary
Percentage of Participants Who Achieved Weight Loss of ≥15%
Percentage of Participants who Achieved Weight Loss ≥15% is reported here.
Time frame: Week 40
Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥15% | 9.80 percentage of participants |
| 10 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥15% | 13.33 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥15% | 37.21 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Weight Loss of ≥15% | 0 percentage of participants |
p-value: 0.07795% CI: [0.75, 254.78]Regression, Logistic
p-value: 0.06295% CI: [0.87, 281.74]Regression, Logistic
p-value: 0.00495% CI: [3.9, 1140.13]Regression, Logistic
Secondary
Percentage of Participants Who Achieved Weight Loss of ≥5%
Percentage of Participants who Achieved Weight Loss ≥5% is reported here.
Time frame: Week 40
Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥5% | 54.90 percentage of participants |
| 10 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥5% | 66.67 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥5% | 88.37 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Weight Loss of ≥5% | 7.41 percentage of participants |
p-value: <0.00195% CI: [5.27, 62.73]Regression, Logistic
p-value: <0.00195% CI: [8.87, 108.05]Regression, Logistic
p-value: <0.00195% CI: [19.36, 278.4]Regression, Logistic
Secondary
Percentage of Participants With HbA1c Target Values of <5.7% (<39 mmol/Mol)
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. Percentage of participants with HbA1c \<5.7% (\<39 mmol/mol) is reported here.
Time frame: Week 40
Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg Tirzepatide | Percentage of Participants With HbA1c Target Values of <5.7% (<39 mmol/Mol) | 40.38 percentage of participants |
| 10 mg Tirzepatide | Percentage of Participants With HbA1c Target Values of <5.7% (<39 mmol/Mol) | 34.09 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c Target Values of <5.7% (<39 mmol/Mol) | 56.25 percentage of participants |
| Placebo | Percentage of Participants With HbA1c Target Values of <5.7% (<39 mmol/Mol) | 0 percentage of participants |
p-value: 0.00395% CI: [4.4, 1333.29]Regression, Logistic
p-value: <0.00195% CI: [2.8, 868.67]Regression, Logistic
p-value: <0.00195% CI: [6.8, 2055.04]Regression, Logistic
Secondary
Percentage of Participants With HbA1c Target Values of ≤6.5% (≤48 mmol/Mol)
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. Percentage of participants with HbA1c ≤6.5% (≤48 mmol/Mol) is reported here.
Time frame: Week 40
Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg Tirzepatide | Percentage of Participants With HbA1c Target Values of ≤6.5% (≤48 mmol/Mol) | 88.46 percentage of participants |
| 10 mg Tirzepatide | Percentage of Participants With HbA1c Target Values of ≤6.5% (≤48 mmol/Mol) | 75.00 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c Target Values of ≤6.5% (≤48 mmol/Mol) | 81.25 percentage of participants |
| Placebo | Percentage of Participants With HbA1c Target Values of ≤6.5% (≤48 mmol/Mol) | 23.40 percentage of participants |
p-value: <0.00195% CI: [8.7, 75.36]Regression, Logistic
p-value: <0.00195% CI: [2.88, 18.25]Regression, Logistic
p-value: <0.00195% CI: [4.23, 28.34]Regression, Logistic
Secondary
Percentage of Participants With HbA1c Target Values of <7.0% (<53 Millimole/Mole [mmol/Mol])
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. Percentage of participants with HbA1c \<7.0% (\<53 mmol/mol) is reported here.
Time frame: Week 40
Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg Tirzepatide | Percentage of Participants With HbA1c Target Values of <7.0% (<53 Millimole/Mole [mmol/Mol]) | 90.38 percentage of participants |
| 10 mg Tirzepatide | Percentage of Participants With HbA1c Target Values of <7.0% (<53 Millimole/Mole [mmol/Mol]) | 86.36 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c Target Values of <7.0% (<53 Millimole/Mole [mmol/Mol]) | 83.33 percentage of participants |
| Placebo | Percentage of Participants With HbA1c Target Values of <7.0% (<53 Millimole/Mole [mmol/Mol]) | 38.30 percentage of participants |
p-value: <0.00195% CI: [5.62, 51.73]Regression, Logistic
p-value: <0.00195% CI: [2.77, 20.37]Regression, Logistic
p-value: <0.00195% CI: [2.74, 19.14]Regression, Logistic