Type 2 Diabetes
Conditions
Keywords
glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), GIP/GLP-1 dual receptor agonist, T2DM
Brief summary
The purpose of this study is to compare the safety and efficacy of the study drug tirzepatide to placebo in participants with type 2 diabetes that are already on insulin glargine, with or without metformin. Participants will administer tirzepatide or placebo along with their previous glucose lowering medications. The study will last approximately 47 weeks and may include about 23 visits.
Interventions
DRUGTirzepatide
Administered SC as add-on to the pre-trial background medication.
DRUGPlacebo
Administered SC as add-on to the pre-trial background medication.
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 been diagnosed with type 2 diabetes mellitus (T2DM) and have been treated with insulin glargine (U100), once daily with or without metformin ≥3 months prior to screening visit. * Have HbA1c between ≥7.0% and ≤10.5%. * Have a stable weight (± 5%) for at least 3 months before screening. * Have a body mass index (BMI) ≥23 kilograms per meter squared (kg/m²) at screening.
Exclusion criteria
* Have type 1 diabetes mellitus. * Have had chronic or acute pancreatitis any time prior to study entry. * Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring acute treatment. * Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss. * Have an estimated glomerular filtration rate \<30 mL/minute/1.73 m² \[for participants on metformin, estimated glomerular filtration rate \<45 mL/min/1.73 m2 (or lower than the country-specific threshold for using the protocol-required dose of metformin per local label)\] * Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months. * Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2. * Have been taking weight loss drugs, including over-the-counter medications during the last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) | 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 determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Body Weight | Baseline, Week 40 | Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percentage of Participants Achieving an HbA1c Target Value of <7% | Week 40 | Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A.HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. |
| Change From Baseline in Fasting Serum Glucose | Baseline, Week 40 | Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. LS Mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. |
| Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Baseline, Week 40 | The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment (Type III sum of squares). |
| Change From Baseline in HbA1c (5 mg) | 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 determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percentage Change From Baseline in Daily Mean Insulin Glargine Dose | Baseline, Week 40 | LS mean was calculated using MMRM model with log (Baseline) + Baseline Metformin Use (Yes, No) + Pooled Country + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. |
| Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia | Baseline through Safety Follow-Up (Up to Week 44) | The hypoglycemia events were defined by participant reported events with blood glucose \<54mg/dL) (\<3.0 mmol/L\] or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Treatment, with log (exposure in days/365.25) as an offset variable. |
| Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide | Week 7, 15, 23 and 39 post dose | AUC is a combined measure obtained from Week 7, 15, 23 and 39 and a single averaged measure of AUC was reported. |
| Percentage of Participants Achieving an HbA1c Target Value of <5.7% | Week 40 | Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. |
| Percentage of Participants Who Achieved Weight Loss ≥5% | Week 40 | Percentage of Participants who Achieved Weight Loss ≥5%. |
Countries
Czechia, Germany, Japan, Poland, Puerto Rico, Slovakia, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 5 mg Tirzepatide 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. | 116 |
| 10 mg Tirzepatide 10 mg tirzepatide administered SC once a week. | 119 |
| 15 mg Tirzepatide 15 mg tirzepatide administered SC once a week. | 120 |
| Placebo Placebo administered SC once a week. | 120 |
| Total | 475 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 3 | 5 | 2 |
Baseline characteristics
| Characteristic | 15 mg Tirzepatide | 5 mg Tirzepatide | Placebo | Total | 10 mg Tirzepatide |
|---|---|---|---|---|---|
| Age, Continuous | 60.50 years STANDARD_DEVIATION 9.92 | 61.50 years STANDARD_DEVIATION 9.81 | 60.00 years STANDARD_DEVIATION 9.63 | 60.60 years STANDARD_DEVIATION 9.88 | 60.40 years STANDARD_DEVIATION 10.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 5 Participants | 22 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 94 Participants | 98 Participants | 380 Participants | 95 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 22 Participants | 18 Participants | 17 Participants | 73 Participants | 16 Participants |
| Hemoglobin A1c | 8.23 Percentage of HbA1c STANDARD_DEVIATION 0.86 | 8.30 Percentage of HbA1c STANDARD_DEVIATION 0.88 | 8.37 Percentage of HbA1c STANDARD_DEVIATION 0.84 | 8.31 Percentage of HbA1c STANDARD_DEVIATION 0.85 | 8.36 Percentage of HbA1c STANDARD_DEVIATION 0.83 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 20 Participants | 22 Participants | 85 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 0 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 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 | 94 Participants | 95 Participants | 97 Participants | 380 Participants | 94 Participants |
| Region of Enrollment Czechia | 23 Participants | 24 Participants | 23 Participants | 94 Participants | 24 Participants |
| Region of Enrollment Germany | 33 Participants | 32 Participants | 32 Participants | 129 Participants | 32 Participants |
| Region of Enrollment Japan | 20 Participants | 19 Participants | 22 Participants | 82 Participants | 21 Participants |
| Region of Enrollment Poland | 10 Participants | 8 Participants | 9 Participants | 36 Participants | 9 Participants |
| Region of Enrollment Puerto Rico | 1 Participants | 2 Participants | 3 Participants | 12 Participants | 6 Participants |
| Region of Enrollment Slovakia | 8 Participants | 8 Participants | 8 Participants | 31 Participants | 7 Participants |
| Region of Enrollment Spain | 15 Participants | 13 Participants | 14 Participants | 57 Participants | 15 Participants |
| Region of Enrollment United States | 10 Participants | 10 Participants | 9 Participants | 34 Participants | 5 Participants |
| Sex: Female, Male Female | 55 Participants | 55 Participants | 54 Participants | 211 Participants | 47 Participants |
| Sex: Female, Male Male | 65 Participants | 61 Participants | 66 Participants | 264 Participants | 72 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 / 116 | 0 / 119 | 0 / 120 | 0 / 120 |
| other Total, other adverse events | 52 / 116 | 60 / 119 | 67 / 120 | 58 / 120 |
| serious Total, serious adverse events | 9 / 116 | 13 / 119 | 9 / 120 | 10 / 120 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
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 determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 40
Population: All randomized participants from who received at least 1 dose study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) | -2.59 Percentage of HbA1c | Standard Error 0.081 |
| 15 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) | -2.59 Percentage of HbA1c | Standard Error 0.083 |
| Placebo | Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) | -0.93 Percentage of HbA1c | Standard Error 0.079 |
p-value: <0.00195% CI: [-1.88, -1.43]Mixed Models Analysis
p-value: <0.00195% CI: [-1.88, -1.43]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight
Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 40
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Change From Baseline in Body Weight | -6.2 Kilograms (kg) | Standard Error 0.58 |
| 15 mg Tirzepatide | Change From Baseline in Body Weight | -8.2 Kilograms (kg) | Standard Error 0.58 |
| Placebo | Change From Baseline in Body Weight | -10.9 Kilograms (kg) | Standard Error 0.59 |
| Placebo | Change From Baseline in Body Weight | 1.7 Kilograms (kg) | Standard Error 0.57 |
p-value: <0.00195% CI: [-9.4, -6.3]Mixed Models Analysis
p-value: <0.00195% CI: [-11.5, -8.3]Mixed Models Analysis
p-value: <0.00195% CI: [-14.2, -11]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Serum Glucose
Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. LS Mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.
Time frame: Baseline, Week 40
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Change From Baseline in Fasting Serum Glucose | -61.4 milligram per Deciliter (mg/dL) | Standard Error 2.55 |
| 15 mg Tirzepatide | Change From Baseline in Fasting Serum Glucose | -67.9 milligram per Deciliter (mg/dL) | Standard Error 2.55 |
| Placebo | Change From Baseline in Fasting Serum Glucose | -67.7 milligram per Deciliter (mg/dL) | Standard Error 2.64 |
| Placebo | Change From Baseline in Fasting Serum Glucose | -38.9 milligram per Deciliter (mg/dL) | Standard Error 2.49 |
p-value: <0.00195% CI: [-29.5, -15.4]Mixed Models Analysis
p-value: <0.00195% CI: [-36, -22]Mixed Models Analysis
p-value: <0.00195% CI: [-35.9, -21.6]Mixed Models Analysis
Secondary
Change From Baseline in HbA1c (5 mg)
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 determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 40
Population: All randomized participants who received at least one dose of 5 mg tirzepatide, placebo and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Change From Baseline in HbA1c (5 mg) | -2.23 Percentage of HbA1c | Standard Error 0.081 |
| 15 mg Tirzepatide | Change From Baseline in HbA1c (5 mg) | -0.93 Percentage of HbA1c | Standard Error 0.079 |
p-value: <0.00195% CI: [-1.52, -1.07]Mixed Models Analysis
Secondary
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment (Type III sum of squares).
Time frame: Baseline, Week 40
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | -67.1 mg/dL | Standard Error 2.05 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | -71.7 mg/dL | Standard Error 2.04 |
| Placebo | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | -73.7 mg/dL | Standard Error 2.1 |
| Placebo | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | -39.4 mg/dL | Standard Error 2.07 |
Secondary
Percentage Change From Baseline in Daily Mean Insulin Glargine Dose
LS mean was calculated using MMRM model with log (Baseline) + Baseline Metformin Use (Yes, No) + Pooled Country + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.
Time frame: Baseline, Week 40
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Percentage Change From Baseline in Daily Mean Insulin Glargine Dose | 13.0 International Units (IU) | Standard Error 7.34 |
| 15 mg Tirzepatide | Percentage Change From Baseline in Daily Mean Insulin Glargine Dose | 8.1 International Units (IU) | Standard Error 7.03 |
| Placebo | Percentage Change From Baseline in Daily Mean Insulin Glargine Dose | -11.4 International Units (IU) | Standard Error 5.85 |
| Placebo | Percentage Change From Baseline in Daily Mean Insulin Glargine Dose | 75.0 International Units (IU) | Standard Error 11.11 |
95% CI: [-46, -22.8]
95% CI: [-48.3, -26.1]
95% CI: [-57.7, -39.4]
Secondary
Percentage of Participants Achieving an HbA1c Target Value of <5.7%
Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Time frame: Week 40
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants Achieving an HbA1c Target Value of <5.7% | 26.09 Percentage of Participants |
| 15 mg Tirzepatide | Percentage of Participants Achieving an HbA1c Target Value of <5.7% | 47.79 Percentage of Participants |
| Placebo | Percentage of Participants Achieving an HbA1c Target Value of <5.7% | 62.39 Percentage of Participants |
| Placebo | Percentage of Participants Achieving an HbA1c Target Value of <5.7% | 2.54 Percentage of Participants |
p-value: <0.00195% CI: [3.93, 38]Regression, Logistic
p-value: <0.00195% CI: [10.52, 99.49]Regression, Logistic
p-value: <0.00195% CI: [18.27, 173.26]Regression, Logistic
Secondary
Percentage of Participants Achieving an HbA1c Target Value of <7%
Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A.HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Time frame: Week 40
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants Achieving an HbA1c Target Value of <7% | 93.04 Percentage of Participants |
| 15 mg Tirzepatide | Percentage of Participants Achieving an HbA1c Target Value of <7% | 97.35 Percentage of Participants |
| Placebo | Percentage of Participants Achieving an HbA1c Target Value of <7% | 94.02 Percentage of Participants |
| Placebo | Percentage of Participants Achieving an HbA1c Target Value of <7% | 33.90 Percentage of Participants |
p-value: <0.00195% CI: [15.23, 93.7]Regression, Logistic
p-value: <0.00195% CI: [30.02, 333.62]Regression, Logistic
p-value: <0.00195% CI: [16.92, 110.83]Regression, Logistic
Secondary
Percentage of Participants Who Achieved Weight Loss ≥5%
Percentage of Participants who Achieved Weight Loss ≥5%.
Time frame: Week 40
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value, excluding patients discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss ≥5% | 53.91 Percentage of Participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss ≥5% | 64.60 Percentage of Participants |
| Placebo | Percentage of Participants Who Achieved Weight Loss ≥5% | 84.62 Percentage of Participants |
| Placebo | Percentage of Participants Who Achieved Weight Loss ≥5% | 5.93 Percentage of Participants |
p-value: <0.00195% CI: [7.55, 38.93]Regression, Logistic
p-value: <0.00195% CI: [11.87, 62.55]Regression, Logistic
p-value: <0.00195% CI: [32.76, 193.44]Regression, Logistic
Secondary
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide
AUC is a combined measure obtained from Week 7, 15, 23 and 39 and a single averaged measure of AUC was reported.
Time frame: Week 7, 15, 23 and 39 post dose
Population: All randomized participants who received at least one dose and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide | 79700 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 24.5 |
| 15 mg Tirzepatide | Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide | 164000 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 26.7 |
| Placebo | Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide | 246000 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 26.4 |
Secondary
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia
The hypoglycemia events were defined by participant reported events with blood glucose \<54mg/dL) (\<3.0 mmol/L\] or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Treatment, with log (exposure in days/365.25) as an offset variable.
Time frame: Baseline through Safety Follow-Up (Up to Week 44)
Population: All randomly assigned participants who took at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia | 0.49 Episodes/participant/365.25 days | Standard Error 0.141 |
| 15 mg Tirzepatide | Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia | 0.66 Episodes/participant/365.25 days | Standard Error 0.169 |
| Placebo | Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia | 0.38 Episodes/participant/365.25 days | Standard Error 0.099 |
| Placebo | Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia | 0.51 Episodes/participant/365.25 days | Standard Error 0.149 |