Type 2 Diabetes Mellitus
Conditions
Keywords
glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), GIP/GLP-1 dual receptor agonist, T2DM
Brief summary
The goal for this study is to evaluate the efficacy and safety of tirzepatide versus placebo in participants with type 2 diabetes not under control with diet and exercise alone. The study will last approximately 47 weeks and may include about 15 visits.
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 been diagnosed with type 2 diabetes mellitus (T2DM). * Are naïve to diabetes injectable therapies and have not used any oral antihyperglycemic medications (OAMs) during the 3 months preceding screening. * Have HbA1c between ≥7.0% and ≤9.5%. * Be of stable weight (± 5%) for at least 3 months before screening. * Have a 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. * 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) | 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 + Pooled Country + Prior Use of oral antihyperglycemic medication (OAM) (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With 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. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percentage of Participants With 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. |
| Change From Baseline in Body Weight | Baseline, Week 40 | Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percentage of Participants Who Achieved Weight Loss ≥5% | Week 40 | Percentage of Participants who Achieved Weight Loss ≥5%. |
| Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia | Baseline through end of 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 HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + 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 and 23 | Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide. AUC is a combined measure obtained from Week 7, 15 and 23, and a single averaged measure of AUC was reported. |
| 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 + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares). |
Countries
India, Japan, Mexico, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 5 mg Tirzepatide Participants received 5 mg of tirzepatide as subcutaneous injection once a week. | 121 |
| 10 mg Tirzepatide Participants received 10mg of tirzepatide as subcutaneous injection once a week. | 121 |
| 15 mg Tirzepatide Participants received 15mg of tirzepatide as subcutaneous injection once a week. | 121 |
| Placebo Participants received placebo as subcutaneous injection once a week. | 115 |
| Total | 478 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 1 | 1 |
| Overall Study | Death | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 2 | 3 | 5 |
| Overall Study | Participant left the country | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 13 | 6 |
Baseline characteristics
| Characteristic | Total | Placebo | 15 mg Tirzepatide | 10 mg Tirzepatide | 5 mg Tirzepatide |
|---|---|---|---|---|---|
| Age, Continuous | 54.10 years STANDARD_DEVIATION 11.88 | 53.60 years STANDARD_DEVIATION 12.79 | 52.90 years STANDARD_DEVIATION 12.34 | 55.80 years STANDARD_DEVIATION 10.35 | 54.10 years STANDARD_DEVIATION 11.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 207 Participants | 48 Participants | 55 Participants | 54 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 184 Participants | 45 Participants | 42 Participants | 49 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 87 Participants | 22 Participants | 24 Participants | 18 Participants | 23 Participants |
| Hemoglobin A1c | 7.94 Percentage of HbA1c STANDARD_DEVIATION 0.87 | 8.05 Percentage of HbA1c STANDARD_DEVIATION 0.8 | 7.85 Percentage of HbA1c STANDARD_DEVIATION 1.02 | 7.90 Percentage of HbA1c STANDARD_DEVIATION 0.78 | 7.97 Percentage of HbA1c STANDARD_DEVIATION 0.841 |
| Race (NIH/OMB) American Indian or Alaska Native | 118 Participants | 26 Participants | 30 Participants | 31 Participants | 31 Participants |
| Race (NIH/OMB) Asian | 168 Participants | 38 Participants | 42 Participants | 43 Participants | 45 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 5 Participants | 6 Participants | 4 Participants | 7 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 | 170 Participants | 46 Participants | 43 Participants | 43 Participants | 38 Participants |
| Region of Enrollment India | 73 Participants | 17 Participants | 18 Participants | 20 Participants | 18 Participants |
| Region of Enrollment Japan | 89 Participants | 21 Participants | 23 Participants | 22 Participants | 23 Participants |
| Region of Enrollment Mexico | 164 Participants | 40 Participants | 42 Participants | 40 Participants | 42 Participants |
| Region of Enrollment Puerto Rico | 12 Participants | 1 Participants | 5 Participants | 4 Participants | 2 Participants |
| Region of Enrollment United States | 140 Participants | 36 Participants | 33 Participants | 35 Participants | 36 Participants |
| Sex: Female, Male Female | 231 Participants | 59 Participants | 58 Participants | 49 Participants | 65 Participants |
| Sex: Female, Male Male | 247 Participants | 56 Participants | 63 Participants | 72 Participants | 56 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 / 121 | 0 / 121 | 0 / 121 | 1 / 115 |
| other Total, other adverse events | 50 / 121 | 55 / 121 | 53 / 121 | 54 / 115 |
| serious Total, serious adverse events | 5 / 121 | 2 / 121 | 1 / 121 | 3 / 115 |
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 determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Prior Use of oral antihyperglycemic medication (OAM) (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 40
Population: All randomized participants who received 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 |
|---|---|---|---|
| 5 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.87 Percentage of HbA1c | Standard Error 0.094 |
| 10 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.89 Percentage of HbA1c | Standard Error 0.096 |
| 15 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) | -2.07 Percentage of HbA1c | Standard Error 0.098 |
| Placebo | Change From Baseline in Hemoglobin A1c (HbA1c) | 0.04 Percentage of HbA1c | Standard Error 0.105 |
p-value: <0.00195% CI: [-2.18, -1.63]Mixed Models Analysis
p-value: <0.00195% CI: [-2.21, -1.65]Mixed Models Analysis
p-value: <0.00195% CI: [-2.39, -1.83]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 + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 40
Population: All randomized participants who received 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 |
|---|---|---|---|
| 5 mg Tirzepatide | Change From Baseline in Body Weight | -7.0 Kilograms (kg) | Standard Error 0.52 |
| 10 mg Tirzepatide | Change From Baseline in Body Weight | -7.8 Kilograms (kg) | Standard Error 0.53 |
| 15 mg Tirzepatide | Change From Baseline in Body Weight | -9.5 Kilograms (kg) | Standard Error 0.54 |
| Placebo | Change From Baseline in Body Weight | -0.7 Kilograms (kg) | Standard Error 0.57 |
p-value: <0.00195% CI: [-7.8, -4.7]Mixed Models Analysis
p-value: <0.00195% CI: [-8.6, -5.5]Mixed Models Analysis
p-value: <0.00195% CI: [-10.3, -7.2]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. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 40
Population: All randomized participants who received 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 |
|---|---|---|---|
| 5 mg Tirzepatide | Change From Baseline in Fasting Serum Glucose | -43.6 milligram per Deciliter (mg/dL) | Standard Error 3.4 |
| 10 mg Tirzepatide | Change From Baseline in Fasting Serum Glucose | -45.9 milligram per Deciliter (mg/dL) | Standard Error 3.45 |
| 15 mg Tirzepatide | Change From Baseline in Fasting Serum Glucose | -49.3 milligram per Deciliter (mg/dL) | Standard Error 3.62 |
| Placebo | Change From Baseline in Fasting Serum Glucose | 12.9 milligram per Deciliter (mg/dL) | Standard Error 4 |
p-value: 0.77695% CI: [-11.9, 8.9]Mixed Models Analysis
p-value: 0.62295% CI: [-13, 7.8]Mixed Models Analysis
p-value: 0.90895% CI: [-11.1, 9.8]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 + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 40
Population: All randomized participants who received 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 | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Morning Premeal - Fasting | -46.9 mg/dL | Standard Error 2.09 |
| 5 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Evening 2-hour Postmeal | -61.9 mg/dL | Standard Error 3.76 |
| 5 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Evening Premeal | -44.8 mg/dL | Standard Error 2.8 |
| 5 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Morning 2-hour Postmeal | -69.5 mg/dL | Standard Error 3.41 |
| 5 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Bedtime | -57.0 mg/dL | Standard Error 3.49 |
| 5 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Midday Premeal | -43.5 mg/dL | Standard Error 2.8 |
| 5 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Midday 2-hour Postmeal | -64.2 mg/dL | Standard Error 3.6 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Evening 2-hour Postmeal | -62.8 mg/dL | Standard Error 3.81 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Midday 2-hour Postmeal | -60.0 mg/dL | Standard Error 3.63 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Midday Premeal | -42.5 mg/dL | Standard Error 2.82 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Evening Premeal | -45.1 mg/dL | Standard Error 2.82 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Bedtime | -59.8 mg/dL | Standard Error 3.52 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Morning 2-hour Postmeal | -61.4 mg/dL | Standard Error 3.44 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Morning Premeal - Fasting | -47.9 mg/dL | Standard Error 2.11 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Midday 2-hour Postmeal | -63.4 mg/dL | Standard Error 3.84 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Morning Premeal - Fasting | -45.7 mg/dL | Standard Error 2.23 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Morning 2-hour Postmeal | -68.9 mg/dL | Standard Error 3.66 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Midday Premeal | -42.7 mg/dL | Standard Error 3 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Evening Premeal | -42.3 mg/dL | Standard Error 3.02 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Evening 2-hour Postmeal | -63.5 mg/dL | Standard Error 4.03 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Bedtime | -60.8 mg/dL | Standard Error 3.66 |
| Placebo | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Midday Premeal | -2.6 mg/dL | Standard Error 3.42 |
| Placebo | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Bedtime | -9.1 mg/dL | Standard Error 4.1 |
| Placebo | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Evening 2-hour Postmeal | -10.3 mg/dL | Standard Error 4.52 |
| Placebo | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Morning 2-hour Postmeal | -11.6 mg/dL | Standard Error 4.12 |
| Placebo | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Morning Premeal - Fasting | -9.2 mg/dL | Standard Error 2.53 |
| Placebo | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Evening Premeal | -5.8 mg/dL | Standard Error 3.38 |
| Placebo | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Midday 2-hour Postmeal | -12.7 mg/dL | Standard Error 4.33 |
Comparison: Morning Premeal - Fastingp-value: <0.00195% CI: [-44.1, -31.2]Mixed Models Analysis
Comparison: Morning Premeal - Fastingp-value: <0.00195% CI: [-45.1, -32.2]Mixed Models Analysis
Comparison: Morning Premeal - Fastingp-value: <0.00195% CI: [-43.1, -29.8]Mixed Models Analysis
Comparison: Morning 2-hour Postmealp-value: <0.00195% CI: [-68.4, -47.4]Mixed Models Analysis
Comparison: Morning 2-hour Postmealp-value: <0.00195% CI: [-60.3, -39.2]Mixed Models Analysis
Comparison: Morning 2-hour Postmealp-value: <0.00195% CI: [-68.1, -46.4]Mixed Models Analysis
Comparison: Midday Premealp-value: <0.00195% CI: [-49.6, -32.2]Mixed Models Analysis
Comparison: Midday Premealp-value: <0.00195% CI: [-48.6, -31.2]Mixed Models Analysis
Comparison: Midday Premealp-value: <0.00195% CI: [-49, -31.1]Mixed Models Analysis
Comparison: Midday 2-hour Postmealp-value: <0.00195% CI: [-62.5, -40.4]Mixed Models Analysis
Comparison: Midday 2-hour Postmealp-value: <0.00195% CI: [-58.4, -36.2]Mixed Models Analysis
Comparison: Midday 2-hour Postmealp-value: <0.00195% CI: [-62.1, -39.3]Mixed Models Analysis
Comparison: Evening Premealp-value: <0.00195% CI: [-47.6, -30.4]Mixed Models Analysis
Comparison: Evening Premealp-value: <0.00195% CI: [-47.9, -30.6]Mixed Models Analysis
Comparison: Evening Premealp-value: <0.00195% CI: [-45.3, -27.5]Mixed Models Analysis
Comparison: Evening 2-hour Postmealp-value: <0.00195% CI: [-63.2, -40.1]Mixed Models Analysis
Comparison: Evening 2-hour Postmealp-value: <0.00195% CI: [-64.1, -40.9]Mixed Models Analysis
Comparison: Evening 2-hour Postmealp-value: <0.00195% CI: [-65.1, -41.3]Mixed Models Analysis
Comparison: Bedtimep-value: <0.00195% CI: [-58.6, -37.4]Mixed Models Analysis
Comparison: Bedtimep-value: <0.00195% CI: [-61.3, -40.1]Mixed Models Analysis
p-value: <0.00195% CI: [-62.6, -40.9]Mixed Models Analysis
Secondary
Percentage of Participants Who Achieved Weight Loss ≥5%
Percentage of Participants who Achieved Weight Loss ≥5%.
Time frame: Week 40
Population: All randomized participants who received 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) |
|---|---|---|
| 5 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss ≥5% | 66.94 Percentage of participants |
| 10 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss ≥5% | 77.97 Percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss ≥5% | 76.72 Percentage of participants |
| Placebo | Percentage of Participants Who Achieved Weight Loss ≥5% | 14.29 Percentage of participants |
p-value: <0.00195% CI: [6.43, 23.94]Regression, Logistic
p-value: <0.00195% CI: [10.59, 42.18]Regression, Logistic
p-value: <0.00195% CI: [10.09, 40.04]Regression, Logistic
Secondary
Percentage of Participants With 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 randomized participants who received 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) |
|---|---|---|
| 5 mg Tirzepatide | Percentage of Participants With HbA1c Target Value of <5.7% | 33.88 Percentage of participants |
| 10 mg Tirzepatide | Percentage of Participants With HbA1c Target Value of <5.7% | 30.51 Percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c Target Value of <5.7% | 51.72 Percentage of participants |
| Placebo | Percentage of Participants With HbA1c Target Value of <5.7% | 0.89 Percentage of participants |
p-value: <0.00195% CI: [7.74, 209.71]Regression, Logistic
p-value: <0.00195% CI: [6.53, 178.19]Regression, Logistic
p-value: <0.00195% CI: [16.36, 443.13]Regression, Logistic
Secondary
Percentage of Participants With 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 randomized participants who received 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) |
|---|---|---|
| 5 mg Tirzepatide | Percentage of Participants With HbA1c Target Value of <7% | 86.78 Percentage of participants |
| 10 mg Tirzepatide | Percentage of Participants With HbA1c Target Value of <7% | 91.53 Percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c Target Value of <7% | 87.93 Percentage of participants |
| Placebo | Percentage of Participants With HbA1c Target Value of <7% | 19.64 Percentage of participants |
p-value: <0.00195% CI: [21.12, 113.67]Regression, Logistic
p-value: <0.00195% CI: [31.8, 203.19]Regression, Logistic
p-value: <0.00195% CI: [22.3, 125.73]Regression, Logistic
Secondary
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide. AUC is a combined measure obtained from Week 7, 15 and 23, and a single averaged measure of AUC was reported.
Time frame: Week 7, 15 and 23
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Tirzepatide | Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide | 86900 nanograms*hours per milliliter (h*ng/mL) | Geometric Coefficient of Variation 25.4 |
| 10 mg Tirzepatide | Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide | 171000 nanograms*hours per milliliter (h*ng/mL) | Geometric Coefficient of Variation 26.2 |
| 15 mg Tirzepatide | Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide | 252000 nanograms*hours per milliliter (h*ng/mL) | Geometric Coefficient of Variation 23.3 |
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 HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment, with log (exposure in days/365.25) as an offset variable.
Time frame: Baseline through end of safety follow-up (up to week 44)
Population: All randomized participants who received at least 1 dose of study drug and had a baseline and at least 1 post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg Tirzepatide | Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia | 0.02 Episodes/participant/365.25 days | Standard Error 0.002 |
| 10 mg Tirzepatide | Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia | 0.02 Episodes/participant/365.25 days | Standard Error 0.002 |
| 15 mg Tirzepatide | Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia | 0.02 Episodes/participant/365.25 days | Standard Error 0.002 |
| Placebo | Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia | 0.04 Episodes/participant/365.25 days | Standard Error 0.028 |