Diabetes Mellitus, Diabetes Type 2, Endocrine System Diseases, Glucose Metabolism Disorders, Metabolic Disease
Conditions
Brief summary
The main purpose of this study is to compare the effect of the addition of tirzepatide or placebo to titrated basal insulin on glycemic control 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
Yes
Inclusion criteria
* Have type 2 diabetes mellitus (T2DM) * Have HbA1c ≥7.0% (53 mmol/mol) to ≤11% (97 mmol/mol) * Have been treated with insulin glargine (U100) once daily alone, or in combination with metformin with or without SGLT-2i ≥90 days * Have a body mass index (BMI) ≥23 kilograms per meter squared (kg/m²)
Exclusion criteria
* Have type 1 diabetes mellitus (T1DM) * Have a history of chronic or acute pancreatitis * Have proliferative diabetic retinopathy or diabetic macular edema or nonproliferative diabetic retinopathy that requires acute treatment * Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2 * Have a history of severe hypoglycemia and/or hypoglycemia unawareness within the 6 months * Have a history of diabetic ketoacidosis or hyperosmolar state/coma within the 6 months * Have acute myocardial infarction, or cerebrovascular accident (stroke) or hospitalization due to congestive heart failure (CHF) in the past 2 months * Have a serum calcitonin level of ≥35 ng/L, as determined by central laboratory * Have acute or chronic hepatitis, signs, and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level \>3.0 times the upper limit of normal (ULN), as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial only if their ALT level is ≤3.0 times ULN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in HbA1c (Tirzepatide 10 or 15 Milligram [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 calculated using mixed model repeated measures (MMRM) for post-baseline measures: Variable = Baseline + SGLT2i Use (Yes/No) + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Body Weight | Baseline, Week 40 | LSMean was calculated using MMRM for post-baseline measures: Variable = Baseline + Baseline HbA1c (\<=8.0%, \>8.0%) + SGLT2i Use (Yes/No) + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured |
| Percentage of Participants With HbA1c <7.0% (53 Millimole/Mole [mmol/Mol]) and ≤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 \<7.0% (53 millimole/mole \[mmol/mol\]) and ≤6.5% (48 mmol/mol) is reported here. |
| Mean Change From Baseline in Fasting Serum Glucose | Baseline, Week 40 | LSMean was calculated using MMRM for post-baseline measures: Variable = Baseline + Baseline HbA1c (\<=8.0%, \>8.0%) + SGLT2i Use (Yes/No) + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured |
| Percentage of Participants With HbA1c <5.7% (39 mmol/Mol) [Tirzepatide 10 mg or 15 mg] | Week 40 | 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 with HbA1c \<5.7% (39 mmol/Mol) is reported here. |
| Percentage of Participants With HbA1c <5.7% (39 mmol/Mol) [Tirzepatide 5 mg] | Week 40 | 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 with HbA1c \<5.7% (39 mmol/Mol) is reported here. |
| Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | 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 MMRM for post-baseline measures: Variable = Baseline + Baseline HbA1c (\<=8.0%, \>8.0%) + SGLT2i Use (Yes/No) + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured. |
| Percentage of Participants Who Achieved Weight Loss of ≥5% | Week 40 | Percentage of Participants who Achieved Weight Loss ≥5% is reported here. |
| Mean Change From Baseline in HbA1c (Tirzepatide 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. LS mean was calculated using MMRM for post-baseline measures: Variable = Baseline + SGLT2i Use (Yes/No) + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured |
| Percentage of Participants Who Achieved Weight Loss of ≥15% | Week 40 | Percentage of Participants who Achieved Weight Loss ≥15% is reported here. |
| Percent Change From Baseline in Daily Mean Insulin Glargine Dose | Baseline, Week 40 | LS Mean was calculated using MMRM for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Baseline HbA1c (\<=8.0%, \>8.0%) + SGLT2i Use (Yes/No) + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Change from Baseline) = Unstructured. |
| Percentage of Participants With HbA1c <7.0%, Without Weight Gain (<0.1 Kilogram [kg]) and Without Hypoglycemia, (Blood Glucose <3.0 mmol/L <54 Milligram/Deciliter [mg/dL]) | Week 40 | Percentage of Participants with HbA1c \<7.0%, Without Weight Gain (\<0.1 Kilogram \[kg\]) and Without Hypoglycemia, (Blood Glucose \<3.0 mmol/L \<54 Milligram/Deciliter \[mg/dL\]) is reported here |
| Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.0 mmol/L [54 mg/dL]) | Week 40 | Percentage of Participants with HbA1c ≤6.5%, Without Weight Gain \<0.1 kg and Without Hypoglycemia (Blood glucose \<3.0 mmol/L \[54 mg/dL\]) is reported here. |
| Percentage of Participants With HbA1c <7.0%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia) | Week 40 | Percentage of Participants with HbA1c \<7.0%, Without Weight Gain \<0.1 kg and Without Hypoglycemia (Blood Glucose \<3.9 mmol/L \[70 mg/dL\] or Severe Hypoglycemia) is reported here. |
| Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia) | Week 40 | Percentage of Participants with HbA1c ≤6.5%, Without Weight Gain \<0.1 kg and Without Hypoglycemia (Blood glucose \<3.9 mmol/L \[70 mg/dL\] or Severe Hypoglycemia) 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. |
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. | 65 |
| 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. | 65 |
| 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. | 63 |
| Placebo Participants received tirzepatide matched placebo administered as SC injection via a SDP QW for 40 weeks. | 64 |
| Total | 257 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 2 | 1 |
| Overall Study | Assigned Treatment by Mistake | 1 | 0 | 0 | 1 |
| Overall Study | Death | 1 | 0 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 3 | 1 |
Baseline characteristics
| Characteristic | 5 mg Tirzepatide | 10 mg Tirzepatide | 15 mg Tirzepatide | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 58.10 years STANDARD_DEVIATION 9.97 | 55.00 years STANDARD_DEVIATION 11.58 | 55.80 years STANDARD_DEVIATION 10.11 | 58.00 years STANDARD_DEVIATION 10.24 | 56.70 years STANDARD_DEVIATION 10.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 65 Participants | 63 Participants | 64 Participants | 257 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 | 8.64 Percentage of HbA1c STANDARD_DEVIATION 0.95 | 8.60 Percentage of HbA1c STANDARD_DEVIATION 1.09 | 8.75 Percentage of HbA1c STANDARD_DEVIATION 0.99 | 8.84 Percentage of HbA1c STANDARD_DEVIATION 0.99 | 8.71 Percentage of HbA1c STANDARD_DEVIATION 1.01 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 65 Participants | 65 Participants | 63 Participants | 64 Participants | 257 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 | 65 Participants | 65 Participants | 63 Participants | 64 Participants | 257 Participants |
| Sex: Female, Male Female | 23 Participants | 25 Participants | 26 Participants | 25 Participants | 99 Participants |
| Sex: Female, Male Male | 42 Participants | 40 Participants | 37 Participants | 39 Participants | 158 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 | 1 / 65 | 0 / 65 | 0 / 63 | 0 / 64 |
| other Total, other adverse events | 45 / 65 | 49 / 65 | 49 / 63 | 31 / 64 |
| serious Total, serious adverse events | 8 / 65 | 5 / 65 | 8 / 63 | 7 / 64 |
Outcome results
Primary
Mean Change From Baseline in HbA1c (Tirzepatide 10 or 15 Milligram [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 calculated using mixed model repeated measures (MMRM) for post-baseline measures: Variable = Baseline + SGLT2i Use (Yes/No) + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. 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 excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Mean Change From Baseline in HbA1c (Tirzepatide 10 or 15 Milligram [mg]) | -26.1 millimoles per mole (mmol/mol) | Standard Error 1.367 |
| 15 mg Tirzepatide | Mean Change From Baseline in HbA1c (Tirzepatide 10 or 15 Milligram [mg]) | -25.9 millimoles per mole (mmol/mol) | Standard Error 1.386 |
| Placebo | Mean Change From Baseline in HbA1c (Tirzepatide 10 or 15 Milligram [mg]) | -9.96 millimoles per mole (mmol/mol) | Standard Error 1.34 |
p-value: <0.00195% CI: [-19.9, -12.36]Mixed Models Analysis
p-value: <0.00195% CI: [-19.7, -12.1]Mixed Models Analysis
Secondary
Mean Change From Baseline in Body Weight
LSMean was calculated using MMRM for post-baseline measures: Variable = Baseline + Baseline HbA1c (\<=8.0%, \>8.0%) + SGLT2i Use (Yes/No) + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. 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 excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Mean Change From Baseline in Body Weight | -2.7 kilograms (kg) | Standard Error 0.52 |
| 15 mg Tirzepatide | Mean Change From Baseline in Body Weight | -4.8 kilograms (kg) | Standard Error 0.54 |
| Placebo | Mean Change From Baseline in Body Weight | -4.3 kilograms (kg) | Standard Error 0.55 |
| Placebo | Mean Change From Baseline in Body Weight | 1.7 kilograms (kg) | Standard Error 0.53 |
p-value: <0.00195% CI: [-5.8, -2.9]Mixed Models Analysis
p-value: <0.00195% CI: [-8, -5]Mixed Models Analysis
p-value: <0.00195% CI: [-7.5, -4.5]Mixed Models Analysis
Secondary
Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles
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 MMRM for post-baseline measures: Variable = Baseline + Baseline HbA1c (\<=8.0%, \>8.0%) + SGLT2i Use (Yes/No) + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. 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 excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Morning Premeal - Fasting | -2.62 millimoles per liter per day(mmol/L/day) | Standard Error 0.127 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Evening 2-hour Postmeal | -3.97 millimoles per liter per day(mmol/L/day) | Standard Error 0.347 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Evening Premeal | -2.84 millimoles per liter per day(mmol/L/day) | Standard Error 0.264 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Morning 2-hour Postmeal | -4.78 millimoles per liter per day(mmol/L/day) | Standard Error 0.3 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Bedtime | -3.41 millimoles per liter per day(mmol/L/day) | Standard Error 0.287 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Midday Premeal | -2.87 millimoles per liter per day(mmol/L/day) | Standard Error 0.247 |
| 10 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Midday 2-hour Postmeal | -4.05 millimoles per liter per day(mmol/L/day) | Standard Error 0.318 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Evening 2-hour Postmeal | -4.52 millimoles per liter per day(mmol/L/day) | Standard Error 0.351 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Midday 2-hour Postmeal | -4.10 millimoles per liter per day(mmol/L/day) | Standard Error 0.325 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Midday Premeal | -3.52 millimoles per liter per day(mmol/L/day) | Standard Error 0.258 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Evening Premeal | -3.64 millimoles per liter per day(mmol/L/day) | Standard Error 0.276 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Bedtime | -4.19 millimoles per liter per day(mmol/L/day) | Standard Error 0.297 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Morning 2-hour Postmeal | -5.34 millimoles per liter per day(mmol/L/day) | Standard Error 0.306 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Morning Premeal - Fasting | -2.53 millimoles per liter per day(mmol/L/day) | Standard Error 0.132 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Midday 2-hour Postmeal | -3.65 millimoles per liter per day(mmol/L/day) | Standard Error 0.335 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Morning Premeal - Fasting | -2.80 millimoles per liter per day(mmol/L/day) | Standard Error 0.136 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Morning 2-hour Postmeal | -5.05 millimoles per liter per day(mmol/L/day) | Standard Error 0.313 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Midday Premeal | -3.26 millimoles per liter per day(mmol/L/day) | Standard Error 0.263 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Evening Premeal | -3.20 millimoles per liter per day(mmol/L/day) | Standard Error 0.285 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Evening 2-hour Postmeal | -4.42 millimoles per liter per day(mmol/L/day) | Standard Error 0.367 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Bedtime | -3.85 millimoles per liter per day(mmol/L/day) | Standard Error 0.307 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Midday Premeal | -1.32 millimoles per liter per day(mmol/L/day) | Standard Error 0.253 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Bedtime | -1.71 millimoles per liter per day(mmol/L/day) | Standard Error 0.298 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Evening 2-hour Postmeal | -1.47 millimoles per liter per day(mmol/L/day) | Standard Error 0.346 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Morning 2-hour Postmeal | -2.57 millimoles per liter per day(mmol/L/day) | Standard Error 0.3 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Morning Premeal - Fasting | -2.22 millimoles per liter per day(mmol/L/day) | Standard Error 0.131 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Evening Premeal | -0.95 millimoles per liter per day(mmol/L/day) | Standard Error 0.271 |
| Placebo | Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles | Midday 2-hour Postmeal | -1.46 millimoles per liter per day(mmol/L/day) | Standard Error 0.322 |
Secondary
Mean Change From Baseline in Fasting Serum Glucose
LSMean was calculated using MMRM for post-baseline measures: Variable = Baseline + Baseline HbA1c (\<=8.0%, \>8.0%) + SGLT2i Use (Yes/No) + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. 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 excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Mean Change From Baseline in Fasting Serum Glucose | -45.5 milligram per deciliter (mg/dL) | Standard Error 3.73 |
| 15 mg Tirzepatide | Mean Change From Baseline in Fasting Serum Glucose | -52.5 milligram per deciliter (mg/dL) | Standard Error 3.87 |
| Placebo | Mean Change From Baseline in Fasting Serum Glucose | -51.0 milligram per deciliter (mg/dL) | Standard Error 3.94 |
| Placebo | Mean Change From Baseline in Fasting Serum Glucose | -23.7 milligram per deciliter (mg/dL) | Standard Error 3.84 |
p-value: <0.00195% CI: [-32.4, -11.3]Mixed Models Analysis
p-value: <0.00195% CI: [-39.6, -18.1]Mixed Models Analysis
p-value: <0.00195% CI: [-38.2, -16.5]Mixed Models Analysis
Secondary
Mean Change From Baseline in HbA1c (Tirzepatide 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. LS mean was calculated using MMRM for post-baseline measures: Variable = Baseline + SGLT2i Use (Yes/No) + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. 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 excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Mean Change From Baseline in HbA1c (Tirzepatide 5 mg) | -23.0 mmol/mol | Standard Error 1.329 |
| 15 mg Tirzepatide | Mean Change From Baseline in HbA1c (Tirzepatide 5 mg) | -9.96 mmol/mol | Standard Error 1.34 |
p-value: <0.00195% CI: [-16.8, -9.34]Mixed Models Analysis
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 with baseline and post-baseline value at the specified time point for this outcome excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥10% | 8.06 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥10% | 21.05 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Weight Loss of ≥10% | 25.45 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Weight Loss of ≥10% | 0.00 percentage of participants |
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 with baseline and post-baseline value at the specified time point for this outcome excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥15% | 4.84 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥15% | 5.26 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Weight Loss of ≥15% | 9.09 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Weight Loss of ≥15% | 0.00 percentage of participants |
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 with baseline and post-baseline value at the specified time point for this outcome excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥5% | 25.81 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss of ≥5% | 49.12 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Weight Loss of ≥5% | 60.00 percentage of participants |
| Placebo | Percentage of Participants Who Achieved Weight Loss of ≥5% | 1.72 percentage of participants |
Secondary
Percentage of Participants With HbA1c <5.7% (39 mmol/Mol) [Tirzepatide 10 mg or 15 mg]
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 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 with baseline and post-baseline value at the specified time point for this outcome excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants With HbA1c <5.7% (39 mmol/Mol) [Tirzepatide 10 mg or 15 mg] | 17.54 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c <5.7% (39 mmol/Mol) [Tirzepatide 10 mg or 15 mg] | 25.45 percentage of participants |
| Placebo | Percentage of Participants With HbA1c <5.7% (39 mmol/Mol) [Tirzepatide 10 mg or 15 mg] | 0.00 percentage of participants |
Secondary
Percentage of Participants With HbA1c <5.7% (39 mmol/Mol) [Tirzepatide 5 mg]
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 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 with baseline and post-baseline value at the specified time point for this outcome excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants With HbA1c <5.7% (39 mmol/Mol) [Tirzepatide 5 mg] | 9.68 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c <5.7% (39 mmol/Mol) [Tirzepatide 5 mg] | 0.00 percentage of participants |
Secondary
Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.0 mmol/L [54 mg/dL])
Percentage of Participants with HbA1c ≤6.5%, Without Weight Gain \<0.1 kg and Without Hypoglycemia (Blood glucose \<3.0 mmol/L \[54 mg/dL\]) is reported here.
Time frame: 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 excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.0 mmol/L [54 mg/dL]) | 46.77 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.0 mmol/L [54 mg/dL]) | 70.18 percentage of participants |
| Placebo | Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.0 mmol/L [54 mg/dL]) | 61.82 percentage of participants |
| Placebo | Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.0 mmol/L [54 mg/dL]) | 1.72 percentage of participants |
Secondary
Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia)
Percentage of Participants with HbA1c ≤6.5%, Without Weight Gain \<0.1 kg and Without Hypoglycemia (Blood glucose \<3.9 mmol/L \[70 mg/dL\] or Severe Hypoglycemia) is reported here.
Time frame: 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 excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia) | 38.71 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia) | 57.89 percentage of participants |
| Placebo | Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia) | 43.64 percentage of participants |
| Placebo | Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia) | 1.72 percentage of participants |
Secondary
Percentage of Participants With HbA1c <7.0% (53 Millimole/Mole [mmol/Mol]) and ≤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 \<7.0% (53 millimole/mole \[mmol/mol\]) and ≤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 with baseline and post-baseline value at the specified time point for this outcome excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants With HbA1c <7.0% (53 Millimole/Mole [mmol/Mol]) and ≤6.5% (48 mmol/Mol) | HbA1c <7.0% | 75.81 percentage of participants |
| 10 mg Tirzepatide | Percentage of Participants With HbA1c <7.0% (53 Millimole/Mole [mmol/Mol]) and ≤6.5% (48 mmol/Mol) | HbA1c ≤6.5% | 59.68 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c <7.0% (53 Millimole/Mole [mmol/Mol]) and ≤6.5% (48 mmol/Mol) | HbA1c ≤6.5% | 77.19 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c <7.0% (53 Millimole/Mole [mmol/Mol]) and ≤6.5% (48 mmol/Mol) | HbA1c <7.0% | 78.95 percentage of participants |
| Placebo | Percentage of Participants With HbA1c <7.0% (53 Millimole/Mole [mmol/Mol]) and ≤6.5% (48 mmol/Mol) | HbA1c <7.0% | 78.18 percentage of participants |
| Placebo | Percentage of Participants With HbA1c <7.0% (53 Millimole/Mole [mmol/Mol]) and ≤6.5% (48 mmol/Mol) | HbA1c ≤6.5% | 69.09 percentage of participants |
| Placebo | Percentage of Participants With HbA1c <7.0% (53 Millimole/Mole [mmol/Mol]) and ≤6.5% (48 mmol/Mol) | HbA1c <7.0% | 17.24 percentage of participants |
| Placebo | Percentage of Participants With HbA1c <7.0% (53 Millimole/Mole [mmol/Mol]) and ≤6.5% (48 mmol/Mol) | HbA1c ≤6.5% | 6.90 percentage of participants |
Secondary
Percentage of Participants With HbA1c <7.0%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia)
Percentage of Participants with HbA1c \<7.0%, Without Weight Gain \<0.1 kg and Without Hypoglycemia (Blood Glucose \<3.9 mmol/L \[70 mg/dL\] or Severe Hypoglycemia) is reported here.
Time frame: 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 excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants With HbA1c <7.0%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia) | 51.61 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c <7.0%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia) | 57.89 percentage of participants |
| Placebo | Percentage of Participants With HbA1c <7.0%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia) | 47.27 percentage of participants |
| Placebo | Percentage of Participants With HbA1c <7.0%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia) | 5.17 percentage of participants |
Secondary
Percentage of Participants With HbA1c <7.0%, Without Weight Gain (<0.1 Kilogram [kg]) and Without Hypoglycemia, (Blood Glucose <3.0 mmol/L <54 Milligram/Deciliter [mg/dL])
Percentage of Participants with HbA1c \<7.0%, Without Weight Gain (\<0.1 Kilogram \[kg\]) and Without Hypoglycemia, (Blood Glucose \<3.0 mmol/L \<54 Milligram/Deciliter \[mg/dL\]) is reported here
Time frame: 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 excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants With HbA1c <7.0%, Without Weight Gain (<0.1 Kilogram [kg]) and Without Hypoglycemia, (Blood Glucose <3.0 mmol/L <54 Milligram/Deciliter [mg/dL]) | 59.68 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c <7.0%, Without Weight Gain (<0.1 Kilogram [kg]) and Without Hypoglycemia, (Blood Glucose <3.0 mmol/L <54 Milligram/Deciliter [mg/dL]) | 70.18 percentage of participants |
| Placebo | Percentage of Participants With HbA1c <7.0%, Without Weight Gain (<0.1 Kilogram [kg]) and Without Hypoglycemia, (Blood Glucose <3.0 mmol/L <54 Milligram/Deciliter [mg/dL]) | 67.27 percentage of participants |
| Placebo | Percentage of Participants With HbA1c <7.0%, Without Weight Gain (<0.1 Kilogram [kg]) and Without Hypoglycemia, (Blood Glucose <3.0 mmol/L <54 Milligram/Deciliter [mg/dL]) | 5.17 percentage of participants |
Secondary
Percent Change From Baseline in Daily Mean Insulin Glargine Dose
LS Mean was calculated using MMRM for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Baseline HbA1c (\<=8.0%, \>8.0%) + SGLT2i Use (Yes/No) + 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 excluding participants discontinuing study drug due to inadvertent enrollment and data after permanent discontinuation of study drug or initiation of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Percent Change From Baseline in Daily Mean Insulin Glargine Dose | 23.90 percent change | Standard Error 6.424 |
| 15 mg Tirzepatide | Percent Change From Baseline in Daily Mean Insulin Glargine Dose | 21.95 percent change | Standard Error 6.471 |
| Placebo | Percent Change From Baseline in Daily Mean Insulin Glargine Dose | 18.21 percent change | Standard Error 6.364 |
| Placebo | Percent Change From Baseline in Daily Mean Insulin Glargine Dose | 69.28 percent change | Standard Error 8.826 |