Type 2 Diabetes Mellitus
Conditions
Keywords
T2DM
Brief summary
The purpose of this study is to compare the effect of the study drug tirzepatide to insulin degludec on blood sugar levels in participants with type 2 diabetes. The study will last about 67 weeks and may include up to 22 visits.
Interventions
DRUGTirzepatide
Administered SC
DRUGInsulin Degludec
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must: * Have been diagnosed with type 2 diabetes mellitus (T2DM) * Have HbA1c between ≥7.0% and ≤10.5% * Be on stable treatment with unchanged dose of metformin or metformin plus an SGLT-2 inhibitor for at least 3 months before screening * Be of stable weight (± 5%) for at least 3 months before screening * Have a BMI ≥25 kilograms per meter squared (kg/m2) at screening
Exclusion criteria
* Participants must not: * 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 acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) enzyme level \>3.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. Participants with nonalcoholic fatty liver disease (NAFLD) are eligible for participation in this trial only if their ALT level is ≤3.0 the ULN for the reference range * Have an estimated glomerular filtration rate \<45 mL/minute/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 any other diabetes medicines other than metformin, or metformin plus an SGLT-2 inhibitor during the last 3 months * 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 52 | 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 covariates Baseline + Pooled Country + Baseline Oral Antihyperglycemic Medication (OAM) Use (Metformin (Met), Met plus SGLT-2i) + Treatment + Time + Treatment\*Time (Type III sum of squares). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Body Weight | Baseline, Week 52 | LS mean was determined by MMRM model with Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as covariates. |
| Change From Baseline in Fasting Serum Glucose | Baseline, Week 52 | LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percentage of Participants Achieving an HbA1c Target Value of <7% | Week 52 | Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing. Missing endpoint measures are imputed by predictions from an MMRM analysis model using observed data in the efficacy analysis set and adjusted for Baseline Value, Pooled Country, Baseline OAM Use (Met, Met plus SGLT-2i), Treatment, Visit and Visit\*Treatment. |
| Change From Baseline in HbA1c (5 mg) | Baseline, Week 52 | 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 covariates Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percentage of Participants Who Achieved Weight Loss ≥5% | Week 52 | Percentage of Participants who Achieved Weight Loss ≥5% |
| Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Week 52 | DTSQc, an 8-item questionnaire, assesses relative change in treatment satisfaction perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia from baseline to week 52 or early termination.The treatment satisfaction score ranges from -18 to 18 where the higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. The hyperglycemia and hypoglycemia scores range from -3 to 3 where negative scores indicate fewer problems with blood glucose levels and positive scores indicate more problems than before. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline DTSQs + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment (Type III sum of squares). |
| 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 56) | 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 OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment, with log (exposure in days/365.25) as an offset variable. |
| Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | Baseline, Week 52 | 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. LS mean was determined by mixed-model repeated measures (MMRM) model with variables Baseline + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment + Time + Treatment\*Time (Type III sum of squares). |
Countries
Argentina, Austria, Greece, Hungary, Italy, Poland, Puerto Rico, Romania, South Korea, Spain, Taiwan, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 5 mg Tirzepatide 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. | 359 |
| 10 mg Tirzepatide 10 mg tirzepatide administered SC once a week. | 361 |
| 15 mg Tirzepatide 15 mg tirzepatide administered SC once a week SC. | 359 |
| Insulin Degludec Insulin degludec administered SC once a day. Doses were individualized and titrated according to protocol-defined targets.
The starting dose of insulin degludec was 10 IU/day ideally at bedtime, titrated to a fasting blood glucose (FBG) \<90 milligram per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm based on the last 3 FBG values. | 365 |
| Total | 1,444 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 7 | 3 | 1 |
| Overall Study | Death | 1 | 2 | 1 | 1 |
| Overall Study | Lost to Follow-up | 8 | 9 | 5 | 5 |
| Overall Study | Personal Reason | 2 | 3 | 1 | 3 |
| Overall Study | Physician Decision | 0 | 2 | 2 | 2 |
| Overall Study | Protocol Violation | 2 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 17 | 7 | 22 |
Baseline characteristics
| Characteristic | 5 mg Tirzepatide | 10 mg Tirzepatide | 15 mg Tirzepatide | Insulin Degludec | Total |
|---|---|---|---|---|---|
| Age, Continuous | 57.20 years STANDARD_DEVIATION 10.13 | 57.40 years STANDARD_DEVIATION 9.66 | 57.50 years STANDARD_DEVIATION 10.24 | 57.50 years STANDARD_DEVIATION 10.08 | 57.40 years STANDARD_DEVIATION 10.02 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 109 Participants | 108 Participants | 96 Participants | 108 Participants | 421 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 247 Participants | 253 Participants | 259 Participants | 256 Participants | 1015 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 4 Participants | 1 Participants | 8 Participants |
| Hemoglobin A1c | 8.17 Percentage of HbA1c STANDARD_DEVIATION 0.89 | 8.18 Percentage of HbA1c STANDARD_DEVIATION 0.89 | 8.21 Percentage of HbA1c STANDARD_DEVIATION 0.94 | 8.12 Percentage of HbA1c STANDARD_DEVIATION 0.94 | 8.17 Percentage of HbA1c STANDARD_DEVIATION 0.91 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 19 Participants | 20 Participants | 19 Participants | 78 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 12 Participants | 8 Participants | 11 Participants | 44 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 324 Participants | 329 Participants | 327 Participants | 332 Participants | 1312 Participants |
| Region of Enrollment Argentina | 57 Participants | 54 Participants | 56 Participants | 57 Participants | 224 Participants |
| Region of Enrollment Austria | 7 Participants | 8 Participants | 4 Participants | 8 Participants | 27 Participants |
| Region of Enrollment Greece | 33 Participants | 35 Participants | 35 Participants | 34 Participants | 137 Participants |
| Region of Enrollment Hungary | 36 Participants | 37 Participants | 37 Participants | 37 Participants | 147 Participants |
| Region of Enrollment Italy | 6 Participants | 8 Participants | 8 Participants | 8 Participants | 30 Participants |
| Region of Enrollment Poland | 33 Participants | 33 Participants | 33 Participants | 33 Participants | 132 Participants |
| Region of Enrollment Puerto Rico | 8 Participants | 7 Participants | 11 Participants | 9 Participants | 35 Participants |
| Region of Enrollment Romania | 54 Participants | 54 Participants | 53 Participants | 53 Participants | 214 Participants |
| Region of Enrollment South Korea | 9 Participants | 10 Participants | 8 Participants | 9 Participants | 36 Participants |
| Region of Enrollment Spain | 21 Participants | 21 Participants | 22 Participants | 22 Participants | 86 Participants |
| Region of Enrollment Taiwan | 9 Participants | 8 Participants | 10 Participants | 9 Participants | 36 Participants |
| Region of Enrollment Ukraine | 11 Participants | 11 Participants | 12 Participants | 11 Participants | 45 Participants |
| Region of Enrollment United States | 75 Participants | 75 Participants | 70 Participants | 75 Participants | 295 Participants |
| Sex: Female, Male Female | 158 Participants | 165 Participants | 165 Participants | 148 Participants | 636 Participants |
| Sex: Female, Male Male | 201 Participants | 196 Participants | 194 Participants | 217 Participants | 808 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 / 358 | 2 / 360 | 1 / 359 | 1 / 360 |
| other Total, other adverse events | 124 / 358 | 157 / 360 | 179 / 359 | 66 / 360 |
| serious Total, serious adverse events | 29 / 358 | 20 / 360 | 26 / 359 | 22 / 360 |
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 covariates Baseline + Pooled Country + Baseline Oral Antihyperglycemic Medication (OAM) Use (Metformin (Met), Met plus SGLT-2i) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 52
Population: All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date +7 days)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) | -2.20 Percentage of HbA1c | Standard Error 0.051 |
| 15 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) | -2.37 Percentage of HbA1c | Standard Error 0.05 |
| Insulin Degludec | Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) | -1.34 Percentage of HbA1c | Standard Error 0.049 |
p-value: <0.00195% CI: [-1, -0.72]Mixed Models Analysis
p-value: <0.00195% CI: [-1.17, -0.9]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight
LS mean was determined by MMRM model with Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as covariates.
Time frame: Baseline, Week 52
Population: All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date +7 days)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Change From Baseline in Body Weight | -7.5 Kilograms (kg) | Standard Error 0.37 |
| 15 mg Tirzepatide | Change From Baseline in Body Weight | -10.7 Kilograms (kg) | Standard Error 0.37 |
| Insulin Degludec | Change From Baseline in Body Weight | -12.9 Kilograms (kg) | Standard Error 0.37 |
| Insulin Degludec | Change From Baseline in Body Weight | 2.3 Kilograms (kg) | Standard Error 0.37 |
p-value: <0.00195% CI: [-10.8, -8.8]Mixed Models Analysis
p-value: <0.00195% CI: [-14, -11.9]Mixed Models Analysis
p-value: <0.00195% CI: [-16.2, -14.2]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Serum Glucose
LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 52
Population: All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date +7 days)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Change From Baseline in Fasting Serum Glucose | -48.2 milligram per Deciliter (mg/dL) | Standard Error 1.82 |
| 15 mg Tirzepatide | Change From Baseline in Fasting Serum Glucose | -54.8 milligram per Deciliter (mg/dL) | Standard Error 1.86 |
| Insulin Degludec | Change From Baseline in Fasting Serum Glucose | -59.2 milligram per Deciliter (mg/dL) | Standard Error 1.85 |
| Insulin Degludec | Change From Baseline in Fasting Serum Glucose | -55.7 milligram per Deciliter (mg/dL) | Standard Error 1.81 |
p-value: 0.00495% CI: [2.4, 12.5]Mixed Models Analysis
p-value: 0.75195% CI: [-4.3, 5.9]Mixed Models Analysis
p-value: 0.16895% CI: [-8.7, 1.5]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 covariates Baseline + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 52
Population: All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date +7 days)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 10 mg Tirzepatide | Change From Baseline in HbA1c (5 mg) | -1.93 Percentage of HbA1c | Standard Error 0.05 |
| 15 mg Tirzepatide | Change From Baseline in HbA1c (5 mg) | -1.34 Percentage of HbA1c | Standard Error 0.049 |
p-value: <0.00195% CI: [-0.73, -0.45]Mixed Models Analysis
Secondary
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score
DTSQc, an 8-item questionnaire, assesses relative change in treatment satisfaction perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia from baseline to week 52 or early termination.The treatment satisfaction score ranges from -18 to 18 where the higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. The hyperglycemia and hypoglycemia scores range from -3 to 3 where negative scores indicate fewer problems with blood glucose levels and positive scores indicate more problems than before. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline DTSQs + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment (Type III sum of squares).
Time frame: Week 52
Population: All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date +7 days)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 10 mg Tirzepatide | Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Treatment Satisfaction Score | 15.6 units on a scale | Standard Error 0.27 |
| 10 mg Tirzepatide | Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Hyperglycemia | -1.4 units on a scale | Standard Error 0.11 |
| 10 mg Tirzepatide | Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Hypoglycemia | -1.1 units on a scale | Standard Error 0.12 |
| 15 mg Tirzepatide | Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Hyperglycemia | -1.4 units on a scale | Standard Error 0.11 |
| 15 mg Tirzepatide | Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Hypoglycemia | -0.9 units on a scale | Standard Error 0.12 |
| 15 mg Tirzepatide | Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Treatment Satisfaction Score | 15.5 units on a scale | Standard Error 0.28 |
| Insulin Degludec | Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Hypoglycemia | -1.0 units on a scale | Standard Error 0.12 |
| Insulin Degludec | Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Hyperglycemia | -1.6 units on a scale | Standard Error 0.11 |
| Insulin Degludec | Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Treatment Satisfaction Score | 15.6 units on a scale | Standard Error 0.28 |
| Insulin Degludec | Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Hyperglycemia | -1.1 units on a scale | Standard Error 0.11 |
| Insulin Degludec | Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Treatment Satisfaction Score | 12.6 units on a scale | Standard Error 0.27 |
| Insulin Degludec | Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score | Hypoglycemia | -0.7 units on a scale | Standard Error 0.12 |
Comparison: Hyperglycemiap-value: 0.09695% CI: [-0.57, 0.05]ANCOVA
Comparison: Hyperglycemiap-value: 0.11395% CI: [-0.57, 0.06]ANCOVA
Comparison: Hyperglycemiap-value: 0.00395% CI: [-0.78, -0.16]ANCOVA
Comparison: Hypoglycemiap-value: 0.01495% CI: [-0.74, -0.08]ANCOVA
Comparison: Hypoglycemiap-value: 0.2895% CI: [-0.51, 0.15]ANCOVA
Comparison: Hypoglycemiap-value: 0.12995% CI: [-0.59, 0.07]ANCOVA
Comparison: Treatment Satisfaction Scorep-value: <0.00195% CI: [2.26, 3.75]ANCOVA
Comparison: Treatment Satisfaction Scorep-value: <0.00195% CI: [2.15, 3.65]ANCOVA
Comparison: Treatment Satisfaction Scorep-value: <0.00195% CI: [2.24, 3.74]ANCOVA
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. LS mean was determined by mixed-model repeated measures (MMRM) model with variables Baseline + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Pooled Country + Baseline OAM Use (Met, Met plus SGLT-2i) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 52
Population: All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date +7 days)
| 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 | -52.6 mg/dL | Standard Error 1.2 |
| 15 mg Tirzepatide | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | -59.7 mg/dL | Standard Error 1.22 |
| Insulin Degludec | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | -60.6 mg/dL | Standard Error 1.2 |
| Insulin Degludec | Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | -48.0 mg/dL | Standard Error 1.18 |
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. Imputed data includes observed value and imputed value if endpoint measure is missing. Missing endpoint measures are imputed by predictions from an MMRM analysis model using observed data in the efficacy analysis set and adjusted for Baseline Value, Pooled Country, Baseline OAM Use (Met, Met plus SGLT-2i), Treatment, Visit and Visit\*Treatment.
Time frame: Week 52
Population: All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date +7 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants Achieving an HbA1c Target Value of <7% | 82.44 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants Achieving an HbA1c Target Value of <7% | 89.71 percentage of participants |
| Insulin Degludec | Percentage of Participants Achieving an HbA1c Target Value of <7% | 92.63 percentage of participants |
| Insulin Degludec | Percentage of Participants Achieving an HbA1c Target Value of <7% | 61.25 percentage of participants |
p-value: <0.00195% CI: [2.38, 5.01]Regression, Logistic
p-value: <0.00195% CI: [4.55, 10.84]Regression, Logistic
p-value: <0.00195% CI: [6.65, 17.48]Regression, Logistic
Secondary
Percentage of Participants Who Achieved Weight Loss ≥5%
Percentage of Participants who Achieved Weight Loss ≥5%
Time frame: Week 52
Population: All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date +7 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss ≥5% | 66.01 percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss ≥5% | 83.71 percentage of participants |
| Insulin Degludec | Percentage of Participants Who Achieved Weight Loss ≥5% | 87.82 percentage of participants |
| Insulin Degludec | Percentage of Participants Who Achieved Weight Loss ≥5% | 6.27 percentage of participants |
p-value: <0.00195% CI: [18.35, 48.35]Regression, Logistic
p-value: <0.00195% CI: [47.56, 134.17]Regression, Logistic
p-value: <0.00195% CI: [64.73, 189.55]Regression, Logistic
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 OAM Use (Met, Met plus SGLT-2i) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment, with log (exposure in days/365.25) as an offset variable.
Time frame: Baseline through Safety Follow-Up (Up to Week 56)
Population: All randomized participants who received at least one dose of study drug and had a baseline and at least 1 post-baseline value, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or stopping study drug (last dose date +7 days)
| 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 | 0.0137 Episodes/participant/365.25 days | Standard Error 0.0056 |
| 15 mg Tirzepatide | Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia | 0.0108 Episodes/participant/365.25 days | Standard Error 0.0044 |
| Insulin Degludec | Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia | 0.0275 Episodes/participant/365.25 days | Standard Error 0.0143 |
| Insulin Degludec | Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia | 0.1020 Episodes/participant/365.25 days | Standard Error 0.0568 |