Type 2 Diabetes
Conditions
Keywords
glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), GIP/GLP-1 dual receptor agonist, T2DM
Brief summary
The purpose of this study is to compare the safety and efficacy of the study drug tirzepatide to insulin lispro (U100) three times a day in participants with type 2 diabetes that are already on insulin glargine (U100), with or without metformin.
Interventions
DRUGTirzepatide
Administered SC
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
* Have been diagnosed with type 2 diabetes mellitus (T2DM) * Have HbA1c between ≥7.5% and ≤11% * Have been treated for at least 90 days prior to day of screening with once or twice daily basal insulin with or without stable dose of metformin ≥1500 mg/day and up to maximum approved dose per country specific approved label, sulfonylureas or dipeptidyl peptidase 4 inhibitors * Be of stable weight (± 5%) for at least 90 days * Have a BMI ≥23 kilograms per meter squared (kg/m²) and ≤45 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 macular edema or nonproliferative diabetic retinopathy requiring immediate or urgent treatment * Have disorders associated with slowed emptying of the stomach, have had any stomach surgeries for the purpose of weight loss, or are chronically taking drugs that directly affect gastrointestinal motility * 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 * Have an estimated glomerular filtration rate \<30 mL/minute/1.73 m² \[for participants on metformin, estimated glomerular filtration rate \<45 mL/min/1.73 m2 (or lower than the country-specific threshold for using the protocol-required dose of metformin per local label)\]
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses of Tirzepatide 5 mg, 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 Metformin Use (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HbA1c Target Values <7.0% | Week 52 | 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 52 | LS mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Change From Baseline in Fasting Serum Glucose | Baseline, Week 52 | LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| 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 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 determined by MMRM model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Change From Baseline in HbA1c | 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. LS mean was determined by MMRM model with covariates Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + 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% is reported here. |
| Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score | Baseline, Week 52 | The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. PCS score is reported here. PCS domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS mean was determined by analysis of covariance (ANCOVA) model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares). |
| Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score | Baseline, Week 52 | The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. MCS consisted of social functioning, vitality, mental health, and role-emotional scales. MCS score is reported here. MCS domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS mean was determined by ANCOVA model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares). |
| Percentage of Participants Who Achieved HbA1c Target Value of <7.0% Without Hypoglycemia | 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. |
Countries
Argentina, Belgium, Brazil, Czechia, Germany, Greece, Hungary, Italy, Mexico, Puerto Rico, Romania, Russia, Slovakia, Spain, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 5 mg Tirzepatide Participants received 5 mg tirzepatide administered SC once a week. | 243 |
| 10 mg Tirzepatide Participants received 10 mg tirzepatide administered SC once a week. | 238 |
| 15 mg Tirzepatide Participants received 15 mg tirzepatide administered SC once a week. | 236 |
| Insulin Lispro Participants received Insulin lispro (U100) administered SC three times a day. | 711 |
| Total | 1,428 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 2 | 4 |
| Overall Study | Death | 3 | 3 | 1 | 11 |
| Overall Study | Lost to Follow-up | 1 | 2 | 1 | 6 |
| Overall Study | Missed study visits | 2 | 0 | 0 | 3 |
| Overall Study | Physician Decision | 1 | 0 | 2 | 5 |
| Overall Study | Pregnancy | 1 | 0 | 0 | 0 |
| Overall Study | Safety reasons | 1 | 0 | 0 | 0 |
| Overall Study | Sponsor's decision | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 4 | 4 | 58 |
Baseline characteristics
| Characteristic | Total | Insulin Lispro | 15 mg Tirzepatide | 10 mg Tirzepatide | 5 mg Tirzepatide |
|---|---|---|---|---|---|
| Age, Continuous | 58.80 years STANDARD_DEVIATION 9.75 | 59.00 years STANDARD_DEVIATION 9.74 | 58.20 years STANDARD_DEVIATION 9.62 | 59.60 years STANDARD_DEVIATION 9.41 | 58.00 years STANDARD_DEVIATION 10.18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 885 Participants | 446 Participants | 149 Participants | 142 Participants | 148 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 536 Participants | 261 Participants | 87 Participants | 93 Participants | 95 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 4 Participants | 0 Participants | 3 Participants | 0 Participants |
| Hemoglobin A1c | 8.80 Percentage of HbA1c STANDARD_DEVIATION 0.97 | 8.81 Percentage of HbA1c STANDARD_DEVIATION 0.96 | 8.74 Percentage of HbA1c STANDARD_DEVIATION 1.01 | 8.78 Percentage of HbA1c STANDARD_DEVIATION 0.98 | 8.89 Percentage of HbA1c STANDARD_DEVIATION 0.97 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 4 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 57 Participants | 26 Participants | 11 Participants | 9 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 15 Participants | 8 Participants | 2 Participants | 5 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 | 1345 Participants | 671 Participants | 220 Participants | 224 Participants | 230 Participants |
| Region of Enrollment Argentina | 417 Participants | 207 Participants | 70 Participants | 70 Participants | 70 Participants |
| Region of Enrollment Belgium | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Brazil | 281 Participants | 141 Participants | 46 Participants | 47 Participants | 47 Participants |
| Region of Enrollment Czechia | 57 Participants | 29 Participants | 9 Participants | 9 Participants | 10 Participants |
| Region of Enrollment Germany | 47 Participants | 24 Participants | 8 Participants | 8 Participants | 7 Participants |
| Region of Enrollment Greece | 15 Participants | 9 Participants | 2 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Hungary | 19 Participants | 9 Participants | 2 Participants | 4 Participants | 4 Participants |
| Region of Enrollment Italy | 6 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Mexico | 118 Participants | 59 Participants | 20 Participants | 20 Participants | 19 Participants |
| Region of Enrollment Romania | 78 Participants | 38 Participants | 12 Participants | 14 Participants | 14 Participants |
| Region of Enrollment Russia | 107 Participants | 52 Participants | 19 Participants | 17 Participants | 19 Participants |
| Region of Enrollment Slovakia | 83 Participants | 39 Participants | 15 Participants | 13 Participants | 16 Participants |
| Region of Enrollment Spain | 25 Participants | 14 Participants | 3 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Turkey | 4 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 169 Participants | 85 Participants | 28 Participants | 28 Participants | 28 Participants |
| Sex: Female, Male Female | 824 Participants | 398 Participants | 133 Participants | 149 Participants | 144 Participants |
| Sex: Female, Male Male | 604 Participants | 313 Participants | 103 Participants | 89 Participants | 99 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 | 3 / 243 | 3 / 238 | 1 / 236 | 11 / 708 |
| other Total, other adverse events | 94 / 243 | 116 / 238 | 121 / 236 | 99 / 708 |
| serious Total, serious adverse events | 20 / 243 | 16 / 238 | 17 / 236 | 81 / 708 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses of Tirzepatide 5 mg, 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 Metformin Use (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 52
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug. This analysis was planned to measure the outcome for pooled 5 mg, 10 mg and 15 mg tirzepatide.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pooled 5 mg/10 mg/15 mg Tirzepatide | Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) | -2.26 Percentage of HbA1c | Standard Error 0.048 |
| Insulin Lispro | Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg) | -1.16 Percentage of HbA1c | Standard Error 0.049 |
p-value: <0.00195% CI: [-1.24, -0.97]Mixed Models Analysis
Secondary
Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score
The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. MCS consisted of social functioning, vitality, mental health, and role-emotional scales. MCS score is reported here. MCS domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS mean was determined by ANCOVA model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares).
Time frame: Baseline, Week 52
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants 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 |
|---|---|---|---|
| Pooled 5 mg/10 mg/15 mg Tirzepatide | Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score | 0.3 score on a scale | Standard Error 0.59 |
| Insulin Lispro | Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score | 1.5 score on a scale | Standard Error 0.59 |
| 15 mg Tirzepatide | Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score | 0.7 score on a scale | Standard Error 0.62 |
| Insulin Lispro | Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score | -1.3 score on a scale | Standard Error 0.36 |
p-value: 0.0295% CI: [0.3, 2.9]ANCOVA
p-value: <0.00195% CI: [1.5, 4.2]ANCOVA
p-value: 0.00495% CI: [0.7, 3.5]ANCOVA
Secondary
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score
The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. PCS score is reported here. PCS domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS mean was determined by analysis of covariance (ANCOVA) model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares).
Time frame: Baseline, Week 52
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants 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 |
|---|---|---|---|
| Pooled 5 mg/10 mg/15 mg Tirzepatide | Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score | 1.0 score on a scale | Standard Error 0.46 |
| Insulin Lispro | Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score | 1.7 score on a scale | Standard Error 0.46 |
| 15 mg Tirzepatide | Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score | 1.7 score on a scale | Standard Error 0.48 |
| Insulin Lispro | Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score | -0.6 score on a scale | Standard Error 0.28 |
p-value: 0.00595% CI: [0.5, 2.6]ANCOVA
p-value: <0.00195% CI: [1.2, 3.3]ANCOVA
p-value: <0.00195% CI: [1.2, 3.3]ANCOVA
Secondary
Change From Baseline in Body Weight
LS mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 52
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants 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 |
|---|---|---|---|
| Pooled 5 mg/10 mg/15 mg Tirzepatide | Change From Baseline in Body Weight | -6.9 Kilograms (kg) | Standard Error 0.37 |
| Insulin Lispro | Change From Baseline in Body Weight | -9.9 Kilograms (kg) | Standard Error 0.37 |
| 15 mg Tirzepatide | Change From Baseline in Body Weight | -12.0 Kilograms (kg) | Standard Error 0.38 |
| Insulin Lispro | Change From Baseline in Body Weight | 3.8 Kilograms (kg) | Standard Error 0.22 |
p-value: <0.00195% CI: [-11.5, -9.9]Mixed Models Analysis
p-value: <0.00195% CI: [-14.5, -12.9]Mixed Models Analysis
p-value: <0.00195% CI: [-16.7, -15]Mixed Models Analysis
Secondary
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 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 determined by MMRM model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 52
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants 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 |
|---|---|---|---|
| Pooled 5 mg/10 mg/15 mg Tirzepatide | Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | -56.7 mg/dL/day | Standard Error 1.8 |
| Insulin Lispro | Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | -61.5 mg/dL/day | Standard Error 1.85 |
| 15 mg Tirzepatide | Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | 67.6 mg/dL/day | Standard Error 1.86 |
| Insulin Lispro | Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values | -55.8 mg/dL/day | Standard Error 1.13 |
p-value: 0.68295% CI: [-5, 3.3]Mixed Models Analysis
p-value: 0.0195% CI: [-9.9, -1.4]Mixed Models Analysis
p-value: <0.00195% CI: [-16, -7.5]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Serum Glucose
LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 52
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants 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 |
|---|---|---|---|
| Pooled 5 mg/10 mg/15 mg Tirzepatide | Change From Baseline in Fasting Serum Glucose | -33.2 milligram per Deciliter (mg/dL) | Standard Error 3.28 |
| Insulin Lispro | Change From Baseline in Fasting Serum Glucose | -43.0 milligram per Deciliter (mg/dL) | Standard Error 3.32 |
| 15 mg Tirzepatide | Change From Baseline in Fasting Serum Glucose | -41.6 milligram per Deciliter (mg/dL) | Standard Error 3.42 |
| Insulin Lispro | Change From Baseline in Fasting Serum Glucose | -10.0 milligram per Deciliter (mg/dL) | Standard Error 1.99 |
p-value: <0.00195% CI: [-30.8, -15.7]Mixed Models Analysis
p-value: <0.00195% CI: [-40.6, -25.4]Mixed Models Analysis
p-value: <0.00195% CI: [-39.3, -23.8]Mixed Models Analysis
Secondary
Change From Baseline in HbA1c
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 determined by MMRM model with covariates Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 52
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants 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 |
|---|---|---|---|
| Pooled 5 mg/10 mg/15 mg Tirzepatide | Change From Baseline in HbA1c | -2.05 Percentage of HbA1c | Standard Error 0.082 |
| Insulin Lispro | Change From Baseline in HbA1c | -2.27 Percentage of HbA1c | Standard Error 0.083 |
| 15 mg Tirzepatide | Change From Baseline in HbA1c | -2.46 Percentage of HbA1c | Standard Error 0.084 |
| Insulin Lispro | Change From Baseline in HbA1c | -1.16 Percentage of HbA1c | Standard Error 0.049 |
p-value: <0.00195% CI: [-1.08, -0.7]Mixed Models Analysis
p-value: <0.00195% CI: [-1.3, -0.92]Mixed Models Analysis
p-value: <0.00195% CI: [-1.49, -1.11]Mixed Models Analysis
Secondary
Percentage of Participants Who Achieved HbA1c Target Value of <7.0% Without Hypoglycemia
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 52
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pooled 5 mg/10 mg/15 mg Tirzepatide | Percentage of Participants Who Achieved HbA1c Target Value of <7.0% Without Hypoglycemia | 52.70 Percentage of participants |
| Insulin Lispro | Percentage of Participants Who Achieved HbA1c Target Value of <7.0% Without Hypoglycemia | 70.05 Percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieved HbA1c Target Value of <7.0% Without Hypoglycemia | 75.12 Percentage of participants |
| Insulin Lispro | Percentage of Participants Who Achieved HbA1c Target Value of <7.0% Without Hypoglycemia | 13.41 Percentage of participants |
p-value: <0.00195% CI: [5.66, 11.83]Regression, Logistic
p-value: <0.00195% CI: [11.44, 24.96]Regression, Logistic
p-value: <0.00195% CI: [14.49, 32.93]Regression, Logistic
Secondary
Percentage of Participants Who Achieved Weight Loss ≥5%
Percentage of Participants who Achieved Weight Loss ≥5% is reported here.
Time frame: Week 52
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pooled 5 mg/10 mg/15 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss ≥5% | 64.19 Percentage of participants |
| Insulin Lispro | Percentage of Participants Who Achieved Weight Loss ≥5% | 79.21 Percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants Who Achieved Weight Loss ≥5% | 83.15 Percentage of participants |
| Insulin Lispro | Percentage of Participants Who Achieved Weight Loss ≥5% | 6.34 Percentage of participants |
p-value: <0.00195% CI: [18.36, 43.46]Regression, Logistic
p-value: <0.00195% CI: [36.76, 94.39]Regression, Logistic
p-value: <0.00195% CI: [47.49, 127.33]Regression, Logistic
Secondary
Percentage of Participants With HbA1c Target Values <7.0%
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 52
Population: All randomly assigned participants who took at least 1 dose of study drug and had a baseline and at least 1 post-baseline value for this analysis, excluding participants discontinuing study drug due to inadvertent enrollment and data after initiating rescue antihyperglycemic medication or prematurely stopping study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pooled 5 mg/10 mg/15 mg Tirzepatide | Percentage of Participants With HbA1c Target Values <7.0% | 61.04 Percentage of participants |
| Insulin Lispro | Percentage of Participants With HbA1c Target Values <7.0% | 75.64 Percentage of participants |
| 15 mg Tirzepatide | Percentage of Participants With HbA1c Target Values <7.0% | 79.86 Percentage of participants |
| Insulin Lispro | Percentage of Participants With HbA1c Target Values <7.0% | 36.69 Percentage of participants |
p-value: <0.000195% CI: [2.25, 4.36]Regression, Logistic
p-value: <0.000195% CI: [4.27, 8.88]Regression, Logistic
p-value: <0.000195% CI: [5.37, 11.75]Regression, Logistic