Obesity, Overweight
Conditions
Keywords
Metabolism and Nutrition, Disorder, Prediabetes, Diet, Exercise
Brief summary
The main purpose of this phase 3b study is to evaluate the efficacy and safety of tirzepatide compared with semaglutide in adult participants who have obesity or overweight with weight related comorbidities without Type 2 Diabetes. The study will last around 74 weeks.
Interventions
DRUGTirzepatide
Administered SC
DRUGSemaglutide
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 3b
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a body mass index (BMI) of ≥30 kilogram per square meter (kg/m²) or ≥27 kg/m² and previously diagnosed with at least one of the following weight related comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease * Have a history of at least 1 unsuccessful dietary effort to lose body weight
Exclusion criteria
* Diabetes mellitus * Change in body weight greater than 5 kg within 3 months prior to starting study * Obesity induced by other endocrinologic disorders or monogenetic or syndromic forms of obesity * History of pancreatitis * Family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2) * History of significant active or unstable major depressive disorder (MDD) or other severe psychiatric disorder within the last 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight | Baseline, Week 72 | Percent change from baseline in body weight was reported. Least Squares (LS) mean was determined using ANCOVA model with Baseline + Baseline BMI Group 1 + Sex + Pre diabetes status at randomization + Treatment (Type III sum of squares) as variables. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieve ≥15% Body Weight Reduction | Week 72 | Percentage of participants who achieved ≥15% body weight reduction (observed values) was reported. |
| Percentage of Participants Who Achieve ≥20% Body Weight Reduction | Week 72 | Percentage of participants who achieved ≥20% body weight reduction (observed values) was reported. |
| Percentage of Participants Who Achieve ≥25% Body Weight Reduction | Week 72 | Percentage of participants who achieved ≥25% body weight reduction (observed values) was reported. |
| Percentage of Participants Who Achieve ≥10% Body Weight Reduction | Week 72 | Percentage of participants who achieved ≥10% body weight reduction (observed values) was reported. |
| Percentage of Participants Who Achieve ≥30% Body Weight Reduction | Week 72 | Percentage of participants who achieved ≥30% body weight reduction (observed values) was reported. |
| Change From Baseline in Body Mass Index (BMI) | Baseline, Week 72 | Change from baseline in BMI was reported. LS mean was determined using Mixed Model Repeated Measures (MMRM) model using Baseline + Sex + Pre diabetes status at randomization + Treatment + Time + Treatment\*Time(Type III sum of squares) as variables. |
| Percent Change From Baseline in Body Weight Comparing 15 mg Tirzepatide and 2.4 mg Semaglutide | Baseline, Week 72 | Percent change from baseline in body weight comparing 15mg of Tirzepatide and 2.4 mg Semaglutide was reported. The treatment effect for tirzepatide versus semaglutide for percent change in body weight was also evaluated assuming that participants had stayed on treatment and reached the highest dose of treatment. LS mean was determined by MMRM model using Baseline + Sex + Pre diabetes status at randomization + Baseline BMI Group 1 + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. |
| Change From Baseline in Waist Circumference in Centimeter | Baseline, Week 72 | Change from baseline in waist circumference in centimeter was reported. LS mean was determined using ANCOVA model with Baseline + Baseline BMI Group 1 + Sex + Pre diabetes status at randomization + Treatment (Type III sum of squares) as variables. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 15 mg or MTD - Tirzepatide Participants received a starting dose of 2.5 mg tirzepatide administered SC QW for 4 weeks, then the dose was increased by 2.5 mg every 4 weeks (2.5 to 5 to 7.5 to 10 to 12.5 to 15 mg) up to 15 mg QW or MTD (10 mg or 15 mg) until Week 72. | 374 |
| 2.4 mg or MTD - Semaglutide Participants received a starting dose of 0.25 mg semaglutide administered SC QW for 4 weeks, then the dose was increased every 4 weeks (0.25 to 0.5 to 1.0 to 1.7 to 2.4 mg) up to 2.4 mg QW or MTD (1.7 mg or 2.4 mg) until Week 72. | 376 |
| Total | 750 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 6 |
| Overall Study | Assigned Treatment by Mistake | 5 | 3 |
| Overall Study | Lost to Follow-up | 16 | 18 |
| Overall Study | Non-Compliance With Study Drug | 1 | 1 |
| Overall Study | Participant was Out of the Country | 0 | 1 |
| Overall Study | Pregnancy | 1 | 2 |
| Overall Study | Withdrawal by Subject | 27 | 26 |
Baseline characteristics
| Characteristic | 15 mg or MTD - Tirzepatide | Total | 2.4 mg or MTD - Semaglutide |
|---|---|---|---|
| Age, Continuous | 45.00 years STANDARD_DEVIATION 12.94 | 44.70 years STANDARD_DEVIATION 12.84 | 44.40 years STANDARD_DEVIATION 12.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 93 Participants | 196 Participants | 103 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 281 Participants | 554 Participants | 273 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 6 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 18 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 77 Participants | 144 Participants | 67 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 11 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 276 Participants | 571 Participants | 295 Participants |
| Region of Enrollment United States | 374 Participants | 750 Participants | 376 Participants |
| Sex: Female, Male Female | 242 Participants | 485 Participants | 243 Participants |
| Sex: Female, Male Male | 132 Participants | 265 Participants | 133 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 374 | 0 / 376 |
| other Total, other adverse events | 255 / 374 | 267 / 376 |
| serious Total, serious adverse events | 18 / 374 | 13 / 376 |
Outcome results
Primary
Percent Change From Baseline in Body Weight
Percent change from baseline in body weight was reported. Least Squares (LS) mean was determined using ANCOVA model with Baseline + Baseline BMI Group 1 + Sex + Pre diabetes status at randomization + Treatment (Type III sum of squares) as variables.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg or MTD - Tirzepatide | Percent Change From Baseline in Body Weight | -20.2 Percent change | Standard Error 0.59 |
| 2.4 mg or MTD - Semaglutide | Percent Change From Baseline in Body Weight | -13.7 Percent change | Standard Error 0.59 |
95% CI: [-8.1, -4.9]
Secondary
Change From Baseline in Body Mass Index (BMI)
Change from baseline in BMI was reported. LS mean was determined using Mixed Model Repeated Measures (MMRM) model using Baseline + Sex + Pre diabetes status at randomization + Treatment + Time + Treatment\*Time(Type III sum of squares) as variables.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg or MTD - Tirzepatide | Change From Baseline in Body Mass Index (BMI) | -8.5 kilograms per meter square | Standard Error 0.24 |
| 2.4 mg or MTD - Semaglutide | Change From Baseline in Body Mass Index (BMI) | -6.0 kilograms per meter square | Standard Error 0.24 |
95% CI: [-3.2, -1.9]
Secondary
Change From Baseline in Waist Circumference in Centimeter
Change from baseline in waist circumference in centimeter was reported. LS mean was determined using ANCOVA model with Baseline + Baseline BMI Group 1 + Sex + Pre diabetes status at randomization + Treatment (Type III sum of squares) as variables.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg or MTD - Tirzepatide | Change From Baseline in Waist Circumference in Centimeter | -18.4 centimeters | Standard Error 0.61 |
| 2.4 mg or MTD - Semaglutide | Change From Baseline in Waist Circumference in Centimeter | -13.0 centimeters | Standard Error 0.66 |
95% CI: [-7.1, -3.6]
Secondary
Percentage of Participants Who Achieve ≥10% Body Weight Reduction
Percentage of participants who achieved ≥10% body weight reduction (observed values) was reported.
Time frame: Week 72
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 mg or MTD - Tirzepatide | Percentage of Participants Who Achieve ≥10% Body Weight Reduction | 87.7 Percentage of participants |
| 2.4 mg or MTD - Semaglutide | Percentage of Participants Who Achieve ≥10% Body Weight Reduction | 66.7 Percentage of participants |
Secondary
Percentage of Participants Who Achieve ≥15% Body Weight Reduction
Percentage of participants who achieved ≥15% body weight reduction (observed values) was reported.
Time frame: Week 72
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 mg or MTD - Tirzepatide | Percentage of Participants Who Achieve ≥15% Body Weight Reduction | 71.7 Percentage of participants |
| 2.4 mg or MTD - Semaglutide | Percentage of Participants Who Achieve ≥15% Body Weight Reduction | 45.0 Percentage of participants |
Secondary
Percentage of Participants Who Achieve ≥20% Body Weight Reduction
Percentage of participants who achieved ≥20% body weight reduction (observed values) was reported.
Time frame: Week 72
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 mg or MTD - Tirzepatide | Percentage of Participants Who Achieve ≥20% Body Weight Reduction | 55.0 Percentage of participants |
| 2.4 mg or MTD - Semaglutide | Percentage of Participants Who Achieve ≥20% Body Weight Reduction | 31.1 Percentage of participants |
Secondary
Percentage of Participants Who Achieve ≥25% Body Weight Reduction
Percentage of participants who achieved ≥25% body weight reduction (observed values) was reported.
Time frame: Week 72
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 mg or MTD - Tirzepatide | Percentage of Participants Who Achieve ≥25% Body Weight Reduction | 36.5 Percentage of participants |
| 2.4 mg or MTD - Semaglutide | Percentage of Participants Who Achieve ≥25% Body Weight Reduction | 18.6 Percentage of participants |
Secondary
Percentage of Participants Who Achieve ≥30% Body Weight Reduction
Percentage of participants who achieved ≥30% body weight reduction (observed values) was reported.
Time frame: Week 72
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 mg or MTD - Tirzepatide | Percentage of Participants Who Achieve ≥30% Body Weight Reduction | 23.0 Percentage of participants |
| 2.4 mg or MTD - Semaglutide | Percentage of Participants Who Achieve ≥30% Body Weight Reduction | 8.2 Percentage of participants |
Secondary
Percent Change From Baseline in Body Weight Comparing 15 mg Tirzepatide and 2.4 mg Semaglutide
Percent change from baseline in body weight comparing 15mg of Tirzepatide and 2.4 mg Semaglutide was reported. The treatment effect for tirzepatide versus semaglutide for percent change in body weight was also evaluated assuming that participants had stayed on treatment and reached the highest dose of treatment. LS mean was determined by MMRM model using Baseline + Sex + Pre diabetes status at randomization + Baseline BMI Group 1 + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.
Time frame: Baseline, Week 72
Population: All participants who received at least one dose of study drug and had evaluable data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg or MTD - Tirzepatide | Percent Change From Baseline in Body Weight Comparing 15 mg Tirzepatide and 2.4 mg Semaglutide | -21.8 Percent change | Standard Error 0.6 |
| 2.4 mg or MTD - Semaglutide | Percent Change From Baseline in Body Weight Comparing 15 mg Tirzepatide and 2.4 mg Semaglutide | -15.4 Percent change | Standard Error 0.6 |
95% CI: [-8, -4.7]