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| ID | Type | Description | Link |
|---|---|---|---|
| I8F-MC-GPGT | Other Identifier | Eli Lilly and Company | |
| 2018-003343-37 | EudraCT Number |
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This is a study for participants with type 2 diabetes mellitus. The main purpose of this study is to learn more about how tirzepatide, semaglutide and placebo affect the body's ability to respond to blood sugar levels after a meal. The study will last up to 40 weeks, including a 28-week treatment period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tirzepatide 15 mg | Experimental | Participants received 15 milligram (mg) tirzepatide administered subcutaneously (SC) once weekly for 28 weeks. |
|
| Semaglutide 1 mg | Active Comparator | Participants received 1 mg Semaglutide administered SC once weekly for 28 weeks. |
|
| Placebo | Placebo Comparator | Participants received Placebo administered SC once weekly for 28 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tirzepatide | Drug | Administered SC |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Total Clamp Disposition Index (cDI) | cDI is defined as the product of the M-value derived from the hyperinsulinemic euglycemic clamp over the last 30 minutes and total insulin secretion (ISR AUC0-120min) derived from the insulin secretion rate based on C-peptide using the using the deconvolution technique divided by the total glucose AUC0-120min from the hyperglycemic clamp portion of the study. Least squares (LS) mean was determined by analysis of covariance (ANCOVA) model for endpoint measures: log(Actual Measurement/Baseline) = log(Baseline) + Treatment (Type III sum of squares). | Baseline, Week 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Fasting Glucose | Fasting glucose is a test to determine sugar levels in blood sample after an overnight fast. Fasting glucose was measured prior to standardized mixed-meal tolerance tests (sMMTT). LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares). | Baseline, Week 28 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Profil Institut für Stoffwechselforschung | Neuss | North Rhine-Westphalia | 41460 | Germany | ||
| Profil Mainz GmbH & Co. KG |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36857477 | Derived | Heise T, DeVries JH, Urva S, Li J, Pratt EJ, Thomas MK, Mather KJ, Karanikas CA, Dunn J, Haupt A, Milicevic Z, Coskun T. Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes. Diabetes Care. 2023 May 1;46(5):998-1004. doi: 10.2337/dc22-1710. | |
| 35468322 | Derived | Heise T, Mari A, DeVries JH, Urva S, Li J, Pratt EJ, Coskun T, Thomas MK, Mather KJ, Haupt A, Milicevic Z. Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):418-429. doi: 10.1016/S2213-8587(22)00085-7. Epub 2022 Apr 22. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Tirzepatide 15 mg | Participants received 15 milligram (mg) Tirzepatide administered subcutaneously (SC) once weekly for 28 weeks. |
| FG001 | Semaglutide 1 mg | Participants received 1 mg Semaglutide administered SC once weekly for 28 weeks. |
| FG002 | Placebo | Participants received Placebo administered SC once weekly for 28 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All randomized participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tirzepatide 15 mg | Participants received 15 mg Tirzepatide administered SC once weekly for 28 weeks. |
| BG001 | Semaglutide 1 mg | Participants received 1 mg Semaglutide administered SC once weekly for 28 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Total Clamp Disposition Index (cDI) | cDI is defined as the product of the M-value derived from the hyperinsulinemic euglycemic clamp over the last 30 minutes and total insulin secretion (ISR AUC0-120min) derived from the insulin secretion rate based on C-peptide using the using the deconvolution technique divided by the total glucose AUC0-120min from the hyperglycemic clamp portion of the study. Least squares (LS) mean was determined by analysis of covariance (ANCOVA) model for endpoint measures: log(Actual Measurement/Baseline) = log(Baseline) + Treatment (Type III sum of squares). | All randomly assigned participants who received at least 1 dose of study drug and have evaluable data. | Posted | Least Squares Mean | Standard Error | pmol*m-2*L*min-2*kg-1 | Baseline, Week 28 |
|
Up to Week 32
All randomly assigned participants who received at least 1 dose of study drug and have evaluable data.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received Placebo administered SC once weekly for 28 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA 23.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 | ClinicalTrials.gov@lilly.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 10, 2020 | May 31, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 27, 2021 | May 31, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000098860 | Tirzepatide |
| C000591245 | semaglutide |
| ID | Term |
|---|---|
| D000067757 | Glucagon-Like Peptide-1 Receptor |
| D000067756 | Glucagon-Like Peptide Receptors |
| D043562 | Receptors, G-Protein-Coupled |
| D011956 | Receptors, Cell Surface |
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| Semaglutide | Drug | Administered SC |
|
| Placebo | Drug | Administered SC |
|
| Change From Baseline in Postmeal Glucose | Total AUC from time zero to 240 minutes after start of the meal [AUC0-240min]) during sMMTT was evaluated. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares) and ANOVA model for baseline measures: Variable = Treatment (Type III sum of squares). | Baseline, Week 28 |
| Change From Baseline in Hemoglobin A1c (HbA1c) | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by mixed model repeated measures; (MMRM) model for post-baseline measures: Variable = Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). | Baseline, Week 28 |
| Change From Baseline in Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min) | Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min) will be determined from C-peptide concentrations using the deconvolution technique. LS mean was determined by ANCOVA model for endpoint measures: log(Actual Measurement/Baseline) = log(Baseline) + Treatment (Type III sum of squares). | Baseline and Week 28 |
| Change From Baseline in Hyperinsulinemic Euglycemic Clamp M-value | Hyperinsulinemic euglycemic clamp M-value is calculated from glucose infusion rate (GIR) over the last 30 minutes, corresponding to steady-state (+150 to +180 minutes), corrected for urine loss and space. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares). | Baseline, Week 28 |
| Change From Baseline in Glucagon Concentration at Fasting | Glucagon concentration was measured prior to sMMTT. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares). | Baseline and Week 28 |
| Change From Baseline in Glucagon Concentration at Postmeal | Total AUC from time zero to 240 minutes after start of the meal [AUC0-240min]) during sMMTT. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares). | Baseline and Week 28 |
| Change From Baseline in Food Intake During Ad Libitum Meal | Ad libitum meal served buffet-style. Food intake was recorded during a 45 minute period. The sum of the caloric breakdown (carbohydrates, protein, and fats) was calculated from the respective nutritional information of the food items. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). | Baseline, Week 28 |
| Mainz |
| Rhineland-Palatinate |
| 55116 |
| Germany |
| Lost to Follow-up |
|
| BG002 | Placebo | Participants received Placebo administered SC once weekly for 28 weeks. |
| BG003 | Total | Total of all reporting groups |
| Participants |
| No |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants |
|
| HbA1c (%) | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. | Mean | Standard Deviation | percentage |
|
| OG001 | Semaglutide 1 mg | Participants received 1 mg Semaglutide administered SC once weekly for 28 weeks. |
| OG002 | Placebo | Participants received Placebo administered SC once weekly for 28 weeks. |
|
|
|
| Secondary | Change From Baseline in Fasting Glucose | Fasting glucose is a test to determine sugar levels in blood sample after an overnight fast. Fasting glucose was measured prior to standardized mixed-meal tolerance tests (sMMTT). LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares). | All randomly assigned participants who received at least 1 dose of study drug and have evaluable data. | Posted | Least Squares Mean | Standard Error | milligrams per decilitre (mg/dL) | Baseline, Week 28 |
|
|
|
|
| Secondary | Change From Baseline in Postmeal Glucose | Total AUC from time zero to 240 minutes after start of the meal [AUC0-240min]) during sMMTT was evaluated. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares) and ANOVA model for baseline measures: Variable = Treatment (Type III sum of squares). | All randomly assigned participants who received at least 1 dose of study drug and have evaluable data. | Posted | Least Squares Mean | Standard Error | Milligrams per decilitre*minute | Baseline, Week 28 |
|
|
|
|
| Secondary | Change From Baseline in Hemoglobin A1c (HbA1c) | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by mixed model repeated measures; (MMRM) model for post-baseline measures: Variable = Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). | All randomly assigned participants who received at least 1 dose of study drug and have evaluable data. | Posted | Least Squares Mean | Standard Error | % of HbA1c | Baseline, Week 28 |
|
|
|
|
| Secondary | Change From Baseline in Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min) | Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min) will be determined from C-peptide concentrations using the deconvolution technique. LS mean was determined by ANCOVA model for endpoint measures: log(Actual Measurement/Baseline) = log(Baseline) + Treatment (Type III sum of squares). | All randomly assigned participants who received at least 1 dose of study drug and have evaluable data. | Posted | Least Squares Mean | Standard Error | pmol/min/m^2 | Baseline and Week 28 |
|
|
|
|
| Secondary | Change From Baseline in Hyperinsulinemic Euglycemic Clamp M-value | Hyperinsulinemic euglycemic clamp M-value is calculated from glucose infusion rate (GIR) over the last 30 minutes, corresponding to steady-state (+150 to +180 minutes), corrected for urine loss and space. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares). | All randomly assigned participants who received at least 1 dose of study drug and have evaluable data. | Posted | Least Squares Mean | Standard Error | umol/min/kg [body weight] | Baseline, Week 28 |
|
|
|
|
| Secondary | Change From Baseline in Glucagon Concentration at Fasting | Glucagon concentration was measured prior to sMMTT. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares). | All randomly assigned participants who received at least 1 dose of study drug and have evaluable data. | Posted | Least Squares Mean | Standard Error | picomoles per litre (pmol/L) | Baseline and Week 28 |
|
|
|
|
| Secondary | Change From Baseline in Glucagon Concentration at Postmeal | Total AUC from time zero to 240 minutes after start of the meal [AUC0-240min]) during sMMTT. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares). | All randomly assigned participants who received at least 1 dose of study drug and have evaluable data. | Posted | Least Squares Mean | Standard Error | (pmol/L)*min | Baseline and Week 28 |
|
|
|
|
| Secondary | Change From Baseline in Food Intake During Ad Libitum Meal | Ad libitum meal served buffet-style. Food intake was recorded during a 45 minute period. The sum of the caloric breakdown (carbohydrates, protein, and fats) was calculated from the respective nutritional information of the food items. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). | All randomly assigned participants who received at least 1 dose of study drug and have evaluable data. | Posted | Least Squares Mean | Standard Error | kilocalorie (kcal) | Baseline, Week 28 |
|
|
|
|
| 0 |
| 28 |
| 2 |
| 28 |
| 18 |
| 28 |
| EG001 | Semaglutide 1 mg | Participants received 1 mg Semaglutide administered SC once weekly for 28 weeks. | 0 | 44 | 0 | 44 | 43 | 44 |
| EG002 | Tirzepatide 15 mg | Participants received 15 mg Tirzepatide administered SC once weekly for 28 weeks. | 0 | 45 | 1 | 45 | 41 | 45 |
| Subacute pancreatitis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Ureterolithiasis | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Early satiety | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Injection site haematoma | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Abnormal loss of weight | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
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| D004700 | Endocrine System Diseases |
| D008565 | Membrane Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011964 | Receptors, Gastrointestinal Hormone |
| D018000 | Receptors, Peptide |
| Least Squares Mean Difference |
| -47.1 |
| 2-Sided |
| 95 |
| -54.6 |
| -39.5 |
| Other |
| ANCOVA | 0.006 | Least Squares Mean Difference | -9.0 | 2-Sided | 95 | -15.4 | -2.6 | Other |
| Least Squares Mean Difference |
| -17873.2 |
| 2-Sided |
| 95 |
| -20239.0 |
| -15507.4 |
| Other |
| ANCOVA | 0.002 | Least Squares Mean Difference | -3177.1 | 2-Sided | 95 | -5194.3 | -1159.8 | Other |
| Least Squares Mean Difference |
| -2.33 |
| 2-Sided |
| 95 |
| -2.58 |
| -2.08 |
| Other |
| Mixed Models Analysis | <0.001 | Least Squares Mean Difference | -0.41 | 2-Sided | 95 | -0.63 | -0.19 | Other |
| ANCOVA |
Data were analysed with ANCOVA in log transformed data. |
| <0.001 |
| Least Squares Mean Difference |
| 381.23 |
| Standard Error of the Mean |
| 21.399 |
| 2-Sided |
| 95 |
| 339.29 |
| 423.17 |
Data were analysed with ANCOVA in log transformed data. Results were converted back to original scale. |
| Other |
| ANCOVA | Data were analysed with ANCOVA in log transformed data. | <0.001 | Least Squares Mean Difference | 102.09 | Standard Error of the Mean | 25.635 | 2-Sided | 95 | 51.84 | 152.33 | Data were analysed with ANCOVA in log transformed data. Results were converted back to original scale. | Other |
| Least Squares Mean Difference |
| 19.8 |
| 2-Sided |
| 95 |
| 13.4 |
| 26.1 |
| Other |
| ANCOVA | 0.003 | Least Squares Mean Difference | 8.5 | 2-Sided | 95 | 3.0 | 14.0 | Other |
| Least Squares Mean Difference |
| -4.5 |
| 2-Sided |
| 95 |
| -6.3 |
| -2.6 |
| Other |
| ANCOVA | 0.277 | Least Squares Mean Difference | -0.8 | 2-Sided | 95 | -2.4 | 0.7 | Other |
| Least Squares Mean Difference |
| -637.7 |
| 2-Sided |
| 95 |
| -925.2 |
| -350.2 |
| Other |
| ANCOVA | 0.006 | Least Squares Mean Difference | -341.6 | 2-Sided | 95 | -585.2 | -97.9 | Other |
| Least Squares Mean Difference |
| -309.8 |
| 2-Sided |
| 95 |
| -423.0 |
| -196.6 |
| Other |
| Mixed Models Analysis | 0.187 | Least Squares Mean Difference | -64.3 | 2-Sided | 95 | -160.3 | 31.7 | Other |