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| ID | Type | Description | Link |
|---|---|---|---|
| I8F-MC-GPHG | Other Identifier | Eli Lilly and Company | |
| 2019-001360-29 | EudraCT Number |
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The main purpose of this study is to learn more about how tirzepatide affects the body's response to low blood sugar (hypoglycemia). The study is open to participants with type 2 diabetes. It will last about 42 weeks for each participant.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tirzepatide | Experimental | Participants received a starting dose of 2.5 mg tirzepatide once weekly (QW) for 2 weeks, followed by an increase to 5 mg QW for 2 weeks, and 10 mg QW for 4 weeks until the 15-mg dose was reached and maintained for the remainder of the treatment period (4 weeks) administered subcutaneously (SC) in one of two study periods. |
|
| Placebo | Placebo Comparator | Participants received placebo QW administered SC in one of two study periods. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tirzepatide | Drug | Administered SC |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mean Glucagon Concentration During Induced Hypoglycemia From Target Plasma Glucose (PG) Concentration of 100 Milligrams Per Deciliter (mg/dL) to a Nadir Target of 45 mg/dL | A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using restricted maximum likelihood (REML) method was used. PG of plateau 100 mg/dL was considered as baseline timepoint. | Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mean Insulin Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL | A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used. | Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level. |
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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 |
|---|---|---|---|---|---|---|
| Universitätsklinikum Graz | Graz | Styria | 8036 | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40964167 | Derived | Pieber TR, Svehlikova E, Urva S, Haupt A, Zhou C, Coskun T, Holler V, Fluhr G, Karanikas CA, Milicevic Z, Pratt EJ. Counterregulatory response to hypoglycemia during a hypoglycemic clamp in people with type 2 diabetes treated with tirzepatide. Front Endocrinol (Lausanne). 2025 Sep 2;16:1627947. doi: 10.3389/fendo.2025.1627947. eCollection 2025. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo/Tirzepatide 15 Milligrams (mg) | Period 1: Participants received placebo administered subcutaneously (SC) once-weekly (QW) for 12 weeks; Wash-out: 8-10 weeks; Period 2: Participants received a starting dose of 2.5 mg tirzepatide given SC QW for 2 weeks, followed by an increase to 5 mg QW for 2 weeks, and 10 mg QW for 4 weeks until the 15-mg dose was reached and maintained for the remainder of the treatment period (4 weeks). |
| FG001 | Tirzepatide 15 mg/Placebo | Period 1: Participants received a starting dose of 2.5 mg tirzepatide given SC QW for 2 weeks, followed by an increase to 5 mg QW for 2 weeks, and 10 mg QW for 4 weeks until the 15-mg dose was reached and maintained for the remainder of the treatment period (4 weeks); Wash-out: 8-10 weeks; Period 2: Participants received placebo administered SC QW for 12 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
|
| ||||||||||||||||||||||||
| Wash-out |
| |||||||||||||||||||||||||
| Period 2 |
|
All randomized participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo/Tirzepatide 15 mg | Period 1: Participants received placebo administered SC QW for 12 weeks; Wash-out: 8-10 weeks; Period 2: Participants received a starting dose of 2.5 mg tirzepatide given SC QW for 2 weeks, followed by an increase to 5 mg QW for 2 weeks, and 10 mg QW for 4 weeks until the 15-mg dose was reached and maintained for the remainder of the treatment period (4 weeks). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 in Mean Glucagon Concentration During Induced Hypoglycemia From Target Plasma Glucose (PG) Concentration of 100 Milligrams Per Deciliter (mg/dL) to a Nadir Target of 45 mg/dL | A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using restricted maximum likelihood (REML) method was used. PG of plateau 100 mg/dL was considered as baseline timepoint. | All participants who received at least one dose of study drug and had evaluable Pharmacodynamic (PD) data for this outcome. | Posted | Least Squares Mean | Standard Error | picomole per liter (pmol/L) | Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level. |
|
Baseline Through End of Safety Follow-Up (Up To 36 Weeks)
All participants who received at least one dose of study drug. Per protocol, Adverse Event analysis was planned as per treatment regimen received.
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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 QW for 12 weeks. | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Obstructive pancreatitis | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA 22.1 | 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 | Sep 17, 2020 | Jan 9, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 26, 2021 | Jan 9, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D007003 | Hypoglycemia |
| 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 |
| 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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| Placebo | Drug | Administered SC |
|
| Change in Mean C-peptide Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL | A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used. | Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level. |
| Time From Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL) | A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used. | Week 12 in each treatment period (treatment period = 12 weeks): 1 minute after reaching the nadir glucose level and when reaching normoglycemia (estimated as 30 mins). |
| Hypoglycemia Symptoms Score From Induced Hypoglycemia at Target PG Concentrations of 100 mg/dL, 63 mg/dL, 45 mg/dL and Recovery (PG Concentration 72 mg/dL) | Hypoglycemia symptoms score was measured with the Edinburgh Hypoglycemia Symptom Scale (EHSS) which is a 13-item questionnaire for hypoglycemic symptoms: 10 neuroglycopenic symptoms (6 cognitive dysfunctions: inability to concentrate, blurred vision, anxiety, confusion, difficulty speaking, and double vision; 4 neuroglycopenia: drowsiness, tiredness, hunger, and weakness), and 3 autonomic symptoms (sweating, trembling, and warmness) and participants were asked to rate the intensity of their hypoglycemic symptoms on a 7-point Likert scale (1 = No symptom to 7 = Severe). The total score is the sum of scores from the 13 questions and ranged from 13 to 91. This score was scaled back to the range of 1 to 7 by taking average of the sum of scores (i.e., sum of the scores divided by number of questions), where lower score indicates fewer symptoms. | Week 12. |
| Mean Change in Blood Pressure From Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL | A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used. | Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level. |
| Mean Change in Heart Rate From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL | A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used. | Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level. |
| Withdrawal by Subject |
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| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| BG001 | Tirzepatide 15 mg/Placebo | Period 1: Participants received a starting dose of 2.5 mg tirzepatide given SC QW for 2 weeks, followed by an increase to 5 mg QW for 2 weeks, and 10 mg QW for 4 weeks until the 15-mg dose was reached and maintained for the remainder of the treatment period (4 weeks); Wash-out: 8-10 weeks; Period 2: Participants received placebo administered SC QW for 12 weeks. |
| BG002 | Total | Total of all reporting groups |
| 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 | No |
|
| OG001 | Tirzepatide 15 mg | Participants received a starting dose of 2.5 mg tirzepatide given SC QW for 2 weeks, followed by an increase to 5 mg QW for 2 weeks, and 10 mg QW for 4 weeks until the 15-mg dose was reached and maintained for the remainder of the treatment period (4 weeks). |
|
|
|
| Secondary | Change in Mean Insulin Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL | A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used. | All participants who received at least one dose of study drug and had evaluable PD data for this outcome. | Posted | Least Squares Mean | Standard Error | picomole per liter (pmol/L) | Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level. |
|
|
|
|
| Secondary | Change in Mean C-peptide Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL | A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used. | All participants who received at least one dose of study drug and had evaluable PD data for this outcome. | Posted | Least Squares Mean | Standard Error | picomole per liter (pmol/L) | Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level. |
|
|
|
|
| Secondary | Time From Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL) | A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used. | All participants who received at least one dose of study drug and had evaluable PD data for this outcome. | Posted | Least Squares Mean | Standard Error | minutes (min) | Week 12 in each treatment period (treatment period = 12 weeks): 1 minute after reaching the nadir glucose level and when reaching normoglycemia (estimated as 30 mins). |
|
|
|
|
| Secondary | Hypoglycemia Symptoms Score From Induced Hypoglycemia at Target PG Concentrations of 100 mg/dL, 63 mg/dL, 45 mg/dL and Recovery (PG Concentration 72 mg/dL) | Hypoglycemia symptoms score was measured with the Edinburgh Hypoglycemia Symptom Scale (EHSS) which is a 13-item questionnaire for hypoglycemic symptoms: 10 neuroglycopenic symptoms (6 cognitive dysfunctions: inability to concentrate, blurred vision, anxiety, confusion, difficulty speaking, and double vision; 4 neuroglycopenia: drowsiness, tiredness, hunger, and weakness), and 3 autonomic symptoms (sweating, trembling, and warmness) and participants were asked to rate the intensity of their hypoglycemic symptoms on a 7-point Likert scale (1 = No symptom to 7 = Severe). The total score is the sum of scores from the 13 questions and ranged from 13 to 91. This score was scaled back to the range of 1 to 7 by taking average of the sum of scores (i.e., sum of the scores divided by number of questions), where lower score indicates fewer symptoms. | All participants who received at least one dose of study drug and had evaluable PD data for this outcome. | Posted | Least Squares Mean | Standard Error | Score on a scale | Week 12. |
|
|
|
|
| Secondary | Mean Change in Blood Pressure From Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL | A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used. | All participants who received at least one dose of study drug and had evaluable PD data for this outcome. | Posted | Least Squares Mean | Standard Error | millimeters of Mercury (mmHg) | Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level. |
|
|
|
|
| Secondary | Mean Change in Heart Rate From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL | A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using REML method was used. | All participants who received at least one dose of study drug and had evaluable PD data for this outcome. | Posted | Least Squares Mean | Standard Error | beats per minute (beats/min) | Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level. |
|
|
|
|
| 36 |
| 0 |
| 36 |
| 13 |
| 36 |
| EG001 | Tirzepatide 15 mg | Participants received a starting dose of 2.5 mg tirzepatide given SC QW for 2 weeks, followed by an increase to 5 mg QW for 2 weeks, and 10 mg QW for 4 weeks until the 15-mg dose was reached and maintained for the remainder of the treatment period (4 weeks). | 0 | 39 | 4 | 39 | 27 | 39 |
| Scrotal abscess | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Facial paralysis | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Injection site reaction | General disorders | MedDRA 22.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Pancreatic enzymes increased | Investigations | MedDRA 22.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA 22.1 | 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 |
| 63 mg/dL |
|
|
| 45 mg/dL |
|
|
| 72 mg/dL |
|
|
| Mixed Models Analysis |
| 0.0104 |
| LS Mean Difference |
| -0.18 |
| 2-Sided |
| 95 |
| -0.31 |
| -0.05 |
| Superiority |
| For Overall Hypoglycemia Symptom Score at concentration of 45 mg/dL. | Mixed Models Analysis | 0.0068 | LS Mean Difference | -0.19 | 2-Sided | 95 | -0.32 | -0.06 | Superiority |
| For Overall Hypoglycemia Symptom Score at concentration of 72 mg/dL. | Mixed Models Analysis | 0.2302 | LS Mean Difference | -0.11 | 2-Sided | 95 | -0.30 | 0.08 | Superiority |
| 0.1516 |
| LS Mean Difference |
| 1.96 |
| 2-Sided |
| 95 |
| -0.76 |
| 4.67 |
| Superiority |