{"protocolSection":{"identificationModule":{"nctId":"NCT04050553","orgStudyIdInfo":{"id":"17222"},"secondaryIdInfos":[{"id":"I8F-MC-GPHG","type":"OTHER","domain":"Eli Lilly and Company"},{"id":"2019-001360-29","type":"EUDRACT_NUMBER"},{"id":"2019","type":"NIH","link":"https://reporter.nih.gov/quickSearch/2019"}],"organization":{"fullName":"Eli Lilly and Company","class":"INDUSTRY"},"briefTitle":"A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus","officialTitle":"A Randomized, Placebo-Controlled, Crossover Study to Investigate the Effect of Once-Weekly Tirzepatide on the Counter-Regulatory Response to Hypoglycemia in Patients With Type 2 Diabetes Mellitus"},"statusModule":{"statusVerifiedDate":"2023-12","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2020-02-24","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2022-01-25","type":"ACTUAL"},"completionDateStruct":{"date":"2022-01-25","type":"ACTUAL"},"studyFirstSubmitDate":"2019-08-07","studyFirstSubmitQcDate":"2019-08-07","studyFirstPostDateStruct":{"date":"2019-08-08","type":"ACTUAL"},"resultsFirstSubmitDate":"2023-01-24","resultsFirstSubmitQcDate":"2023-12-07","resultsFirstPostDateStruct":{"date":"2024-05-20","type":"ACTUAL"},"lastUpdateSubmitDate":"2023-12-07","lastUpdatePostDateStruct":{"date":"2024-05-20","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"Eli Lilly and Company","class":"INDUSTRY"}},"oversightModule":{"oversightHasDmc":false,"isFdaRegulatedDrug":true,"isFdaRegulatedDevice":false,"isUsExport":true},"descriptionModule":{"briefSummary":"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."},"conditionsModule":{"conditions":["Diabetes Mellitus, Type 2","Hypoglycemia"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE1"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"CROSSOVER","primaryPurpose":"BASIC_SCIENCE","maskingInfo":{"masking":"DOUBLE","whoMasked":["PARTICIPANT","INVESTIGATOR"]}},"enrollmentInfo":{"count":42,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Tirzepatide","type":"EXPERIMENTAL","description":"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.","interventionNames":["Drug: Tirzepatide"]},{"label":"Placebo","type":"PLACEBO_COMPARATOR","description":"Participants received placebo QW administered SC in one of two study periods.","interventionNames":["Drug: Placebo"]}],"interventions":[{"type":"DRUG","name":"Tirzepatide","description":"Administered SC","armGroupLabels":["Tirzepatide"],"otherNames":["LY3298176"]},{"type":"DRUG","name":"Placebo","description":"Administered SC","armGroupLabels":["Placebo"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"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","description":"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.","timeFrame":"Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level."}],"secondaryOutcomes":[{"measure":"Change in Mean Insulin Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL","description":"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.","timeFrame":"Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level."},{"measure":"Change in Mean C-peptide Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL","description":"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.","timeFrame":"Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level."},{"measure":"Time From Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)","description":"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.","timeFrame":"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)."},{"measure":"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)","description":"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.","timeFrame":"Week 12."},{"measure":"Mean Change in Blood Pressure From Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL","description":"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.","timeFrame":"Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level."},{"measure":"Mean Change in Heart Rate From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL","description":"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.","timeFrame":"Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level."}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Have type 2 diabetes mellitus (T2DM) for at least 1 year\n* Treated with diet and exercise and stable dose(s) of metformin 3 months prior to study entry with or without 1 additional oral antidiabetic medication (OAM) other than metformin.\n* Have a hemoglobin A1c (HbA1c) value at screening of ≥6.5% and ≤9.0 % if on metformin only.\n* Have a HbA1c value at screening of ≥6.0% and ≤8.5 %, if on metformin and 1 more allowed OAM.\n* Have a body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m²) inclusive, at screening\n* Are of stable weight (±5%) \\>3 months prior to screening\n\nExclusion Criteria:\n\n* Have a history of proliferative retinopathy or maculopathy as determined by the investigator based on a recent (\\<6 months) ophthalmologic examination\n* Impaired renal estimated glomerular filtration rate (eGFR) \\<60 milliliters per minute per 1.73 square meters (mL/min/1.73 m²) calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)\n* Have a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological or neurological disorders capable of significantly altering the absorption, metabolism or elimination of drugs; of constituting a risk when taking the study drug; or of interfering with the interpretation of data\n* Have had acute myocardial infarction, congestive heart failure New York Heart Association Class III or IV, history of or suspected ischemic heart disease, and/or cerebrovascular accident (stroke \\[including transient ischemic attack\\])","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","maximumAge":"70 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"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)","affiliation":"Eli Lilly and Company","role":"STUDY_DIRECTOR"}],"locations":[{"facility":"Universitätsklinikum Graz","city":"Graz","state":"Styria","zip":"8036","country":"Austria","geoPoint":{"lat":47.06733,"lon":15.44197}}]},"referencesModule":{"references":[{"pmid":"40964167","type":"DERIVED","citation":"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."}]},"ipdSharingStatementModule":{"ipdSharing":"NO"}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Placebo/Tirzepatide 15 Milligrams (mg)","description":"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)."},{"id":"FG001","title":"Tirzepatide 15 mg/Placebo","description":"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."}],"periods":[{"title":"Period 1","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"21"},{"groupId":"FG001","numSubjects":"21"}]},{"type":"Received At Least One Dose of Study Drug","achievements":[{"groupId":"FG000","numSubjects":"21"},{"groupId":"FG001","numSubjects":"21"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"18"},{"groupId":"FG001","numSubjects":"17"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"4"}]}],"dropWithdraws":[{"type":"Physician Decision","reasons":[{"groupId":"FG000","numSubjects":"2"},{"groupId":"FG001","numSubjects":"2"}]},{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"1"},{"groupId":"FG001","numSubjects":"1"}]},{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"1"}]}]},{"title":"Wash-out","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"18"},{"groupId":"FG001","numSubjects":"17"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"18"},{"groupId":"FG001","numSubjects":"15"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"2"}]}],"dropWithdraws":[{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"1"}]},{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"1"}]}]},{"title":"Period 2","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"18"},{"groupId":"FG001","numSubjects":"15"}]},{"type":"Received At Least One Dose of Study Drug","achievements":[{"groupId":"FG000","numSubjects":"18"},{"groupId":"FG001","numSubjects":"15"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"18"},{"groupId":"FG001","numSubjects":"15"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"}]}]}]},"baselineCharacteristicsModule":{"populationDescription":"All randomized participants.","groups":[{"id":"BG000","title":"Placebo/Tirzepatide 15 mg","description":"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)."},{"id":"BG001","title":"Tirzepatide 15 mg/Placebo","description":"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."},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"21"},{"groupId":"BG001","value":"21"},{"groupId":"BG002","value":"42"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"58.9","spread":"4.8"},{"groupId":"BG001","value":"55.4","spread":"7.4"},{"groupId":"BG002","value":"57.1","spread":"6.4"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","calculatePct":false,"classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"2"},{"groupId":"BG001","value":"7"},{"groupId":"BG002","value":"9"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"19"},{"groupId":"BG001","value":"14"},{"groupId":"BG002","value":"33"}]}]}]},{"title":"Ethnicity (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","calculatePct":false,"classes":[{"categories":[{"title":"Hispanic or Latino","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Not Hispanic or Latino","measurements":[{"groupId":"BG000","value":"21"},{"groupId":"BG001","value":"21"},{"groupId":"BG002","value":"42"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}]}]},{"title":"Race (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","calculatePct":false,"classes":[{"categories":[{"title":"American Indian or Alaska Native","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Asian","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Native Hawaiian or Other Pacific Islander","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Black or African American","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"White","measurements":[{"groupId":"BG000","value":"21"},{"groupId":"BG001","value":"21"},{"groupId":"BG002","value":"42"}]},{"title":"More than one race","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}]}]},{"title":"Region of Enrollment","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","calculatePct":false,"classes":[{"title":"Austria","categories":[{"measurements":[{"groupId":"BG000","value":"21"},{"groupId":"BG001","value":"21"},{"groupId":"BG002","value":"42"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"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","description":"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.","populationDescription":"All participants who received at least one dose of study drug and had evaluable Pharmacodynamic (PD) data for this outcome.","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"picomole per liter (pmol/L)","timeFrame":"Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.","groups":[{"id":"OG000","title":"Placebo","description":"Participants received placebo administered SC QW for 12 weeks."},{"id":"OG001","title":"Tirzepatide 15 mg","description":"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)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"32"},{"groupId":"OG001","value":"33"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"18.55","spread":"1.64"},{"groupId":"OG001","value":"18.07","spread":"1.62"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY","pValue":"0.7556","statisticalMethod":"Mixed Models Analysis","paramType":"Least Square (LS) Mean Difference","paramValue":"-0.49","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-3.64","ciUpperLimit":"2.67"}]},{"type":"SECONDARY","title":"Change in Mean Insulin Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL","description":"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.","populationDescription":"All participants who received at least one dose of study drug and had evaluable PD data for this outcome.","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"picomole per liter (pmol/L)","timeFrame":"Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.","groups":[{"id":"OG000","title":"Placebo","description":"Participants received placebo administered SC QW for 12 weeks."},{"id":"OG001","title":"Tirzepatide 15 mg","description":"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)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"32"},{"groupId":"OG001","value":"33"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-1053.31","spread":"54.20"},{"groupId":"OG001","value":"-1228.08","spread":"53.61"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY","pValue":"0.0043","statisticalMethod":"Mixed Models Analysis","paramType":"LS Mean Difference","paramValue":"-174.77","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-290.34","ciUpperLimit":"-59.21"}]},{"type":"SECONDARY","title":"Change in Mean C-peptide Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL","description":"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.","populationDescription":"All participants who received at least one dose of study drug and had evaluable PD data for this outcome.","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"picomole per liter (pmol/L)","timeFrame":"Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.","groups":[{"id":"OG000","title":"Placebo","description":"Participants received placebo administered SC QW for 12 weeks."},{"id":"OG001","title":"Tirzepatide 15 mg","description":"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)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"32"},{"groupId":"OG001","value":"33"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-177.69","spread":"51.78"},{"groupId":"OG001","value":"-665.99","spread":"51.09"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY","pValue":"<0.0001","statisticalMethod":"Mixed Models Analysis","paramType":"LS Mean Difference","paramValue":"-488.31","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-621.25","ciUpperLimit":"-355.36"}]},{"type":"SECONDARY","title":"Time From Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)","description":"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.","populationDescription":"All participants who received at least one dose of study drug and had evaluable PD data for this outcome.","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"minutes (min)","timeFrame":"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).","groups":[{"id":"OG000","title":"Placebo","description":"Participants received placebo administered SC QW for 12 weeks."},{"id":"OG001","title":"Tirzepatide 15 mg","description":"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)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"31"},{"groupId":"OG001","value":"32"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"43.34","spread":"1.29"},{"groupId":"OG001","value":"47.73","spread":"1.27"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY","pValue":"0.0023","statisticalMethod":"Mixed Models Analysis","paramType":"LS Mean Difference","paramValue":"4.39","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"1.69","ciUpperLimit":"7.08"}]},{"type":"SECONDARY","title":"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)","description":"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.","populationDescription":"All participants who received at least one dose of study drug and had evaluable PD data for this outcome.","reportingStatus":"POSTED","paramType":"LEAST_SQUARES_MEAN","dispersionType":"Standard Error","unitOfMeasure":"Score on a scale","timeFrame":"Week 12.","groups":[{"id":"OG000","title":"Placebo","description":"Participants received placebo administered SC QW for 12 weeks."},{"id":"OG001","title":"Tirzepatide 15 mg","description":"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)."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"33"},{"groupId":"OG001","value":"33"}]}],"classes":[{"title":"100 mg/dL","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"33"},{"groupId":"OG001","value":"33"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1.19","spread":"0.03"},{"groupId":"OG001","value":"1.13","spread":"0.03"}]}]},{"title":"63 mg/dL","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"33"},{"groupId":"OG001","value":"33"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1.35","spread":"0.06"},{"groupId":"OG001","value":"1.17","spread":"0.06"}]}]},{"title":"45 mg/dL","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"31"},{"groupId":"OG001","value":"33"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1.68","spread":"0.08"},{"groupId":"OG001","value":"1.49","spread":"0.08"}]}]},{"title":"72 mg/dL","denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"33"},{"groupId":"OG001","value":"33"}]}],"categories":[{"measurements":[{"groupId":"OG000","value":"1.50","spread":"0.09"},{"groupId":"OG001","value":"1.38","spread":"0.09"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"groupDescription":"For Overall Hypoglycemia Symptom Score at concentration of 100 mg/dL.","nonInferiorityType":"SUPERIORITY","pValue":"0.0505","statisticalMethod":"Mixed Models Analysis","paramType":"LS Mean Difference","paramValue":"-0.06","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-0.13","ciUpperLimit":"0.00"},{"groupIds":["OG000","OG001"],"groupDescription":"For Overall Hypoglycemia Symptom Score at concentration of 63 mg/dL.","nonInferiorityType":"SUPERIORITY","pValue":"0.0104","statisticalMethod":"Mixed Models Analysis","paramType":"LS Mean 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