GLP-1 Peptide Atlas, by Delfa

CompletedPhase 1Results posted

A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus

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

Lead sponsor

Eli Lilly and Company

Asset

Tirzepatide

Subcutaneous · GLP-1 / GIP dual

Listed sites

Recruiting sites

—

Enrollment

actual

Study population

Type 2 diabetes

Key I/E criteria

•BMI 23-45•HbA1c 6.5-9%

Primary endpoint

•Mean Glucagon Concentration During Induced Hypoglycemia From Target Plasma

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT04050553

Org study ID17222

Secondary ID2019-001360-29

Secondary IDI8F-MC-GPHGEli Lilly and Company

Timeline

Milestones

Study first posted2019-08-08actual

Study start2020-02-24actual

Primary completion2022-01-25actual

Study completion2022-01-25actual

Last update posted2024-05-20actual

Results first posted2024-05-20actual

Assets

Investigational agents

Tirzepatide

Study populations

Who this study enrolls

Type 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

Maximum age70 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Have type 2 diabetes mellitus (T2DM) for at least 1 year

•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.

•Have a hemoglobin A1c (HbA1c) value at screening of ≥6.5% and ≤9.0 % if on metformin only.

•Have a HbA1c value at screening of ≥6.0% and ≤8.5 %, if on metformin and 1 more allowed OAM.

•Have a body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m²) inclusive, at screening

•Are of stable weight (±5%) >3 months prior to screening

Exclusion criteria

•Have a history of proliferative retinopathy or maculopathy as determined by the investigator based on a recent (<6 months) ophthalmologic examination

•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)

•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

•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])

Endpoints (14)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Glycemic / diabetes

Cardiometabolic biomarkers

Safety / tolerability / PK

Glycemic / diabetes

8 endpoints

Primary/registry result/low confidence

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

Time frame:Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

change from baseline, descriptive

Posted result

Group	Value (least_squares_mean), picomole per liter (pmol/L)	95% CI
Placebo	18.55	—
Tirzepatide 15 mg	18.07	—

Least Square (LS) Mean Difference-0.4995% CI-3.64 – 2.67p0.7556Mixed Models Analysis

Primary/protocol endpoint/low confidence

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

Time frame:Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

change from baseline, descriptive

Secondary/registry result/low confidence

Change in Mean Insulin Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL

Time frame:Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

change from baseline, descriptive

Posted result

Group	Value (least_squares_mean), picomole per liter (pmol/L)	95% CI
Placebo	-1053.31	—
Tirzepatide 15 mg	-1228.08	—

LS Mean Difference-174.7795% CI-290.34 – -59.21p0.0043Mixed Models Analysis

Secondary/registry result

Change in Mean C-peptide Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL

Time frame:Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

C-peptide AUC

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), picomole per liter (pmol/L)	95% CI
Placebo	-177.69	—
Tirzepatide 15 mg	-665.99	—

LS Mean Difference-488.3195% CI-621.25 – -355.36p<0.0001Mixed Models Analysis

Secondary/registry result/low confidence

Time From Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)

Time frame: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).

descriptive

Posted result

Group	Value (least_squares_mean), minutes (min)	95% CI
Placebo	43.34	—
Tirzepatide 15 mg	47.73	—

LS Mean Difference4.3995% CI1.69 – 7.08p0.0023Mixed Models Analysis

Secondary/protocol endpoint/low confidence

Change in Mean Insulin Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL

Time frame:Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

change from baseline, improvement

Secondary/protocol endpoint

Change in Mean C-peptide Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL

Time frame:Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

C-peptide AUC

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Time From Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)

Time frame: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).

time to event, improvement

LOINC 1558-6

Cardiometabolic biomarkers

4 endpoints

Secondary/registry result

Mean Change in Blood Pressure From Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL

Time frame:Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), millimeters of Mercury (mmHg)	95% CI
PlaceboSystolic Blood Pressure	-5.01	—
Diastolic Blood Pressure	-9.84	—
Tirzepatide 15 mgSystolic Blood Pressure	-5.51	—
Diastolic Blood Pressure	-7.88	—

LS Mean Difference-0.5195% CI-5.28 – 4.27p0.8298Mixed Models Analysis

For systolic blood pressure.

LS Mean Difference1.9695% CI-0.76 – 4.67p0.1516Mixed Models Analysis

For diastolic blood pressure.

Secondary/registry result

Mean Change in Heart Rate From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL

Time frame:Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), beats per minute (beats/min)	95% CI
Placebo	5.56	—
Tirzepatide 15 mg	4.67	—

LS Mean Difference-0.8995% CI-4.10 – 2.33p0.5776Mixed Models Analysis

Secondary/protocol endpoint

Mean Change in Blood Pressure From Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL

Time frame:Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

change from baseline, improvement

Secondary/protocol endpoint

Mean Change in Heart Rate From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL

Time frame:Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

Heart rate, change

change from baseline, improvement

Safety / tolerability / PK

2 endpoints

Secondary/registry result

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)

Time frame:Week 12.

descriptive

Posted result

Group	Value (least_squares_mean), Score on a scale	95% CI
Placebo100 mg/dL	1.19	—
63 mg/dL	1.35	—
45 mg/dL	1.68	—
72 mg/dL	1.50	—
Tirzepatide 15 mg100 mg/dL	1.13	—
63 mg/dL	1.17	—
45 mg/dL	1.49	—
72 mg/dL	1.38	—

LS Mean Difference-0.0695% CI-0.13 – 0.00p0.0505Mixed Models Analysis

For Overall Hypoglycemia Symptom Score at concentration of 100 mg/dL.

LS Mean Difference-0.1895% CI-0.31 – -0.05p0.0104Mixed Models Analysis

For Overall Hypoglycemia Symptom Score at concentration of 63 mg/dL.

LS Mean Difference-0.1995% CI-0.32 – -0.06p0.0068Mixed Models Analysis

For Overall Hypoglycemia Symptom Score at concentration of 45 mg/dL.

LS Mean Difference-0.1195% CI-0.30 – 0.08p0.2302Mixed Models Analysis

For Overall Hypoglycemia Symptom Score at concentration of 72 mg/dL.

Secondary/protocol endpoint

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)

Time frame:Week 12.

descriptive

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Counterregulatory response to hypoglycemia during a hypoglycemic clamp in people with type 2 diabetes treated with tirzepatide.
Frontiers in endocrinology2025 (year)PMID40964167doi:10.3389/fendo.2025.1627947via clinicaltrials gov reference derived + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.