Diabetes Mellitus, Type 2Phase 1NCT04050553
A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus
A Phase 1 study testing Tirzepatide in people with Diabetes Mellitus, Type 2 and Hypoglycemia, run by Eli Lilly and Company at 1 site in Austria.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diabetes Mellitus, Type 2, Hypoglycemia
- What is being tested?
- Tirzepatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteAustria
- Study dates
- 24 Feb 2020to 25 Jan 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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])
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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.
- Conditions
- Diabetes Mellitus, Type 2, Hypoglycemia
- Being tested
- Tirzepatide, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
Also called LY3298176
Administered SC
PlaceboDrug
Administered SC
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Tirzepatide |
| Placebo | Placebo comparator | Participants received placebo QW administered SC in one of two study periods. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
Secondary outcomes (6)
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.
Measured: Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2019
- Study start24 Feb 2020
- Primary completion25 Jan 2022
- Study completion25 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04050553
- Sponsor's protocol ID
- 17222
- Other IDs
- I8F-MC-GPHG, 2019-001360-29, 2019
- Status last verified
- Dec 2023
- First submitted
- 7 Aug 2019
- Last updated
- 20 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40964167
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04050553
- Acronym / sponsor ID
- 17222
- Conditions
- Diabetes Mellitus, Type 2, Hypoglycemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 24 Feb 2020 (actual)
- Primary completion
- 25 Jan 2022 (actual)
- Study completion
- 25 Jan 2022 (actual)
- First posted
- 8 Aug 2019 (actual)
- Results
- Posted 20 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tirzepatide | Experimental | Drug: TirzepatideParticipants 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 | Drug: PlaceboParticipants received placebo QW administered SC in one of two study periods. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- 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])
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TirzepatideAlso: LY3298176Administered SC | Drug | Tirzepatide |
| PlaceboAdministered SC | Drug | Placebo |
Primary outcome
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.
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.
6 secondary outcomes
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 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.
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).
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40964167Pieber 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tirzepatide in people with Diabetes Mellitus, Type 2 and Hypoglycemia, run by Eli Lilly and Company at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04050553, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2024.