ClinicalTrials.gg
Sign In
CompletedNCT04050553Updated May 20, 2024Results posted

A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus

A Phase 1 interventional study of Tirzepatide and Placebo in Diabetes Mellitus, Type 2 and Hypoglycemia, sponsored by Eli Lilly and Company. Completed at 1 site in Austria. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2024-05-20.

Sponsored by Eli Lilly and Company · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
42
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Diabetes Mellitus, Type 2
  • Hypoglycemia
03

In context

Diabetes Mellitus, Type 2

9,589 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,332 are open to participants now.

This study's enrollment of 42 is below the median of 81 across 7,713 interventional studies indexed under Diabetes Mellitus, Type 2.

Browse Diabetes Mellitus, Type 2 studies →

Lead sponsor

Eli Lilly and Company is the lead sponsor of 2,095 studies on the registry; 142 are open to participants now.

Of its 535 completed or terminated interventional studies of FDA-regulated products, 356 (67%) have results posted.

Browse Eli Lilly and Company studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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])
05

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
42 participants (actual)

Study arms

  • Experimental
    Tirzepatide

    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.

    Drug: Tirzepatide

  • Placebo comparator
    Placebo

    Participants received placebo QW administered SC in one of two study periods.

    Drug: Placebo

Interventions

  • DrugTirzepatide

    Administered SC

    Also known as: LY3298176

  • DrugPlacebo

    Administered SC

06

What researchers measure

Primary outcomes

  1. 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.

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

Secondary outcomes

  1. 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.

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

  2. 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.

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

  3. 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.

    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).

  4. 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.

    Time frame: Week 12.

  5. 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.

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

  6. 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.

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

07

Results

Posted May 20, 2024

Participant flow

Period 1
Participant flow — Period 1
MilestonePlacebo/Tirzepatide 15 Milligrams (mg)Tirzepatide 15 mg/Placebo
Started2121
Received at least one dose of study drug2121
Completed1817
Not completed34
Withdrew: Physician decision22
Withdrew: Adverse event11
Withdrew: Withdrawal by subject01
Wash-out
Participant flow — Wash-out
MilestonePlacebo/Tirzepatide 15 Milligrams (mg)Tirzepatide 15 mg/Placebo
Started1817
Completed1815
Not completed02
Withdrew: Adverse event01
Withdrew: Withdrawal by subject01
Period 2
Participant flow — Period 2
MilestonePlacebo/Tirzepatide 15 Milligrams (mg)Tirzepatide 15 mg/Placebo
Started1815
Received at least one dose of study drug1815
Completed1815
Not completed00

Outcome measures

PrimaryChange 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.

Time frame:
Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
Reported as:
Least squares mean · picomole per liter (pmol/L)
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
picomole per liter (pmol/L)PlaceboTirzepatide 15 mg
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/dL18.55 ± 1.6418.07 ± 1.62
Statistical analysis
  • Placebo vs Tirzepatide 15 mg · Mixed Models Analysis · p = 0.7556 · Least square (ls) mean difference: -0.49 · 95% CI -3.64 to 2.67
SecondaryChange 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.

Time frame:
Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
Reported as:
Least squares mean · picomole per liter (pmol/L)
Change in Mean Insulin Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
picomole per liter (pmol/L)PlaceboTirzepatide 15 mg
Change in Mean Insulin Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL-1053.31 ± 54.20-1228.08 ± 53.61
Statistical analysis
  • Placebo vs Tirzepatide 15 mg · Mixed Models Analysis · p = 0.0043 · Ls mean difference: -174.77 · 95% CI -290.34 to -59.21
SecondaryChange 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.

Time frame:
Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
Reported as:
Least squares mean · picomole per liter (pmol/L)
Change in Mean C-peptide Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
picomole per liter (pmol/L)PlaceboTirzepatide 15 mg
Change in Mean C-peptide Concentrations From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL-177.69 ± 51.78-665.99 ± 51.09
Statistical analysis
  • Placebo vs Tirzepatide 15 mg · Mixed Models Analysis · p = <0.0001 · Ls mean difference: -488.31 · 95% CI -621.25 to -355.36
SecondaryTime 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.

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).
Reported as:
Least squares mean · minutes (min)
Time From Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)
minutes (min)PlaceboTirzepatide 15 mg
Time From Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)43.34 ± 1.2947.73 ± 1.27
Statistical analysis
  • Placebo vs Tirzepatide 15 mg · Mixed Models Analysis · p = 0.0023 · Ls mean difference: 4.39 · 95% CI 1.69 to 7.08
SecondaryHypoglycemia 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.

Time frame:
Week 12.
Reported as:
Least squares mean · Score on a scale
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)
Score on a scalePlaceboTirzepatide 15 mg
100 mg/dL1.19 ± 0.031.13 ± 0.03
63 mg/dL1.35 ± 0.061.17 ± 0.06
45 mg/dL1.68 ± 0.081.49 ± 0.08
72 mg/dL1.50 ± 0.091.38 ± 0.09
Statistical analysis
  • Placebo vs Tirzepatide 15 mg · Mixed Models Analysis · p = 0.0505 · Ls mean difference: -0.06 · 95% CI -0.13 to 0.00
  • Placebo vs Tirzepatide 15 mg · Mixed Models Analysis · p = 0.0104 · Ls mean difference: -0.18 · 95% CI -0.31 to -0.05
  • Placebo vs Tirzepatide 15 mg · Mixed Models Analysis · p = 0.0068 · Ls mean difference: -0.19 · 95% CI -0.32 to -0.06
  • Placebo vs Tirzepatide 15 mg · Mixed Models Analysis · p = 0.2302 · Ls mean difference: -0.11 · 95% CI -0.30 to 0.08
SecondaryMean 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.

Time frame:
Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
Reported as:
Least squares mean · millimeters of Mercury (mmHg)
Mean Change in Blood Pressure From Induced Hypoglycemia Target PG Nadir Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
millimeters of Mercury (mmHg)PlaceboTirzepatide 15 mg
Systolic Blood Pressure-5.01 ± 2.22-5.51 ± 2.17
Diastolic Blood Pressure-9.84 ± 1.16-7.88 ± 1.13
Statistical analysis
  • Placebo vs Tirzepatide 15 mg · Mixed Models Analysis · p = 0.8298 · Ls mean difference: -0.51 · 95% CI -5.28 to 4.27
  • Placebo vs Tirzepatide 15 mg · Mixed Models Analysis · p = 0.1516 · Ls mean difference: 1.96 · 95% CI -0.76 to 4.67
SecondaryMean 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.

Time frame:
Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
Reported as:
Least squares mean · beats per minute (beats/min)
Mean Change in Heart Rate From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL
beats per minute (beats/min)PlaceboTirzepatide 15 mg
Mean Change in Heart Rate From Induced Hypoglycemia Target PG Concentration of 100 mg/dL to a Nadir Target of 45 mg/dL5.56 ± 1.264.67 ± 1.23
Statistical analysis
  • Placebo vs Tirzepatide 15 mg · Mixed Models Analysis · p = 0.5776 · Ls mean difference: -0.89 · 95% CI -4.10 to 2.33

Adverse events

Collected over Baseline Through End of Safety Follow-Up (Up To 36 Weeks). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/36 (0%)0/36 (0%)13/36 (36.1%)
Tirzepatide 15 mg0/39 (0%)4/39 (10.3%)27/39 (69.2%)
Most frequent serious events
Most frequent serious events
EventPlaceboTirzepatide 15 mg
Obstructive pancreatitisGastrointestinal disorders0/361/39
Scrotal abscessInfections and infestations0/361/39
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders0/361/39
Facial paralysisNervous system disorders0/361/39
Most frequent other events
Showing 10 of 19
Most frequent other events
EventPlaceboTirzepatide 15 mg
NauseaGastrointestinal disorders2/3615/39
DiarrhoeaGastrointestinal disorders4/367/39
HeadacheNervous system disorders3/367/39
DyspepsiaGastrointestinal disorders0/366/39
VomitingGastrointestinal disorders1/366/39
Decreased appetiteMetabolism and nutrition disorders0/366/39
Abdominal distensionGastrointestinal disorders1/365/39
VertigoEar and labyrinth disorders3/364/39
Abdominal pain upperGastrointestinal disorders0/364/39
EructationGastrointestinal disorders0/364/39

Baseline characteristics

All randomized participants.

Age, Continuous
Age, Continuous(years)Placebo/Tirzepatide 15 mgTirzepatide 15 mg/PlaceboTotal
Mean58.9 ± 4.855.4 ± 7.457.1 ± 6.4
Sex: Female, Male
Sex: Female, Male(Participants)Placebo/Tirzepatide 15 mgTirzepatide 15 mg/PlaceboTotal
Female279
Male191433
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Placebo/Tirzepatide 15 mgTirzepatide 15 mg/PlaceboTotal
Hispanic or Latino000
Not Hispanic or Latino212142
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Placebo/Tirzepatide 15 mgTirzepatide 15 mg/PlaceboTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White212142
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(Participants)Placebo/Tirzepatide 15 mgTirzepatide 15 mg/PlaceboTotal
Austria212142
08

Study locations

1 site
  • Universitätsklinikum Graz
    Graz, Styria 8036, Austria
09

References and documents

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 documents

  • Study protocol · Sep 17, 2020
  • Statistical analysis plan · Oct 26, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Feb 2020 to primary completion in Jan 2022, 23 months.

Results were first posted in May 2024, 2 years 3 months after primary completion.

Of 393 industry-sponsored phase 1 interventional studies under Diabetes Mellitus, Type 2, half reached primary completion within 6 months of starting (the median), counting those still running; a quarter within 2 and three quarters within 12. This study's 23 months is above that.

Counting every sponsor, half of 458 studies reached it within 7 months; a quarter within 2 and three quarters within 14.

How these figures are worked out, and which studies are left out of them.

Registered
Aug 7, 2019
First posted
Aug 8, 2019
StartActual
Feb 24, 2020
Primary completionActual
Jan 25, 2022
CompletionActual
Jan 25, 2022
Results first posted
May 20, 2024
Last update
May 20, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on May 20, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04050553
Lead sponsor
Eli Lilly and Company
Responsible party
Sponsor
First posted
Aug 8, 2019
Start date
Feb 24, 2020
Primary completion
Jan 25, 2022
Completion
Jan 25, 2022
Results posted
May 20, 2024
Last update
May 20, 2024

Study contacts

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

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Dec 2023. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Tirzepatide

Other studies in this condition

Diabetes Mellitus, Type 2 →

Other studies from this sponsor

Eli Lilly and Company →

Start the discussion