Trial · Interventional

CompletedPhase 1Results postedRegistry data

A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus

NCTNCT04050553Other id17222Other idI8F-MC-GPHGOther id2019-001360-29Other id2019

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 1
Enrollment: 42 participants (actual)
Sponsor: Eli Lilly and Company · Industry
Design: Randomized · Double masking
Countries: 1 country
Austria
Start: 24 Feb 2020
Primary completion: 25 Jan 2022
Completion: 25 Jan 2022
First posted: 8 Aug 2019
Last update posted: 20 May 2024
Conditions: Diabetes Mellitus, Type 2 · Hypoglycemia

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2020202120222023

Ph 1
A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus
NCT04050553
24 Feb 2020 to 25 Jan 2022

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

TirzepatideDrug
PlaceboDrug

Arms2

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

Primary outcomes1

Outcomes the sponsor listed as 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
Time frame · Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.
Registry 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.

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

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

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

Group	Value (picomole per liter (pmol/L))	Spread
Placebo	18.55	1.64
Tirzepatide 15 mg	18.07	1.62

Secondary and other outcome results(6)

Secondary outcomeLeast squares mean· Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

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

Group	Value (picomole per liter (pmol/L))	Spread
Placebo	-1053.31	54.20
Tirzepatide 15 mg	-1228.08	53.61

Secondary outcomeLeast squares mean· 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

Group	Value (picomole per liter (pmol/L))	Spread
Placebo	-177.69	51.78
Tirzepatide 15 mg	-665.99	51.09

Secondary outcomeLeast squares mean· 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 From Termination of Insulin Infusion at PG Concentration of 45 mg/dL to Reach Recovery PG Concentration (72 mg/dL)

Group	Value (minutes (min))	Spread
Placebo	43.34	1.29
Tirzepatide 15 mg	47.73	1.27

Secondary outcomeLeast squares mean· Week 12.

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)

Group	Value (Score on a scale)	Spread
Placebo	1.19	0.03
Tirzepatide 15 mg	1.13	0.03

Secondary outcomeLeast squares mean· Week 12 in each study period: Baseline and up to 30 minutes after reaching the nadir glucose level.

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

Group	Value (millimeters of Mercury (mmHg))	Spread
Placebo	-5.01	2.22
Tirzepatide 15 mg	-5.51	2.17

Secondary outcomeLeast squares mean· 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

Group	Value (beats per minute (beats/min))	Spread
Placebo	5.56	1.26
Tirzepatide 15 mg	4.67	1.23

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
PlaceboParticipants received placebo administered SC QW for 12 weeks.	0 / 36	0 / 36	13 / 36
Tirzepatide 15 mgParticipants 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

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2025

10 results

Counterregulatory response to hypoglycemia during a hypoglycemic clamp in people with type 2 diabetes treated with tirzepatide.

Pieber et al. 2025Frontiers in endocrinologycited by 2

PMID 40964167PMC12436105DOI 10.3389/fendo.2025.1627947PUB-40964167

CC BY10 results

Download PDF See results (10)

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years up to 70 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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 \[including transient ischemic attack\])

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