Diabetes Mellitus, Type 2Phase 1NCT03951753

A Study of Tirzepatide in Participants With Type 2 Diabetes Mellitus (T2DM)

A Phase 1 study testing Tirzepatide and Semaglutide in people with Diabetes Mellitus, Type 2, run by Eli Lilly and Company at 2 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This is a study for participants with type 2 diabetes mellitus. The main purpose of this study is to learn more about how tirzepatide, semaglutide and placebo affect the body's ability to respond to blood sugar levels after a meal. The study will last up to 40 weeks, including a 28-week treatment period. Read more about this study

Who is it for?: Ages 20 to 74 years
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: Tirzepatide and Semaglutide
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 117 participants
Where: 2 sitesGermany
Study dates: 28 Jun 2019to 8 Apr 2021
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 20 to 74 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Have T2DM for at least 6 months
Treated with diet and exercise and stable dose(s) of metformin, with or without 1 additional stable dose of oral antihyperglycemia medication other than metformin, 3 months prior to study entry
Have a hemoglobin A1c (HbA1c) value at screening of ≥7% and ≤ 9.5 % if on metformin only; or ≥6.5% and ≤9.0% if on metformin in combination with oral antihyperglycemia medications other than metformin
Have a body mass index (BMI) between 25 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 (<1.5 years) ophthalmologic examination
Impaired renal estimated glomerular filtration rate (eGFR) <45 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 or current cardiovascular, respiratory, hepatic, renal, 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

Trial locations and contacts

2 sites in 1 country.

Germany2 sites

Profil Mainz GmbH & Co. KG
Mainz, Rhineland-Palatinate, 55116
Profil Institut für Stoffwechselforschung
Neuss, North Rhine-Westphalia, 41460

Other trials in Germany

About this study

Official title: The Effect of Tirzepatide on α and β Cell Function and Insulin Sensitivity in Patients With Type 2 Diabetes Mellitus

Conditions: Diabetes Mellitus, Type 2
Being tested: Tirzepatide, Semaglutide, Placebo
Medical subject headings: Diabetes Mellitus, Type 2

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
SemaglutideDrug
Administered SC
PlaceboDrug
Administered SC

Study groups in NCT03951753
Study group	Role	What they receive
Tirzepatide 15 mg	Experimental	Participants received 15 milligram (mg) tirzepatide administered subcutaneously (SC) once weekly for 28 weeks. Receives: Drug: Tirzepatide
Semaglutide 1 mg	Active comparator	Participants received 1 mg Semaglutide administered SC once weekly for 28 weeks. Receives: Drug: Semaglutide
Placebo	Placebo comparator	Participants received Placebo administered SC once weekly for 28 weeks. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Total Clamp Disposition Index (cDI)
cDI is defined as the product of the M-value derived from the hyperinsulinemic euglycemic clamp over the last 30 minutes and total insulin secretion (ISR AUC0-120min) derived from the insulin secretion rate based on C-peptide using the using the deconvolution technique divided by the total glucose AUC0-120min from the hyperglycemic clamp portion of the study. Least squares (LS) mean was determined by analysis of covariance (ANCOVA) model for endpoint measures: log(Actual Measurement/Baseline) = log(Baseline) + Treatment (Type III sum of squares).
Measured: Baseline, Week 28

Secondary outcomes (8)

Change From Baseline in Fasting Glucose
Fasting glucose is a test to determine sugar levels in blood sample after an overnight fast. Fasting glucose was measured prior to standardized mixed-meal tolerance tests (sMMTT). LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares).
Measured: Baseline, Week 28
Change From Baseline in Postmeal Glucose
Total AUC from time zero to 240 minutes after start of the meal [AUC0-240min]) during sMMTT was evaluated. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares) and ANOVA model for baseline measures: Variable = Treatment (Type III sum of squares).
Measured: Baseline, Week 28
Change From Baseline in Hemoglobin A1c (HbA1c)
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by mixed model repeated measures; (MMRM) model for post-baseline measures: Variable = Baseline + Treatment + Time + Treatment*Time (Type III sum of squares).
Measured: Baseline, Week 28
Change From Baseline in Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min)
Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min) will be determined from C-peptide concentrations using the deconvolution technique. LS mean was determined by ANCOVA model for endpoint measures: log(Actual Measurement/Baseline) = log(Baseline) + Treatment (Type III sum of squares).
Measured: Baseline and Week 28
Change From Baseline in Hyperinsulinemic Euglycemic Clamp M-value
Hyperinsulinemic euglycemic clamp M-value is calculated from glucose infusion rate (GIR) over the last 30 minutes, corresponding to steady-state (+150 to +180 minutes), corrected for urine loss and space. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares).
Measured: Baseline, Week 28
Change From Baseline in Glucagon Concentration at Fasting
Glucagon concentration was measured prior to sMMTT. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares).
Measured: Baseline and Week 28
Change From Baseline in Glucagon Concentration at Postmeal
Total AUC from time zero to 240 minutes after start of the meal [AUC0-240min]) during sMMTT. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Treatment (Type III sum of squares).
Measured: Baseline and Week 28
Change From Baseline in Food Intake During Ad Libitum Meal
Ad libitum meal served buffet-style. Food intake was recorded during a 45 minute period. The sum of the caloric breakdown (carbohydrates, protein, and fats) was calculated from the respective nutritional information of the food items. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Treatment + Time + Treatment*Time (Type III sum of squares).
Measured: Baseline, Week 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Jun 20198 Apr 2021

First posted15 May 2019
Study start28 Jun 2019
Primary completion8 Apr 2021
Study completion8 Apr 2021

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 (2)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: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 117 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03951753
Sponsor's protocol ID: 17091
Other IDs: I8F-MC-GPGT, 2018-003343-37, 2018
Status last verified: Jun 2022
First submitted: 14 May 2019
Last updated: 20 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Heise T, DeVries JH, Urva S, Li J, Pratt EJ, Thomas MK, Mather KJ, Karanikas CA, Dunn J, Haupt A, Milicevic Z, Coskun T. Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes. Diabetes Care. 2023 May 1;46(5):998-1004. doi: 10.2337/dc22-1710.
PubMed 36857477
Heise T, Mari A, DeVries JH, Urva S, Li J, Pratt EJ, Coskun T, Thomas MK, Mather KJ, Haupt A, Milicevic Z. Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):418-429. doi: 10.1016/S2213-8587(22)00085-7. Epub 2022 Apr 22.
PubMed 35468322

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 20 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effect of Tirzepatide on α and β Cell Function and Insulin Sensitivity in Patients With Type 2 Diabetes Mellitus
ClinicalTrials.gov ID: NCT03951753
Acronym / sponsor ID: 17091
Conditions: Diabetes Mellitus, Type 2
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 117 participants (actual)
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Study start: 28 Jun 2019 (actual)
Primary completion: 8 Apr 2021 (actual)
Study completion: 8 Apr 2021 (actual)
First posted: 15 May 2019 (actual)
Results: Posted 20 Mar 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Tirzepatide 15 mg	Experimental	Drug: TirzepatideParticipants received 15 milligram (mg) tirzepatide administered subcutaneously (SC) once weekly for 28 weeks.
Semaglutide 1 mg	Active comparator	Drug: SemaglutideParticipants received 1 mg Semaglutide administered SC once weekly for 28 weeks.
Placebo	Placebo comparator	Drug: PlaceboParticipants received Placebo administered SC once weekly for 28 weeks.

Who may qualify

Ages: 20 to 74 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Have T2DM for at least 6 months
Treated with diet and exercise and stable dose(s) of metformin, with or without 1 additional stable dose of oral antihyperglycemia medication other than metformin, 3 months prior to study entry
Have a hemoglobin A1c (HbA1c) value at screening of ≥7% and ≤ 9.5 % if on metformin only; or ≥6.5% and ≤9.0% if on metformin in combination with oral antihyperglycemia medications other than metformin
Have a body mass index (BMI) between 25 and 45 kilograms per square meter (kg/m² ) inclusive, at screening; are of stable weight (±5%) >3 months prior to screening

Key exclusion criteria (3 listed)

Have a history of proliferative retinopathy or maculopathy as determined by the investigator based on a recent (<1.5 years) ophthalmologic examination
Impaired renal estimated glomerular filtration rate (eGFR) <45 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 or current cardiovascular, respiratory, hepatic, renal, 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

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 15 mg
SemaglutideAdministered SC	Drug	Semaglutide 1 mg
PlaceboAdministered SC	Drug	Placebo

Primary outcome

Change From Baseline in Total Clamp Disposition Index (cDI)
Time frame: Baseline, Week 28
cDI is defined as the product of the M-value derived from the hyperinsulinemic euglycemic clamp over the last 30 minutes and total insulin secretion (ISR AUC0-120min) derived from the insulin secretion rate based on C-peptide using the using the deconvolution technique divided by the total glucose AUC0-120min from the hyperglycemic clamp portion of the study. Least squares (LS) mean was determined by analysis of covariance (ANCOVA) model for endpoint measures: log(Actual Measurement/Baseline) = log(Baseline) + Treatment (Type III sum of squares).

8 secondary outcomes

Change From Baseline in Fasting Glucose
Time frame: Baseline, Week 28
Change From Baseline in Postmeal Glucose
Time frame: Baseline, Week 28
Change From Baseline in Hemoglobin A1c (HbA1c)
Time frame: Baseline, Week 28
Change From Baseline in Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min)
Time frame: Baseline and Week 28
Change From Baseline in Hyperinsulinemic Euglycemic Clamp M-value
Time frame: Baseline, Week 28
Change From Baseline in Glucagon Concentration at Fasting
Time frame: Baseline and Week 28
Change From Baseline in Glucagon Concentration at Postmeal
Time frame: Baseline and Week 28
Change From Baseline in Food Intake During Ad Libitum Meal
Time frame: Baseline, Week 28

Results and safety

Results posted to the registry on 20 Mar 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tirzepatide 15 mg	45	41
Semaglutide 1 mg	44	43
Placebo	28	24

Primary outcome: Change From Baseline in Total Clamp Disposition Index (cDI)

Time frame: Baseline, Week 28. Least squares mean (Standard Error). Unit: pmol*m-2*L*min-2*kg-1

Measure	Tirzepatide 15 mg n = 39	Semaglutide 1 mg n = 39	Placebo n = 24
Value	1.9 (0.16)	1.1 (0.10)	0.0 (0.03)

Semaglutide 1 mg vs Placebo: Least Squares Mean Difference: 1.08 (95% CI 0.87 to 1.29), p <0.001, ANCOVA
Tirzepatide 15 mg vs Placebo: Least Squares Mean Difference: 1.92 (95% CI 1.59 to 2.24), p <0.001, ANCOVA
Tirzepatide 15 mg vs Semaglutide 1 mg: Least Squares Mean Difference: 0.84 (95% CI 0.46 to 1.21), p <0.001, ANCOVA

Population analysed: All randomly assigned participants who received at least 1 dose of study drug and have evaluable data.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Week 32. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	2 of 28 (7.1%)	18 of 28 (64.3%)	0 of 28
Semaglutide 1 mg	0 of 44 (0%)	43 of 44 (97.7%)	0 of 44
Tirzepatide 15 mg	1 of 45 (2.2%)	41 of 45 (91.1%)	0 of 45

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36857477Heise T, DeVries JH, Urva S, Li J, Pratt EJ, Thomas MK, Mather KJ, Karanikas CA, Dunn J, Haupt A, Milicevic Z, Coskun T. Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes. Diabetes Care. 2023 May 1;46(5):998-1004. doi: 10.2337/dc22-1710.
Derived from this study: PubMed 35468322Heise T, Mari A, DeVries JH, Urva S, Li J, Pratt EJ, Coskun T, Thomas MK, Mather KJ, Haupt A, Milicevic Z. Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):418-429. doi: 10.1016/S2213-8587(22)00085-7. Epub 2022 Apr 22.
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

2 sites 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 and Semaglutide in people with Diabetes Mellitus, Type 2, run by Eli Lilly and Company at 2 sites in Germany.

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 4 inclusion and 3 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 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Germany. 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 Mar 2023). 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 From Baseline in Total Clamp Disposition Index (cDI) (time frame: Baseline, Week 28). 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 NCT03951753, which also lists 2 linked publications.

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 Mar 2023.