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NCT03951753

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

Completed Phase 1 Results posted Last updated 20 March 2023
What this trial tests

Phase 1 trial testing Tirzepatide in Diabetes Mellitus, Type 2 in 117 participants. Completed in 8 April 2021.

Timeline
28 June 2019
Primary endpoint
8 April 2021
8 April 2021

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposebasic science
Enrollment117
Start date28 June 2019
Primary completion8 April 2021
Estimated completion8 April 2021
Sites2 locations across Germany

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

Adults 20 to 74, any sex, with Diabetes Mellitus, Type 2. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Total Clamp Disposition Index (cDI) Primary · 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).

GroupValue95% CI
Tirzepatide 15 mg1.9± 0.16
Semaglutide 1 mg1.1± 0.10
Placebo0.0± 0.03
Change From Baseline in Fasting Glucose Secondary · Baseline, Week 28

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).

GroupValue95% CI
Tirzepatide 15 mg-51.4± 2.30
Semaglutide 1 mg-42.4± 2.22
Placebo-4.3± 2.98
Change From Baseline in Postmeal Glucose Secondary · Baseline, Week 28

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).

GroupValue95% CI
Tirzepatide 15 mg-17414.0± 726.02
Semaglutide 1 mg14236.9± 709.53
Placebo459.2± 947.50
Change From Baseline in Hemoglobin A1c (HbA1c) Secondary · Baseline, Week 28

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).

GroupValue95% CI
Tirzepatide 15 mg2.05± 0.079
Semaglutide 1 mg-1.64± 0.078
Placebo0.29± 0.101
Change From Baseline in Total Insulin Secretion Rate During the 120-Minute Hyperglycemic Clamp (ISR0-120min) Secondary · Baseline and Week 28

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).

GroupValue95% CI
Tirzepatide 15 mg388.6± 20.17
Semaglutide 1 mg286.6± 15.82
Placebo7.4± 7.15
Change From Baseline in Hyperinsulinemic Euglycemic Clamp M-value Secondary · Baseline, Week 28

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).

GroupValue95% CI
Tirzepatide 15 mg19.2± 1.93
Semaglutide 1 mg10.7± 1.99
Placebo-0.6± 2.53
Change From Baseline in Glucagon Concentration at Fasting Secondary · Baseline and Week 28

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).

GroupValue95% CI
Tirzepatide 15 mg-3.6± 0.55
Semaglutide 1 mg-2.8± 0.55
Placebo0.8± 0.75
Change From Baseline in Glucagon Concentration at Postmeal Secondary · Baseline and Week 28

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).

GroupValue95% CI
Tirzepatide 15 mg-843.6± 86.26
Semaglutide 1 mg-502.0± 87.33
Placebo-205.9± 116.31
Change From Baseline in Food Intake During Ad Libitum Meal Secondary · Baseline, Week 28

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).

GroupValue95% CI
Tirzepatide 15 mg-348.4± 34.59
Semaglutide 1 mg-284.1± 33.94
Placebo-38.6± 45.17

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Week 32. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 2/28 (7%)
Deaths: 0/28
Semaglutide 1 mg
Serious: 0/44 (0%)
Deaths: 0/44
Tirzepatide 15 mg
Serious: 1/45 (2%)
Deaths: 0/45

Serious adverse events (3 terms)

ReactionSystemPlaceboSemaglutide 1 mgTirzepatide 15 mg
Acute myocardial infarctionCardiac disorders
Subacute pancreatitisGastrointestinal disorders
UreterolithiasisRenal and urinary disorders
Other adverse events (22 terms — click to expand)

ReactionSystemPlaceboSemaglutide 1 mgTirzepatide 15 mg
Decreased appetiteMetabolism and nutrition disorders
Early satietyGeneral disorders
DyspepsiaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
Injection site haematomaGeneral disorders
FatigueGeneral disorders
ConstipationGastrointestinal disorders
EructationGastrointestinal disorders
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
Abdominal distensionGastrointestinal disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
VomitingGastrointestinal disorders
Lipase increasedInvestigations
VertigoEar and labyrinth disorders
AstheniaGeneral disorders
Injection site painGeneral disorders
Abnormal loss of weightMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders

Most-reported serious reactions: Acute myocardial infarction, Subacute pancreatitis, Ureterolithiasis.

Data from ClinicalTrials.gov NCT03951753 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist.
    Willard FS, Douros JD, Gabe MB, Showalter AD, et al · · 2020 · cited 344× · PMID 32730231 · DOI 10.1172/jci.insight.140532
  2. 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.
    Heise T, Mari A, DeVries JH, Urva S, et al · · 2022 · cited 189× · PMID 35468322 · DOI 10.1016/s2213-8587(22)00085-7
  3. Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes.
    Heise T, DeVries JH, Urva S, Li J, et al · · 2023 · cited 128× · PMID 36857477 · DOI 10.2337/dc22-1710
  4. Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review.
    Chavda VP, Ajabiya J, Teli D, Bojarska J, et al · · 2022 · cited 114× · PMID 35807558 · DOI 10.3390/molecules27134315
  5. Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials.
    Karagiannis T, Malandris K, Avgerinos I, Stamati A, et al · · 2024 · cited 64× · PMID 38613667 · DOI 10.1007/s00125-024-06144-1
  6. Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Phase II/III Trials.
    Bhagavathula AS, Vidyasagar K, Tesfaye W. · · 2021 · cited 41× · PMID 34681215 · DOI 10.3390/ph14100991
  7. Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial.
    Qin W, Yang J, Ni Y, Deng C, et al · · 2024 · cited 27× · PMID 38850440 · DOI 10.1007/s12020-024-03896-z
  8. Bridging the gap between GLP1-receptor agonists and cardiovascular outcomes: evidence for the role of tirzepatide.
    Taktaz F, Fontanella RA, Scisciola L, Pesapane A, et al · · 2024 · cited 26× · PMID 38987789 · DOI 10.1186/s12933-024-02319-7

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03951753.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing