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NCT03861039

A Long-term Safety Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes

Completed Phase 3 Results posted Last updated 14 February 2022
What this trial tests

Phase 3 trial testing Tirzepatide in Type 2 Diabetes Mellitus in 443 participants. Completed in 16 February 2021.

Timeline
30 March 2019
Primary endpoint
26 January 2021
16 February 2021

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment443
Start date30 March 2019
Primary completion26 January 2021
Estimated completion16 February 2021
Sites34 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

20 and older, any sex, with Type 2 Diabetes Mellitus. 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.

Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration Primary · Baseline through Week 52

An SAE is any AE from this study that results in one of the following outcomes: * Death * Initial or prolonged inpatient hospitalization * A life-threatening experience (that is, immediate risk of dying) * Persistent or significant disability/incapacity * Congenital anomaly/birth defect. * Important medical events that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the patient or may require. A summary of all SAE's, regardless of causality, is located in the Reported Adverse Events section.

GroupValue95% CI
5 mg Tirzepatide0
10 mg Tirzepatide1
15 mg Tirzepatide1
Change From Baseline in Hemoglobin A1c (HbA1c) Secondary · Baseline, Week 52

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model for post-baseline measures: Variable = Baseline + oral antihyperglycemic medication (OAM) Group 1 + Treatment + Time + Treatment\*Time (Type III sum of squares).

GroupValue95% CI
5 mg Tirzepatide-2.57± 0.075
10 mg Tirzepatide-2.98± 0.075
15 mg Tirzepatide-3.02± 0.077
Percentage of Participants Who Achieve HbA1c <7% Secondary · Week 52

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

GroupValue95% CI
5 mg Tirzepatide92.57
10 mg Tirzepatide97.95
15 mg Tirzepatide96.55
Change From Baseline in Fasting Serum Glucose Secondary · Baseline, Week 52

Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + OAM Group 1 + Treatment + Time + Treatment\*Time (Type III sum of squares).

GroupValue95% CI
5 mg Tirzepatide-58.6± 1.75
10 mg Tirzepatide-71.2± 1.75
15 mg Tirzepatide-74.4± 1.81
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values Secondary · Baseline, Week 52

The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. LS mean was determined by analysis of covariance (ANCOVA) model for endpoint measures: Variable = Baseline + OAM Group 1 + Treatment (Type III sum of squares).

GroupValue95% CI
5 mg Tirzepatide-80.0± 1.91
10 mg Tirzepatide-94.1± 1.92
15 mg Tirzepatide-96.3± 1.99
Change From Baseline in Body Weight Secondary · Baseline, Week 52

LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + OAM Group 1 + Treatment + Time + Treatment\*Time (Type III sum of squares).

GroupValue95% CI
5 mg Tirzepatide-3.8± 0.51
10 mg Tirzepatide-7.5± 0.51
15 mg Tirzepatide-10.2± 0.52
Percentage of Participants Who Achieve Weight Loss of ≥5% From Baseline Secondary · Week 52

Percentage of Participants who Achieve Weight Loss of ≥5% from Baseline

GroupValue95% CI
5 mg Tirzepatide43.92
10 mg Tirzepatide70.55
15 mg Tirzepatide84.14
Change From Baseline in Fasting Insulin Secondary · Baseline, Week 52

LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment\*Time (Type III sum of squares).

GroupValue95% CI
5 mg Tirzepatide6.2± 2.68
10 mg Tirzepatide-4.8± 2.21
15 mg Tirzepatide-7.7± 2.16
Change From Baseline in Fasting C-Peptide Secondary · Baseline, Week 52

LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treatment\*Time (Type III sum of squares).

GroupValue95% CI
5 mg Tirzepatide-0.12± 0.044
10 mg Tirzepatide-0.28± 0.040
15 mg Tirzepatide-0.34± 0.040
Change From Baseline in Homeostasis Model Assessment B (HOMA-2B) (Insulin) Secondary · Baseline, Week 52

The HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) and to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. The change from baseline for fasting insulin concentrations are presented as insulin secretion (HOMA2-%B) and insulin sensitivity (HOMA2-%S). LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treat

GroupValue95% CI
5 mg Tirzepatide39.7± 2.16
10 mg Tirzepatide44.9± 2.40
15 mg Tirzepatide49.2± 2.60
Change From Baseline in HOMA-2S (Insulin) Secondary · Baseline, Week 52

The HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) and to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. The change from baseline for fasting insulin concentrations are presented as insulin secretion (HOMA2-%B) and insulin sensitivity (HOMA2-%S). LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + OAM Group 1 + Treatment + Time + Treat

GroupValue95% CI
5 mg Tirzepatide-0.1± 3.37
10 mg Tirzepatide16.7± 4.23
15 mg Tirzepatide24.1± 4.66
Number of Participants With Hypoglycemia Incidence and Rate With Blood Glucose <54 mg/dL or Severe Hypoglycemia, Exclude Hypoglycemic Events Occurring After Initiation of a New Antihyperglycemic Therapy Secondary · Baseline through Week 56

The hypoglycemia events were defined by participant reported events with blood glucose \<54mg/dL (\<3.0 mmol/L) or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.

GroupValue95% CI
5 mg Tirzepatide1
10 mg Tirzepatide1
15 mg Tirzepatide3

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline through Week 56. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

5 mg Tirzepatide
Serious: 2/148 (1%)
Deaths: 0/148
10 mg Tirzepatide
Serious: 11/147 (7%)
Deaths: 0/147
15 mg Tirzepatide
Serious: 11/148 (7%)
Deaths: 0/148

Serious adverse events (25 terms)

ReactionSystem5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
CataractEye disorders
Angina pectorisCardiac disorders
Atrioventricular block completeCardiac disorders
Vertigo positionalEar and labyrinth disorders
Eyelid ptosisEye disorders
Macular fibrosisEye disorders
Colitis ulcerativeGastrointestinal disorders
CholelithiasisHepatobiliary disorders
AppendicitisInfections and infestations
Diabetic gangreneInfections and infestations
Pneumonia legionellaInfections and infestations
Clavicle fractureInjury, poisoning and procedural complications
Radius fractureInjury, poisoning and procedural complications
Joint contractureMusculoskeletal and connective tissue disorders
Spinal ligament ossificationMusculoskeletal and connective tissue disorders
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder papillomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Facial paralysisNervous system disorders
NephrolithiasisRenal and urinary disorders
UreterolithiasisRenal and urinary disorders
Coronary artery bypassSurgical and medical procedures
Intra-cerebral aneurysm operationSurgical and medical procedures
Other adverse events (266 terms — click to expand)

ReactionSystem5 mg Tirzepatide10 mg Tirzepatide15 mg Tirzepatide
NauseaGastrointestinal disorders
NasopharyngitisInfections and infestations
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
VomitingGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Abdominal discomfortGastrointestinal disorders
Lipase increasedInvestigations
Weight decreasedInvestigations
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
GastroenteritisInfections and infestations
Abdominal distensionGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
MalaiseGeneral disorders
Abdominal pain upperGastrointestinal disorders
InfluenzaInfections and infestations
Gastrointestinal disorderGastrointestinal disorders
Injection site reactionGeneral disorders
Herpes zosterInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Renal cystRenal and urinary disorders
Dry skinSkin and subcutaneous tissue disorders
EczemaSkin and subcutaneous tissue disorders
VertigoEar and labyrinth disorders
Diabetic retinopathyEye disorders
Dental cariesGastrointestinal disorders
Faeces softGastrointestinal disorders
FatigueGeneral disorders
CystitisInfections and infestations
PharyngitisInfections and infestations
RhinitisInfections and infestations
Foot fractureInjury, poisoning and procedural complications
WoundInjury, poisoning and procedural complications
Amylase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Dizziness posturalNervous system disorders
HypoaesthesiaNervous system disorders

Most-reported serious reactions: Cataract, Angina pectoris, Atrioventricular block complete, Vertigo positional, Eyelid ptosis, Macular fibrosis, Colitis ulcerative, Cholelithiasis.

Data from ClinicalTrials.gov NCT03861039 adverse events section.

Sponsor's own description

The purpose of this study is to determine the long-term safety of the study drug tirzepatide in combination with oral antihyperglycemic medications in participants with type 2 diabetes.

Publications & conference data

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

  1. The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials.
    Min T, Bain SC. · · 2021 · cited 176× · PMID 33325008 · DOI 10.1007/s13300-020-00981-0
  2. Safety and efficacy of tirzepatide as an add-on to single oral antihyperglycaemic medication in patients with type 2 diabetes in Japan (SURPASS J-combo): a multicentre, randomised, open-label, parallel-group, phase 3 trial.
    Kadowaki T, Chin R, Ozeki A, Imaoka T, et al · · 2022 · cited 84× · PMID 35914542 · DOI 10.1016/s2213-8587(22)00187-5
  3. Transforming obesity: The advancement of multi-receptor drugs.
    Kusminski CM, Perez-Tilve D, Müller TD, DiMarchi RD, et al · · 2024 · cited 77× · PMID 39059360 · DOI 10.1016/j.cell.2024.06.003
  4. 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
  5. Tirzepatide and prevention of chronic kidney disease.
    Bosch C, Carriazo S, Soler MJ, Ortiz A, et al · · 2023 · cited 46× · PMID 37151412 · DOI 10.1093/ckj/sfac274
  6. Clinical perspectives on the use of the GIP/GLP-1 receptor agonist tirzepatide for the treatment of type-2 diabetes and obesity.
    Gallwitz B. · · 2022 · cited 42× · PMID 36313764 · DOI 10.3389/fendo.2022.1004044
  7. Tirzepatide: A Promising Drug for Type 2 Diabetes and Beyond.
    Dutta P, Kumar Y, Babu AT, Giri Ravindran S, et al · · 2023 · cited 16× · PMID 37265914 · DOI 10.7759/cureus.38379
  8. Tirzepatide: A Novel, Once-weekly Dual GIP and GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes.
    Kaneko S. · · 2022 · cited 15× · PMID 35949358 · DOI 10.17925/ee.2022.18.1.10

Verify or expand the search:

Other trials of Tirzepatide

Trials testing the same drug.

Other recruiting trials for Type 2 Diabetes Mellitus

Currently open trials in the same condition.

Other Eli Lilly and Company trials

Trials by the same sponsor.

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Data sources for this page

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/NCT03861039.

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