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Trial · Interventional

CompletedPhase 3Results postedRegistry data

A Study of Tirzepatide (LY3298176) Compared to Dulaglutide in Participants With Type 2 Diabetes

Short name SURPASS J-mono

NCTNCT03861052 (opens ClinicalTrials.gov in a new tab)Other id17077Other idI8F-JE-GPGO

Overview

Status
Completed
Phase
Phase 3
Enrollment
636 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Double masking
Countries
1 country

Japan

Start
7 May 2019
Primary completion
10 Mar 2021
Completion
31 Mar 2021
First posted
4 Mar 2019
Last update posted
14 Apr 2022
Conditions
Type 2 Diabetes

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2019202020212022
  1. Ph 3

    SURPASS J-mono

    NCT03861052

    7 May 2019 to 31 Mar 2021

Registry summary

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

The reason for this study is to see if the study drug tirzepatide (LY3298176) is effective and safe compared to dulaglutide in participants with type 2 diabetes in Japan.

Interventions

  • TirzepatideDrug
  • DulaglutideDrug

Arms4

  • Experimental

    5 mg Tirzepatide

    Participants received 5 milligram (mg) tirzepatide administered subcutaneously (SC) once weekly for 52 weeks.

  • Experimental

    10 mg Tirzepatide

    Participants received 10 mg tirzepatide administered SC once weekly for 52 weeks.

  • Experimental

    15 mg Tirzepatide

    Participants received 15 mg tirzepatide administered SC once weekly for 52 weeks.

  • Active comparator

    0.75 mg Dulaglutide

    Participants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change From Baseline in Hemoglobin A1c (HbA1c)

    Time frame · Baseline, Week 52

    Registry description

    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 + Baseline BMI Group (\<25 or \>=25 kg/m\^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment\*Time (Type III sum of squares).

Secondary outcomes(11)
  1. Percentage of Participants With HbA1c of <7.0%

    Time frame · Week 52

    Registry description

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

  2. Change From Baseline in Fasting Serum Glucose

    Time frame · Baseline, Week 52

    Registry description

    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 + Baseline BMI Group (\<25 or \>=25 kg/m\^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment\*Time (Type III sum of squares).

  3. Change From Baseline in Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

    Time frame · Baseline, Week 52

    Registry description

    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 with Baseline + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline BMI Group (\<25 or \>=25 kg/m\^2) + Washout of Antidiabetic Medication + Treatment (Type III sum of squares) as variables.

  4. Change From Baseline in Body Weight

    Time frame · Baseline, Week 52

    Registry description

    Change from baseline in body weight. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Washout of Antidiabetic Medication + Treatment + Time + Treatment\*Time (Type III sum of squares).

  5. Percentage of Participants Who Achieve Weight Loss ≥5% From Baseline

    Time frame · Week 52

    Registry description

    Percentage of participants who achieve weight loss ≥5% from baseline.

  6. Change From Baseline in Fasting Insulin

    Time frame · Baseline, Week 52

    Registry description

    Fasting Insulin is a test used to measure the amount of insulin in the body. LS mean was determined by MMRM model for post-baseline measures with log (Actual Measurement) = log (Baseline) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline BMI Group (\<25 or \>=25 kg/m\^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

  7. Change From Baseline in Fasting C-Peptide

    Time frame · Baseline, Week 52

    Registry description

    Fasting C-peptide is a test used to measure the amount of C-peptide in the body. A high level of C-peptide can mean that body is making too much insulin. LS mean was determined by MMRM model for post-baseline measures: log (Actual Measurement) = log (Baseline) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline BMI Group (\<25 or \>=25 kg/m\^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment\*Time (Type III sum of squares).

  8. Change From Baseline in Homeostasis Model Assessment B (HOMA-2B, Insulin)

    Time frame · Baseline, Week 52

    Registry description

    HOMA-2B is an estimated steady state beta cell function based on updated HOMA2 model. The HOMA2 model estimates steady state pancreatic beta cell function (%B) as a percentage of a normal reference population using simultaneously measured fasting plasma glucose and fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline BMI Group (\<25 or \>=25 kg/m\^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment\*Time (Type III sum of squares).

  9. Change From Baseline in HOMA-2S (Insluin)

    Time frame · Baseline, Week 52

    Registry description

    HOMA2-S is an estimated insulin sensitivity based on updated HOMA2 model. The HOMA2 model is a computer model that estimates insulin sensitivity (%S) as percentages of a normal reference population using simultaneously measured fasting plasma glucose and fasting insulin. LS mean was determined by MMRM model for post-baseline measures: log(Actual Measurement) = log(Baseline) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline BMI Group (\<25 or \>=25 kg/m\^2) + Washout of Antidiabetic Medication + Treatment + Time + Treatment\*Time (Type III sum of squares).

  10. Rate of Hypoglycemia With Glucose < 54 mg/dL or Severe Hypoglycemia

    Time frame · Baseline through Week 52

    Registry description

    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. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model for post-baseline comparisons between treatment and control group: number of episodes = baseline hypoglycemia incidence + baseline BMI Group (\<25 or \>=25 kg/m\^2) + washout of antidiabetic medication + baseline hemoglobin A1C (%) + treatment, with log (exposure in days/365.25) as an offset variable.

  11. Number of Participants With Anti-Tirzepatide Antibodies

    Time frame · Baseline through Week 52

    Registry description

    Number of participants with anti-tirzepatide antibodies. A participant is treatment emergent (TE) anti-drug antibody (ADA) evaluable if there is at least one non-missing test result for tirzepatide ADA for each of the baseline period and the postbaseline period. All percentages are relative to the total number of TE ADA evaluable participants in each treatment group. A TE ADA evaluable participant is considered to be TE ADA+ if the participant has at least one postbaseline titer that is a 4-fold or greater increase in titer from baseline measurement.

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· Baseline, Week 52

Change From Baseline in Hemoglobin A1c (HbA1c)

GroupValue (percentage of HbA1c)Spread
5 mg Tirzepatide-2.370.066
10 mg Tirzepatide-2.550.067
15 mg Tirzepatide-2.820.066
0.75 mg Dulaglutide-1.290.065
Secondary and other outcome results(7)
Secondary outcomeNumber· Week 52

Percentage of Participants With HbA1c of <7.0%

GroupValue (percentage of participants)
5 mg Tirzepatide93.67
10 mg Tirzepatide96.79
15 mg Tirzepatide99.37
0.75 mg Dulaglutide67.30
Secondary outcomeLeast squares mean· Baseline, Week 52

Change From Baseline in Fasting Serum Glucose

GroupValue (milligrams per decilitre (mg/dL))Spread
5 mg Tirzepatide-57.91.73
10 mg Tirzepatide-64.61.76
15 mg Tirzepatide-67.61.75
0.75 mg Dulaglutide-31.91.73
Secondary outcomeLeast squares mean· Baseline, Week 52

Change From Baseline in Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

GroupValue (mg/dL)Spread
5 mg Tirzepatide-59.51.46
10 mg Tirzepatide-64.21.50
15 mg Tirzepatide-68.61.50
0.75 mg Dulaglutide-42.21.48
Secondary outcomeLeast squares mean· Baseline, Week 52

Change From Baseline in Body Weight

GroupValue (kilogram (kg))Spread
5 mg Tirzepatide-5.80.41
10 mg Tirzepatide-8.50.42
15 mg Tirzepatide-10.70.41
0.75 mg Dulaglutide-0.50.41
Secondary outcomeNumber· Week 52

Percentage of Participants Who Achieve Weight Loss ≥5% From Baseline

GroupValue (percentage of participants)
5 mg Tirzepatide60.76
10 mg Tirzepatide82.05
15 mg Tirzepatide89.31
0.75 mg Dulaglutide10.69
Secondary outcomeLeast squares mean· Baseline, Week 52

Change From Baseline in Fasting Insulin

GroupValue (milliunits per litre (mU/L))Spread
5 mg Tirzepatide-1.070.374
10 mg Tirzepatide-1.870.344
15 mg Tirzepatide-2.000.335
0.75 mg Dulaglutide1.400.482
Secondary outcomeLeast squares mean· Baseline, Week 52

Change From Baseline in Fasting C-Peptide

GroupValue (micrograms per liter (ug/L))Spread
5 mg Tirzepatide-0.250.045
10 mg Tirzepatide-0.390.042
15 mg Tirzepatide-0.370.042
0.75 mg Dulaglutide0.010.052

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
5 mg TirzepatideParticipants received 5 mg tirzepatide administered SC once weekly for 52 weeks.0 / 1598 / 159131 / 159
10 mg TirzepatideParticipants received 10 mg tirzepatide administered SC once weekly for 52 weeks.0 / 15810 / 158121 / 158
15 mg TirzepatideParticipants received 15 mg tirzepatide administered SC once weekly for 52 weeks.0 / 1607 / 160134 / 160
0.75 mg DulaglutideParticipants received 0.75 mg dulaglutide administered SC once weekly for 52 weeks.0 / 15914 / 159120 / 159

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

Studies6

Studies that cite this trial.

Studies with results

4 studies on this page

PubMed tag: none · 2025

40 results

Insulin Sensitivity and Beta-Cell Function Following Tirzepatide in Japanese Patients with Type 2 Diabetes: A SURPASS J-mono Analysis.

Hamamoto et al. 2025Diabetes therapy : research, treatment and education of diabetes and related disorderscited by 3

PMID 39951042PMC11926299DOI 10.1007/s13300-025-01704-zPUB-39951042

Free to read · publisher termsCC BY-NC40 results

PubMed tag: none · 2024

9 results

Metabolic Abnormalities Following Tirzepatide Monotherapy in Japanese Patients with Type 2 Diabetes: A Phase 3 SURPASS J-mono Post Hoc Analysis.

Onishi et al. 2024Diabetes therapy : research, treatment and education of diabetes and related disorderscited by 4

PMID 38310163PMC10942919DOI 10.1007/s13300-024-01534-5PUB-38310163

Free to read · publisher termsCC BY-NC9 results

PubMed tag: none · 2023

22 results

Treatment Satisfaction and Quality of Life with Tirzepatide Versus Dulaglutide Among Japanese Patients with Type 2 Diabetes: Exploratory Evaluation of the SURPASS J-mono Trial.

Ishii et al. 2023Diabetes therapy : research, treatment and education of diabetes and related disorderscited by 8

PMID 37843771PMC10597937DOI 10.1007/s13300-023-01485-3PUB-37843771

Free to read · publisher termsCC BY-NC22 results

Indexing hint: Meta-analysis (pooled) · 2022

4 results

Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis.

Sattar et al. 2022Nature medicinecited by 268

PMID 35210595PMC8938269DOI 10.1038/s41591-022-01707-4PUB-35210595

CC BY4 results

More studies

2 studies on this page

PubMed tag: none · 2025

Association Between Early Weight Loss and Metabolic Outcomes with Tirzepatide in Japanese Patients with Type 2 Diabetes: A SURPASS J Post Hoc Analysis.

Mimura et al. 2025Diabetes therapy : research, treatment and education of diabetes and related disorders

PMID 40711720PMC12399453DOI 10.1007/s13300-025-01775-yPUB-40711720

Free to read · publisher termsCC BY-NC
Read at source

Indexing hint: Randomized controlled trial · 2022

Corrected

Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial.

Inagaki et al. 2022The lancet. Diabetes & endocrinologycited by 185

PMID 35914543DOI 10.1016/s2213-8587(22)00188-7PUB-35914543

Full text at the publisher

Eligibility

Who could join, as posted.

Sex
All
Age
from 20 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: Participant must: * Have been diagnosed with type 2 diabetes mellitus based on the World Health Organization classification before the screening visit. * Have HbA1c meeting the following criteria, as determined by the central laboratory at screening and baseline: * for participants who are oral antihyperglycemic medication (OAM)-naïve at screening, ≥7.0% to ≤10.0% at both screening and baseline. * for participants who have been taking OAM monotherapy at screening, ≥6.5% to ≤9.0% at screening, and ≥7.0% to ≤10.0% at baseline. * Have body mass index (BMI) of ≥23 kilograms per meter squared at screening. * Be of stable weight (±5%) during 3 months preceding screening; and agree to not initiate an intensive diet and/or exercise program during the study with the intent of reducing body weight other than the lifestyle and dietary measures for diabetes treatment. Exclusion Criteria: Participant must not: * Have type 1 diabetes mellitus. * Have had chronic or acute pancreatitis any time prior to study entry. * Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring immediate or urgent treatment. * Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss. * Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) enzyme level \>3.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. Participants with nonalcoholic fatty liver disease (NAFLD) are eligible for participation in this trial only if there ALT level is ≤3.0 the ULN for the reference range. * Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months. * Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2. * Have been taking weight loss drugs, including over-the-counter medications during the last 3 months.

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