Trial reportDiabetes, obesity & metabolism2022

A phase 1 multiple-ascending dose study of tirzepatide in Japanese participants with type 2 diabetes.

Kenichi Furihata, Hanaka Mimura, Shweta Urva, Tomonori Oura, Kenji Ohwaki, Takeshi Imaoka

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2022. The graph read 1 number from its abstract, feeding 1 cell of the map: it supports the treatment in 1. It is linked to trial NCT07734792 (Effect of Tirzepatide on Functional Outcomes in Patients With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy), which is not on this map. Cited by 36 papers, 6 of them syntheses that pooled it.

1number the graph read from it
1cell of the map it votes in
36citing papers in PubMed, 6 pooled it
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

← favours the treatmentfavours the comparator →
-1.900 · no effect
Body weight & compositionfavours the treatment · against placebo · t2dfeeds one cell of the map
ls mean decreases -1.60-1.90 to -1.20P < .0001
Tirzepatide also resulted in LS mean decreases from baseline versus placebo at 8 weeks in HbA1c up to 1.6% (95% CI 1.2%-1.9%; P < .0001 for all treatment groups) and body weight up to 6.6 kg (95% CI 5.3-7.9; P < .0001 for all treatment groups).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

GIP/GLP-1 & amylin agonists×body weight & composition

SupportsOpen on the map →What to test next →

29 readable studies in this cell: 28 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
1.00replicated · 19 families support, 0 contradict · against placebo
Without it
1.00This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2022
ls mean decreases -1.60-1.90 to -1.20
Δ -17.3-18.1 to -16.6
NCT041846222,539 enrolled · 2019
Δ -13.5-14.6 to -12.5
NCT037306622,002 enrolled · 2018
Δ -9.00-9.80 to -8.30
NCT039879191,879 enrolled · 2019
Δ -1.70-2.60 to -0.70
NCT038829701,444 enrolled · 2019
Δ -9.80-10.8 to -8.80
NCT045379231,428 enrolled · 2020
Δ -10.7-11.5 to -9.90
Δ -10.4-11.2 to -9.50
NCT04657003938 enrolled · 2021
Δ -10.1-11.5 to -8.80
NCT04093752917 enrolled · 2019
Δ -6.50-7.40 to -5.60
NCT04660643783 enrolled · 2021
Δ -21.4-22.9 to -20.0
NCT05822830751 enrolled · 2023
Δ -6.50-8.10 to -4.90
NCT04847557731 enrolled · 2021
Δ -11.6-12.8 to -10.4
4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07734792 phase2 / phase3not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Effect of Tirzepatide on Functional Outcomes in Patients With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy: A Multicenter, Randomized, Controlled, Blinded Outcome Assessment Trial

TypeinterventionalSponsoryifang zhuRan2026 to 2028Enrolled430ConditionsAcute Ischemic Stroke (AIS)ArmsTirzepatide, Standard Medical Care (SMC)
5 · Its place in the literature

Who cites it

36 citing papers in PubMed, 6 syntheses or guidelines pooled it, 58 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Trial
  8. Trial
  9. Trial
  10. Review
  11. Review
  12. Article
  13. Article
  14. Tirzepatide increased force of contraction in the isolated human atrium.Naunyn-Schmiedeberg's archives of pharmacology · 2025
    Article
  15. Review
  16. Severe Insulin Resistance Syndromes: Clinical Spectrum and Management.International journal of molecular sciences · 2025
    Review
  17. Article
  18. Article
  19. Review
  20. Incretin-based therapy: a new horizon in diabetes management.Journal of diabetes and metabolic disorders · 2024
    Review
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Kenichi FurihataP-One Clinic, Tokyo, Japan.
Hanaka MimuraEli Lilly Japan K. K., Kobe, Japan.
Shweta UrvaEli Lilly and Company, Indianapolis, Indiana, USA.ORCID 0000-0002-3681-479X
Tomonori OuraEli Lilly Japan K. K., Kobe, Japan.ORCID 0000-0003-0872-8576
Kenji OhwakiEli Lilly Japan K. K., Kobe, Japan.ORCID 0000-0002-2842-8231
Takeshi ImaokaEli Lilly Japan K. K., Kobe, Japan.
Eli Lilly (Japan) · JPEli Lilly (United States) · USOno Clinic · JP

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

aimTo investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of tirzepatide in Japanese participants with type 2 diabetes (T2D).

methodsThis phase 1, double-blind, placebo-controlled, parallel-dose, multiple-ascending dose study randomized participants to once-weekly subcutaneous tirzepatide or placebo. The tirzepatide treatment groups were: 5 mg (5 mg, weeks 1-8), 10 mg (2.5 mg, weeks 1-2; 5 mg, weeks 3-4; 10 mg, weeks 5-8), and 15 mg (5 mg, weeks 1-2; 10 mg, weeks 3-6; 15 mg, weeks 7-8). The primary outcome was tirzepatide safety and tolerability.

resultsForty-eight participants were randomized. The most frequently reported treatment-emergent adverse events (AEs) were decreased appetite and gastrointestinal AEs, which were generally dose-dependent and mild in severity. The plasma tirzepatide concentration half-life was approximately 5 days. After 8 weeks of treatment, fasting plasma glucose decreased from baseline with tirzepatide versus placebo; the least squares (LS) mean decrease compared with placebo (95% confidence interval [CI]) was 52.7 (35.9-69.6), 69.1 (52.3-85.9), and 68.9 (53.2-84.6) mg/dL in the 5-, 10-, and 15-mg treatment groups, respectively (P < .0001 for all treatment groups). Tirzepatide also resulted in LS mean decreases from baseline versus placebo at 8 weeks in HbA1c up to 1.6% (95% CI 1.2%-1.9%; P < .0001 for all treatment groups) and body weight up to 6.6 kg (95% CI 5.3-7.9; P < .0001 for all treatment groups).

conclusionsAll tirzepatide doses were well tolerated. The safety, tolerability, PK, and PD profiles of tirzepatide support further evaluation of once-weekly dosing in Japanese people with T2D.

Indexed as

Diabetes Mellitus, Type 2Double-Blind MethodGastric Inhibitory PolypeptideGlycated HemoglobinHumansHypoglycemic AgentsJapanTirzepatideGastric Inhibitory PolypeptideGlycated HemoglobinHypoglycemic AgentsTirzepatideantidiabetic drugGIPGLP-1phase I-II study

Identifiers

PMID34647404
PMCPMC9299227
OpenAlexW3206180121

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.