PMID- 34647404
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20221207
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Print)
IS  - 1462-8902 (Linking)
VI  - 24
IP  - 2
DP  - 2022 Feb
TI  - A phase 1 multiple-ascending dose study of tirzepatide in Japanese participants 
      with type 2 diabetes.
PG  - 239-246
LID - 10.1111/dom.14572 [doi]
AB  - AIM: To investigate the safety, tolerability, pharmacokinetics (PK), and 
      pharmacodynamics (PD) of tirzepatide in Japanese participants with type 2 
      diabetes (T2D). METHODS: This 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. RESULTS: 
      Forty-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). CONCLUSIONS: All 
      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.
CI  - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & 
      Sons Ltd.
FAU - Furihata, Kenichi
AU  - Furihata K
AD  - P-One Clinic, Tokyo, Japan.
FAU - Mimura, Hanaka
AU  - Mimura H
AD  - Eli Lilly Japan K. K., Kobe, Japan.
FAU - Urva, Shweta
AU  - Urva S
AUID- ORCID: 0000-0002-3681-479X
AD  - Eli Lilly and Company, Indianapolis, Indiana, USA.
FAU - Oura, Tomonori
AU  - Oura T
AUID- ORCID: 0000-0003-0872-8576
AD  - Eli Lilly Japan K. K., Kobe, Japan.
FAU - Ohwaki, Kenji
AU  - Ohwaki K
AUID- ORCID: 0000-0002-2842-8231
AD  - Eli Lilly Japan K. K., Kobe, Japan.
FAU - Imaoka, Takeshi
AU  - Imaoka T
AD  - Eli Lilly Japan K. K., Kobe, Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20211118
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - OYN3CCI6QE (tirzepatide)
SB  - IM
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Double-Blind Method
MH  - Gastric Inhibitory Polypeptide
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects
MH  - Japan
PMC - PMC9299227
OTO - NOTNLM
OT  - GIP
OT  - GLP-1
OT  - antidiabetic drug
OT  - phase I-II study
COIS- KF has received consulting fees from Kissei Pharmaceutical. HM, TO, KO, and TI 
      are full-time employees of Eli Lilly Japan K. K. and own stock in Eli Lilly and 
      Company. SU is a full-time employee of Eli Lilly and Company, Indianapolis, 
      Indiana, and owns stock in Eli Lilly and Company.
EDAT- 2021/10/15 06:00
MHDA- 2022/04/01 06:00
PMCR- 2022/07/20
CRDT- 2021/10/14 06:57
PHST- 2021/09/29 00:00 [revised]
PHST- 2021/07/07 00:00 [received]
PHST- 2021/10/08 00:00 [accepted]
PHST- 2021/10/15 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2021/10/14 06:57 [entrez]
PHST- 2022/07/20 00:00 [pmc-release]
AID - DOM14572 [pii]
AID - 10.1111/dom.14572 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2022 Feb;24(2):239-246. doi: 10.1111/dom.14572. Epub 2021 
      Nov 18.