PMID- 29322610
OWN - NLM
STAT- MEDLINE
DCOM- 20190114
LR  - 20240314
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Print)
IS  - 1462-8902 (Linking)
VI  - 20
IP  - 5
DP  - 2018 May
TI  - Safety and efficacy of once-weekly semaglutide vs additional oral antidiabetic 
      drugs in Japanese people with inadequately controlled type 2 diabetes: A 
      randomized trial.
PG  - 1202-1212
LID - 10.1111/dom.13218 [doi]
AB  - AIM: To evaluate the safety and efficacy of once-weekly subcutaneous semaglutide 
      as monotherapy or combined with an oral antidiabetic drug (OAD) vs an additional 
      OAD added to background therapy in Japanese people with type 2 diabetes (T2D) 
      inadequately controlled on diet/exercise or OAD monotherapy. METHODS: In this 
      phase III, open-label trial, adults with T2D were randomized 2:2:1 to semaglutide 
      0.5 mg or 1.0 mg, or one additional OAD (a dipeptidyl peptidase-4 inhibitor, 
      biguanide, sulphonylurea, glinide, alpha-glucosidase inhibitor or thiazolidinedione) 
      with a different mode of action from that of background therapy. The primary 
      endpoint was number of adverse events (AEs) after 56 weeks. RESULTS: Baseline 
      characteristics were balanced between treatment arms (601 randomized). More AEs 
      were reported in the semaglutide 0.5 mg (86.2%) and 1.0 mg (88.0%) groups than in 
      the additional OAD group (71.7%). These were typically mild/moderate. 
      Gastrointestinal AEs were most frequent with semaglutide, which diminished over 
      time. The mean glycated haemoglobin (HbA1c) concentration (baseline 8.1%) was 
      significantly reduced with semaglutide 0.5 mg and 1.0 mg vs additional OAD (1.7% 
      and 2.0% vs 0.7%, respectively; estimated treatment difference [ETD] vs 
      additional OAD -1.08% and -1.37%, both P < .0001). Body weight (baseline 71.5 kg) 
      was reduced by 1.4 kg and 3.2 kg with semaglutide 0.5 mg and 1.0 mg, vs a 0.4-kg 
      increase with additional OAD (ETD -1.84 kg and -3.59 kg; both P < .0001). For 
      semaglutide-treated participants, >80% achieved an HbA1c concentration <7.0% 
      (Japanese Diabetes Society target). CONCLUSIONS: Semaglutide was well tolerated, 
      with no new safety issues identified. Semaglutide treatment significantly reduced 
      HbA1c and body weight vs additional OAD treatment in Japanese people with T2D.
CI  - (c) 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & 
      Sons Ltd.
FAU - Kaku, Kohei
AU  - Kaku K
AUID- ORCID: 0000-0003-1574-0565
AD  - Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, 
      Japan.
FAU - Yamada, Yuichiro
AU  - Yamada Y
AD  - Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University 
      Graduate School of Medicine, Akita, Japan.
FAU - Watada, Hirotaka
AU  - Watada H
AD  - Department of Metabolism and Endocrinology, Juntendo University Graduate School 
      of Medicine, Tokyo, Japan.
FAU - Abiko, Atsuko
AU  - Abiko A
AD  - Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan.
FAU - Nishida, Tomoyuki
AU  - Nishida T
AD  - Novo Nordisk Pharma Ltd., Tokyo, Japan.
FAU - Zacho, Jeppe
AU  - Zacho J
AD  - Novo Nordisk Pharma Ltd., Tokyo, Japan.
FAU - Kiyosue, Arihiro
AU  - Kiyosue A
AD  - Department of Internal Medicine, Tokyo-Eki Center-Building Clinic, Tokyo, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT02207374
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180221
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (GLP1R protein, human)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 53AXN4NNHX (semaglutide)
RN  - 62340-29-8 (Glucagon-Like Peptides)
SB  - IM
MH  - Administration, Oral
MH  - Aged
MH  - Combined Modality Therapy/adverse effects
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Drug Monitoring
MH  - Drug Resistance
MH  - Drug Therapy, Combination/adverse effects
MH  - Female
MH  - Follow-Up Studies
MH  - Glucagon-Like Peptide-1 Receptor/*agonists/metabolism
MH  - Glucagon-Like Peptides/*administration & dosage/adverse effects/therapeutic use
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - Hyperglycemia/*prevention & control
MH  - Hypoglycemia/chemically induced/*prevention & control
MH  - Hypoglycemic Agents/*administration & dosage/adverse effects/therapeutic use
MH  - Injections, Subcutaneous
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Weight Loss/drug effects
PMC - PMC5969242
OTO - NOTNLM
OT  - GLP-1 analogue
OT  - glycaemic control
OT  - incretin therapy
OT  - phase III study
OT  - randomized trial
OT  - type 2 diabetes
COIS- K.K. has received honoraria or consulting fees from Astellas Pharma, AstraZeneca 
      KK, MSD KK, Ono Pharmaceutical, Kissei Pharmaceutical, Kowa Pharmaceutical, 
      Sanofi KK, Sanwakagaku Kenkyusyo, Sumitomo Dainippon Pharma, Mitsubishi Tanabe 
      Pharma, Novartis Pharma KK, Novo Nordisk, Nippon Boehringer Ingelheim, Taisho 
      Toyama Pharmaceutical and Takeda, and research grants from Taisho Pharmaceutical, 
      Mitsubishi Tanabe Pharma and Nippon Boehringer Ingelheim. Y.Y. has received 
      honoraria or consulting fees from Novo Nordisk. H.W. has received honoraria for 
      consulting from Boehringer Ingelheim, Daiichi Sankyo, Dainippon Sumitomo Pharma, 
      Eli Lilly, Kowa Pharmaceutical, Merck Sharp & Dohme, Novo Nordisk, Novartis, Ono 
      Pharmaceutical, Sanofi, Sanwa Kagaku Kenkyusho, Takeda, Astellas Pharma, 
      Mitsubishi Tanabe Pharma, AstraZeneca, Kyowa Hakko Kirin and Kissei 
      Pharmaceutical, and grants from AstraZeneca, Boehringer Ingelheim, Daiichi 
      Sankyo, Dainippon Sumitomo Pharma, Eli Lilly, Kissei Pharma, Merck Sharp & Dohme, 
      Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Novartis, Novo Nordisk, Pfizer, 
      Sanofi, Sanwakagaku Kenkyusho, Takeda, Terumo Corp, Novartis, Astellas Pharma, 
      Abbott Japan, Ono Pharmaceutical, Kyowa Hakko Kirin Co. Ltd, Kowa Pharmaceutical, 
      Johnson & Johnson, Taisho Toyama Pharmaceutical, Nitto Boseki Company, Bayer, 
      Bristol-Myers Squibb and Benefit one Health care. A.A. has received consulting 
      and/or speaker fees from Novo Nordisk, Eli Lilly Japan, Nippon Boehringer 
      Ingelheim, Kowa Pharmaceutical, Novartis International, Astellas Pharma, 
      Mitsubishi Tanabe Pharma, Taisho Toyama Pharmaceutical, Kyowa Hakko Kirin, 
      Sumitomo Dainippon Pharma, Sanofi, MSD, Takeda, AstraZeneca, Ono Pharmaceutical, 
      Sanwa Kagaku Kenkyusho and Daiichi Sankyo, and research grants from Novo Nordisk. 
      T.N. is an employee of Novo Nordisk and holds shares in the company. J.Z. is an 
      employee of Novo Nordisk and holds shares in the company. A.K. has received 
      honoraria and consultation fees from AstraZeneca.
EDAT- 2018/01/13 06:00
MHDA- 2019/01/15 06:00
PMCR- 2018/05/25
CRDT- 2018/01/12 06:00
PHST- 2017/08/04 00:00 [received]
PHST- 2017/12/29 00:00 [revised]
PHST- 2018/01/08 00:00 [accepted]
PHST- 2018/01/13 06:00 [pubmed]
PHST- 2019/01/15 06:00 [medline]
PHST- 2018/01/12 06:00 [entrez]
PHST- 2018/05/25 00:00 [pmc-release]
AID - DOM13218 [pii]
AID - 10.1111/dom.13218 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2018 May;20(5):1202-1212. doi: 10.1111/dom.13218. Epub 2018 
      Feb 21.