PMID- 34033212
OWN - NLM
STAT- MEDLINE
DCOM- 20210811
LR  - 20221207
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Print)
IS  - 1462-8902 (Linking)
VI  - 23
IP  - 9
DP  - 2021 Sep
TI  - Efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes 
      and inadequate glycaemic control on sitagliptin.
PG  - 2099-2108
LID - 10.1111/dom.14448 [doi]
AB  - AIMS: To assess the efficacy, safety and tolerability of ipragliflozin 50 mg once 
      daily added to sitagliptin 50 mg once daily monotherapy in Japanese patients with 
      type 2 diabetes (T2D). MATERIALS AND METHODS: The results of two clinical trials 
      are reported. In both trials, patients had glycated haemoglobin (HbA1c) levels of 
      7.0% to 10.0% on sitagliptin 50 mg once daily 2 weeks prior to addition of 
      ipragliflozin or placebo. In one trial (Trial 843), patients were randomized 1:1 
      to addition of blinded ipragliflozin 50 mg once daily (n = 73) or placebo 
      (n = 70) for 24 weeks; the primary endpoint was efficacy (change in HbA1c at Week 
      24). In the other trial (Trial 849), open-label ipragliflozin 50 mg once daily 
      was added for 52 weeks (n = 77); the primary objective was to assess 
      safety/tolerability. RESULTS: In Trial 843, baseline characteristics were similar 
      between groups (mean age 60.5 years, HbA1c 8.0%); after 24 weeks, adding 
      ipragliflozin provided significantly greater reduction in HbA1c compared to 
      placebo: least squares mean difference -0.77% (95% confidence interval -0.98, 
      -0.57; P <0.001). In Trial 843, the incidences of adverse events (AEs) overall 
      and prespecified AEs of clinical interest (symptomatic hypoglycaemia, urinary 
      tract infection, genital infection, hypovolaemia, and polyuria/pollakiuria) were 
      similar between groups. In Trial 849, specific AEs with incidence >/=5% were 
      nasopharyngitis, pollakiuria, back pain, thirst, constipation, influenza and 
      arthralgia; drug-related AEs reported in >/=2 patients were pollakiuria, thirst and 
      constipation. CONCLUSIONS: Ipragliflozin 50 mg once daily added on to sitagliptin 
      50 mg once daily monotherapy provided significant improvement in glycaemic 
      control and was generally well tolerated in Japanese patients with T2D. 
      ClinicalTrials.gov: NCT02577003, NCT02564211.
CI  - (c) 2021 Merck Sharp & Dohme Crop. Diabetes, Obesity and Metabolism published by 
      John Wiley & Sons Ltd.
FAU - Kaku, Kohei
AU  - Kaku K
AUID- ORCID: 0000-0003-1574-0565
AD  - Kawasaki Medical School, Okayama, Japan.
FAU - Kadowaki, Takashi
AU  - Kadowaki T
AD  - Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate 
      School of Medicine, The University of Tokyo, Tokyo, Japan.
AD  - Toranomon Hospital, Tokyo, Japan.
FAU - Seino, Yutaka
AU  - Seino Y
AD  - Kansai Electric Power Hospital, Osaka, Japan.
AD  - Kansai Electric Power Medical Research Institute, Osaka, Japan.
FAU - Okamoto, Taro
AU  - Okamoto T
AUID- ORCID: 0000-0001-5494-462X
AD  - Japan Development, MSD K.K, Tokyo, Japan.
FAU - Shirakawa, Masayoshi
AU  - Shirakawa M
AD  - Japan Development, MSD K.K, Tokyo, Japan.
FAU - Sato, Asako
AU  - Sato A
AD  - Japan Development, MSD K.K, Tokyo, Japan.
FAU - O'Neill, Edward A
AU  - O'Neill EA
AD  - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
FAU - Engel, Samuel S
AU  - Engel SS
AUID- ORCID: 0000-0002-4439-6356
AD  - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
FAU - Kaufman, Keith D
AU  - Kaufman KD
AD  - Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02564211
SI  - ClinicalTrials.gov/NCT02577003
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210615
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Glucosides)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Thiophenes)
RN  - 3N2N8OOR7X (ipragliflozin)
RN  - 9100L32L2N (Metformin)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
SB  - IM
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Glucosides
MH  - Glycated Hemoglobin/analysis
MH  - Glycemic Control
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects
MH  - Japan/epidemiology
MH  - *Metformin/therapeutic use
MH  - Middle Aged
MH  - Sitagliptin Phosphate/adverse effects
MH  - Thiophenes
MH  - Treatment Outcome
PMC - PMC8453748
OTO - NOTNLM
OT  - DPP-4 inhibitor
OT  - SGLT2 inhibitor
OT  - combination therapy
OT  - incretins
COIS- KK has received scholarship grants from Boehringer Ingelheim, Daiichi Sankyo, 
      Taisho and Mitsubishi Tanabe; and fees for consulting and/or lectures from 
      Astellas, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Fujifilm, Kowa, 
      Mitsubishi Tanabe, MSD, Novo Nordisk Pharma, Ono, Sanwa Kagaku, Sumitomo 
      Dainippon, Taisho Toyama and Takeda. TK has received contract research funds from 
      AstraZeneca, and Takeda; joint research funds from Daiichi Sankyo; grants from 
      Astellas, Daiichi Sankyo, Eli Lilly, Kissei, Mitsubishi Tanabe, MSD, Novo 
      Nordisk, Ono, Sanofi, Sumitomo Dainippon, Taisho and Takeda; fees for consulting 
      and/or lectures from Abbott, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, 
      Cosmic, Daiichi Sankyo, Eli Lilly, Fujifilm, Johnson & Johnson, Kissei, Kowa, 
      Kyowa Hakko Kirin, Medical Review, Medical View, Medscape Education, Medtronic 
      Sofamor Danek, Mitsubishi Tanabe, MSD, Musashino Foods, Nipro, Novartis, Novo 
      Nordisk, Ono, Sanofi, Sanwa Kagaku, Sumitomo Dainippon, Taisho, Takeda and 
      Terumo; and has been an endowed chair for Asahi Mutual Life Insurance, Boehringer 
      Ingelheim, Kowa, Mitsubishi Tanabe, MSD, Novo Nordisk, Ono and Takeda. YS has 
      received contracted/collaborative research funds from Bayer, Boehringer Ingelheim 
      and Terumo; scholarship grants from Arklay, Novo Nordisk, Ono, Sumitomo Dainippon 
      and Taisho Toyama; and consulting and/or lectures fees from Becton Dickinson, 
      Boehringer Ingelheim, Kao, MSD, Novo Nordisk, Taisho, Taisho Toyama and Takeda. 
      TO, AS, MS, EAON, SSE, and KDK are current employees of MSD K.K., Tokyo, Japan, 
      or Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New 
      Jersey USA, and may own stock/stock options in Merck & Co., Inc., Kenilworth, NJ, 
      USA. No other potential conflicts of interest relevant to this article are 
      reported.
EDAT- 2021/05/26 06:00
MHDA- 2021/08/12 06:00
PMCR- 2021/09/21
CRDT- 2021/05/25 14:13
PHST- 2021/05/12 00:00 [revised]
PHST- 2021/01/19 00:00 [received]
PHST- 2021/05/23 00:00 [accepted]
PHST- 2021/05/26 06:00 [pubmed]
PHST- 2021/08/12 06:00 [medline]
PHST- 2021/05/25 14:13 [entrez]
PHST- 2021/09/21 00:00 [pmc-release]
AID - DOM14448 [pii]
AID - 10.1111/dom.14448 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2021 Sep;23(9):2099-2108. doi: 10.1111/dom.14448. Epub 2021 
      Jun 15.