PMID- 30091172
OWN - NLM
STAT- MEDLINE
DCOM- 20190819
LR  - 20210109
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Print)
IS  - 1462-8902 (Linking)
VI  - 21
IP  - 1
DP  - 2019 Jan
TI  - Linagliptin as add-on to empagliflozin in a fixed-dose combination in Japanese 
      patients with type 2 diabetes: Glycaemic efficacy and safety profile in a 
      two-part, randomized, placebo-controlled trial.
PG  - 136-145
LID - 10.1111/dom.13496 [doi]
AB  - AIMS: This two-part, double-blind, double-dummy, randomized, placebo-controlled 
      trial (83 sites) evaluated the efficacy and safety of empagliflozin (Empa) 10 or 
      25 mg and linagliptin (Lina) 5 mg fixed-dose combinations (FDCs) in Japanese 
      patients with type 2 diabetes mellitus (T2DM) who were poorly controlled with 
      Empa. MATERIALS AND METHODS: Patients (previously drug-naive or using one oral 
      antidiabetic drug for >/= 12 weeks) entered an open-label stabilization period (16 
      weeks, Empa 10 mg [Part A] or Empa 25 mg [Part B]). Subsequently, they received 
      Empa 10 mg plus placebo (Plc) for Empa/Lina10/5 (Empa/Plc 10/5; Part A) or Empa 
      25 mg plus Plc for Empa/Lina 25/5 (Empa/Plc 25/5; Part B) for 2 weeks. Patients 
      with HbA1c 7.5-10.0% were randomized (1:1) to a 24-week regimen of once-daily 
      Empa/Lina 10/5 (n = 107) or Empa/Plc 10/5 (n = 108) in Part A, or to Empa/Lina 
      25/5 (n = 116) or Empa/Plc 25/5 (n = 116) in Part B, with a 28-week extension 
      period in Part B. RESULTS: Change from baseline in HbA1c at Week 24 was greater 
      (P < 0.0001) with Empa/Lina than with Empa/Plc (primary outcome, Empa/Lina 10/5: 
      -0.94 vs -0.12%; adjusted mean difference, -0.82%; Empa/Lina 25/5: -0.91 vs 
      -0.33%; adjusted mean difference, -0.59%). Over 24- and 52-week periods, higher 
      proportions of patients achieved HbA1c < 7.0% and greater decreases in fasting 
      plasma glucose were observed with Empa/Lina compared with Empa/Plc. Empa/Lina was 
      well tolerated, with no unexpected adverse events or diabetic ketoacidosis. One 
      case of confirmed hypoglycaemia with Empa/Plc 25/5 was reported. CONCLUSIONS: 
      These results support Empa/Lina FDC as a potential option for Japanese patients 
      with T2DM who require combination therapy. ClinicalTrials.gov NCT02489968.
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  - Kawasaki Medical School, Kurashiki, Japan.
FAU - Haneda, Masakazu
AU  - Haneda M
AD  - Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
FAU - Tanaka, Yuko
AU  - Tanaka Y
AUID- ORCID: 0000-0002-0804-5807
AD  - Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
FAU - Lee, Ganghyuck
AU  - Lee G
AD  - Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
FAU - Shiki, Kosuke
AU  - Shiki K
AD  - Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
FAU - Miyamoto, Yuki
AU  - Miyamoto Y
AD  - Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan.
FAU - Solimando, Fernando
AU  - Solimando F
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
FAU - Lee, Jisoo
AU  - Lee J
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
FAU - Lee, Christopher
AU  - Lee C
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
FAU - George, Jyothis
AU  - George J
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT02489968
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180906
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Blood Glucose)
RN  - 0 (Drug Combinations)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 3X29ZEJ4R2 (Linagliptin)
RN  - HDC1R2M35U (empagliflozin)
MH  - Adult
MH  - Aged
MH  - *Benzhydryl Compounds/administration & dosage/adverse effects/therapeutic use
MH  - Blood Glucose/analysis
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Drug Combinations
MH  - Female
MH  - *Glucosides/administration & dosage/adverse effects/therapeutic use
MH  - Humans
MH  - *Hypoglycemic Agents/administration & dosage/therapeutic use
MH  - Japan
MH  - *Linagliptin/administration & dosage/adverse effects/therapeutic use
MH  - Male
MH  - Middle Aged
PMC - PMC6585831
OTO - NOTNLM
OT  - empagliflozin
OT  - glycaemic control
OT  - linagliptin
OT  - phase III study
OT  - randomized trial
OT  - type 2 diabetes
COIS- Boehringer Ingelheim International GmbH and Nippon Boehringer Ingelheim Co. Ltd. 
      were involved in the study design, data collection, data analysis and preparation 
      of the manuscript. Y. T., G. L., K. S. and Y.M. are employees of Nippon 
      Boehringer Ingelheim Co. Ltd. F. S., J. L. and J. G. are employees of Boehringer 
      Ingelheim GmbH & Co. KG. C. L. is a former employee of Boehringer Ingelheim GmbH 
      & Co. KG. K. K. has received research funding and/or honoraria for lectures from 
      Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., 
      Kowa Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Nippon 
      Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma, Ono Pharmaceutical Co. Ltd., 
      Sumitomo Dainippon Pharma Co. Ltd., Sanwa Kagaku Kenkyusho Co. Ltd., Taisho 
      Toyama Pharmaceutical Co. Ltd. and Takeda Pharmaceutical Co. Ltd. M. H. has 
      received research funding and/or honoraria for lectures from Astellas Pharma 
      Inc., Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., Johnson & Johnson, Kissei 
      Pharmaceutical Co. Ltd., Kowa Pharmaceutical Co. Ltd., Kyowa Hakko Kirin Co. 
      Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Nippon Boehringer Ingelheim Co. 
      Ltd., Novartis Pharma, Novo Nordisk Pharma, Ono Pharmaceutical Co. Ltd., Otsuka 
      Pharmaceutical Co. Ltd., Sanofi, Shionogi & Co. Ltd., Taisho Pharmaceutical Co. 
      Ltd., Taisho Toyama Pharmaceutical Co. Ltd. and Takeda Pharmaceutical Company 
      Ltd.
EDAT- 2018/08/10 06:00
MHDA- 2019/08/20 06:00
PMCR- 2019/06/20
CRDT- 2018/08/10 06:00
PHST- 2018/05/07 00:00 [received]
PHST- 2018/07/27 00:00 [revised]
PHST- 2018/08/04 00:00 [accepted]
PHST- 2018/08/10 06:00 [pubmed]
PHST- 2019/08/20 06:00 [medline]
PHST- 2018/08/10 06:00 [entrez]
PHST- 2019/06/20 00:00 [pmc-release]
AID - DOM13496 [pii]
AID - 10.1111/dom.13496 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2019 Jan;21(1):136-145. doi: 10.1111/dom.13496. Epub 2018 
      Sep 6.