PMID- 32068914
OWN - NLM
STAT- MEDLINE
DCOM- 20210728
LR  - 20221207
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 86
IP  - 7
DP  - 2020 Jul
TI  - Effects of the dual sodium-glucose linked transporter inhibitor, licogliflozin vs 
      placebo or empagliflozin in patients with type 2 diabetes and heart failure.
PG  - 1346-1356
LID - 10.1111/bcp.14248 [doi]
AB  - AIMS: Explore the efficacy, safety and tolerability of the dual sodium-glucose 
      cotransporter (SGLT) 1 and 2 inhibitor, licogliflozin in patients with type-2 
      diabetes mellitus (T2DM) and heart failure. METHODS: This multicentre, 
      parallel-group phase IIA study randomized 125 patients with T2DM and heart 
      failure (New York Heart Association II-IV; plasma N-terminal pro b-type 
      natriuretic peptide [NT-proBNP] >300 pg/mL) to licogliflozin (2.5 mg, 10 mg, 50 
      mg) taken at bedtime, empagliflozin (25 mg) or placebo (44 patients completed the 
      study). The primary endpoint was change from baseline in NT-proBNP after 12 
      weeks. Secondary endpoints included change from baseline in glycated haemoglobin, 
      fasting plasma glucose, weight, blood pressure, fasting lipid profile, 
      high-sensitivity c-reactive protein, and safety and tolerability. RESULTS: 
      Licogliflozin 10 mg for 12 weeks significantly reduced NT-proBNP vs placebo 
      (Geometric mean ratio 0.56 [95% confidence interval: 0.33, 0.95], P = .033). A 
      trend was observed with 50 mg licogliflozin (0.64 [95% confidence interval: 0.40, 
      1.03], P = .064), with no difference between licogliflozin and empagliflozin. The 
      largest numerical decreases in glycated haemoglobin were with licogliflozin 50 mg 
      (-0.58 +/- 0.34%) and empagliflozin (-0.44 +/- 1.18%) vs placebo (-0.04 +/- 0.91%). The 
      reduction in body weight was similar with licogliflozin 50 mg (-2.15 +/- 2.40 kg) 
      and empagliflozin (-2.25 +/- 1.89 kg). A numerical reduction in systolic blood 
      pressure was seen with licogliflozin 50 mg (-9.54 +/- 16.88 mmHg) and empagliflozin 
      (-6.98 +/- 15.03 mmHg) vs placebo (-2.85 +/- 11.97 mmHg). Adverse events (AEs) were 
      mild, including hypotension (6.5%), hypoglycaemia (8.1%) and inadequate diabetes 
      control (1.6%). The incidence of diarrhoea (4.9%) was lower than previously 
      reported. CONCLUSION: The reduction in NT-proBNP with licogliflozin suggests a 
      potential benefit of SGLT1 and 2 inhibition in patients with T2DM and heart 
      failure.
CI  - (c) 2020 The Authors. British Journal of Clinical Pharmacology published by John 
      Wiley & Sons Ltd on behalf of British Pharmacological Society.
FAU - de Boer, Rudolf A
AU  - de Boer RA
AD  - University of Groningen, University Medical Centre Groningen, Groningen, The 
      Netherlands.
FAU - Nunez, Julio
AU  - Nunez J
AD  - Servicio de Cardiologia, Hospital Clinico Universitario Valencia, Valencia, 
      Spain.
AD  - INCLIVA, Universidad de Valencia, CIBER Cardiovascular, Spain.
FAU - Kozlovski, Plamen
AU  - Kozlovski P
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Wang, Yi
AU  - Wang Y
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Proot, Pieter
AU  - Proot P
AUID- ORCID: 0000-0002-0595-794X
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Keefe, Deborah
AU  - Keefe D
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
LA  - eng
GR  - Novartis Pharma/International
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200310
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Anhydrides)
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Blood Glucose)
RN  - 0 (Glucosides)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 506T60A25R (Sorbitol)
RN  - 57J06X6EI0 (licogliflozin)
RN  - 9NEZ333N27 (Sodium)
RN  - HDC1R2M35U (empagliflozin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Anhydrides
MH  - Benzhydryl Compounds/adverse effects
MH  - Blood Glucose
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Double-Blind Method
MH  - Glucose
MH  - Glucosides
MH  - Glycated Hemoglobin
MH  - *Heart Failure/drug therapy
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects
MH  - Sodium
MH  - Sorbitol/analogs & derivatives
MH  - Treatment Outcome
PMC - PMC7318993
OTO - NOTNLM
OT  - biomarkers, heart failure, pharmacotherapy, type 2 diabetes
COIS- The UMCG, which employs R.A.d.B. has received research grants and/or fees from 
      AstraZeneca, Abbott, Bristol-Myers Squibb, Novartis, Novo Nordisk, and Roche. 
      R.A.d.B. has received speaker fees and travel expenses from Abbott, AstraZeneca, 
      Novartis, and Roche. J.N. has received speaker fees and travel expenses from 
      Novartis, AstraZeneca, Vifor Pharma and Boehringer Ingelheim. P.K., Y.W., P.P., 
      and D.K. are employed by and own stock in Novartis. R.A.d.B., J.N., P.K. and D.K. 
      were responsible for the concept and design of this study, with R.A.d.B., J.N., 
      P.K. and P.P. responsible for the study conduct. Data collection was carried out 
      by R.A.d.B, J.N., P.K. and P.P., while statistical analysis was carried out by 
      Y.W. All authors contributed equally to the development and writing of this 
      manuscript.
EDAT- 2020/02/19 06:00
MHDA- 2021/07/29 06:00
PMCR- 2020/03/10
CRDT- 2020/02/19 06:00
PHST- 2019/09/25 00:00 [received]
PHST- 2019/12/23 00:00 [revised]
PHST- 2020/01/26 00:00 [accepted]
PHST- 2020/02/19 06:00 [pubmed]
PHST- 2021/07/29 06:00 [medline]
PHST- 2020/02/19 06:00 [entrez]
PHST- 2020/03/10 00:00 [pmc-release]
AID - BCP14248 [pii]
AID - 10.1111/bcp.14248 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2020 Jul;86(7):1346-1356. doi: 10.1111/bcp.14248. Epub 2020 
      Mar 10.