PMID- 24964723
OWN - NLM
STAT- MEDLINE
DCOM- 20150928
LR  - 20221207
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 78
IP  - 6
DP  - 2014 Dec
TI  - Exposure-response modelling for empagliflozin, a sodium glucose cotransporter 2 
      (SGLT2) inhibitor, in patients with type 2 diabetes.
PG  - 1407-18
LID - 10.1111/bcp.12453 [doi]
AB  - AIMS: To provide model-based clinical development decision support including dose 
      selection guidance for empagliflozin, an orally administered sodium glucose 
      cotransporter 2 inhibitor, through developed exposure-response (E-R) models for 
      efficacy and tolerability in patients with type 2 diabetes mellitus (T2DM). 
      METHODS: Five randomized, placebo-controlled, multiple oral dose studies of 
      empagliflozin in patients with T2DM (n = 974; 1-100 mg once daily, duration </=12 
      weeks) were used to develop E-R models for efficacy (glycosylated haemoglobin 
      [HbA1c ], fasting plasma glucose [FPG] and urinary glucose excretion). Two 
      studies (n = 748, 12 weeks) were used to evaluate tolerability E-R. RESULTS: The 
      efficacy model predicted maximal decreases in FPG and HbA1c of 16% and 0.6%, 
      respectively, assuming a baseline FPG concentration of 8 mm (144 mg dl(-1) ) and 
      10-25 mg every day empagliflozin targeted 80-90% of these maximums. Increases in 
      exposure had no effect on incidence rates of hypoglycaemia (n = 4), urinary tract 
      infection (n = 17) or genital/vulvovaginal-related (n = 16) events, although low 
      prevalence rates may have precluded more accurate evaluation. CONCLUSIONS: E-R 
      analyses indicated that 10 and 25 mg once daily empagliflozin doses achieved near 
      maximal glucose lowering efficacy.
CI  - (c) 2014 The British Pharmacological Society.
FAU - Riggs, Matthew M
AU  - Riggs MM
AD  - Metrum Research Group LLC, Tariffville, CT.
FAU - Seman, Leo J
AU  - Seman LJ
FAU - Staab, Alexander
AU  - Staab A
FAU - MacGregor, Thomas R
AU  - MacGregor TR
FAU - Gillespie, William
AU  - Gillespie W
FAU - Gastonguay, Marc R
AU  - Gastonguay MR
FAU - Woerle, Hans J
AU  - Woerle HJ
FAU - Macha, Sreeraj
AU  - Macha S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Blood Glucose)
RN  - 0 (Glucosides)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0 (hemoglobin A1c protein, human)
RN  - HDC1R2M35U (empagliflozin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Benzhydryl Compounds/pharmacokinetics/pharmacology/*therapeutic use
MH  - Blood Glucose/analysis
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Glucosides/pharmacokinetics/pharmacology/*therapeutic use
MH  - Glycated Hemoglobin/analysis
MH  - Glycosuria/urine
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Models, Biological
MH  - Randomized Controlled Trials as Topic
MH  - *Sodium-Glucose Transporter 2 Inhibitors
PMC - PMC4256629
OTO - NOTNLM
OT  - BI 10773
OT  - SGLT2 inhibitor
OT  - empagliflozin
OT  - exposure-response analyses
OT  - type 2 diabetes
EDAT- 2014/06/27 06:00
MHDA- 2015/09/29 06:00
PMCR- 2015/12/01
CRDT- 2014/06/27 06:00
PHST- 2013/10/14 00:00 [received]
PHST- 2014/06/20 00:00 [accepted]
PHST- 2014/06/27 06:00 [entrez]
PHST- 2014/06/27 06:00 [pubmed]
PHST- 2015/09/29 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - 10.1111/bcp.12453 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2014 Dec;78(6):1407-18. doi: 10.1111/bcp.12453.