PMID- 23631443
OWN - NLM
STAT- MEDLINE
DCOM- 20131203
LR  - 20211021
IS  - 2050-6511 (Electronic)
IS  - 2050-6511 (Linking)
VI  - 14
DP  - 2013 Apr 30
TI  - Safety, pharmacokinetics and pharmacodynamics of remogliflozin etabonate, a novel 
      SGLT2 inhibitor, and metformin when co-administered in subjects with type 2 
      diabetes mellitus.
PG  - 25
LID - 10.1186/2050-6511-14-25 [doi]
AB  - BACKGROUND: The sodium-dependent glucose co-transporter-2 (SGLT2) is expressed in 
      absorptive epithelia of the renal tubules. Remogliflozin etabonate (RE) is the 
      prodrug of remogliflozin, the active entity that inhibits SGLT2. An inhibitor of 
      this pathway would enhance urinary glucose excretion (UGE), and potentially 
      improve plasma glucose concentrations in diabetic patients. RE is intended for 
      use for the treatment of type 2 diabetes mellitus (T2DM) as monotherapy and in 
      combination with existing therapies. Metformin, a dimethylbiguanide, is an 
      effective oral antihyperglycemic agent widely used for the treatment of T2DM. 
      METHODS: This was a randomized, open-label, repeat-dose, two-sequence, cross-over 
      study in 13 subjects with T2DM. Subjects were randomized to one of two treatment 
      sequences in which they received either metformin alone, RE alone, or both over 
      three, 3-day treatment periods separated by two non-treatment intervals of 
      variable duration. On the evening before each treatment period, subjects were 
      admitted and confined to the clinical site for the duration of the 3-day 
      treatment period. Pharmacokinetic, pharmacodynamic (urine glucose and fasting 
      plasma glucose), and safety (adverse events, vital signs, ECG, clinical 
      laboratory parameters including lactic acid) assessments were performed at 
      check-in and throughout the treatment periods. Pharmacokinetic sampling occurred 
      on Day 3 of each treatment period. RESULTS: This study demonstrated the lack of 
      effect of RE on steady state metformin pharmacokinetics. Metformin did not affect 
      the AUC of RE, remogliflozin, or its active metabolite, GSK279782, although Cmax 
      values were slightly lower for remogliflozin and its metabolite after 
      co-administration with metformin compared with administration of RE alone. 
      Metformin did not alter the pharmacodynamic effects (UGE) of RE. Concomitant 
      administration of metformin and RE was well tolerated with minimal hypoglycemia, 
      no serious adverse events, and no increase in lactic acid. CONCLUSIONS: 
      Coadministration of metformin and RE was well tolerated in this study. The 
      results support continued development of RE as a treatment for T2DM. TRIAL 
      REGISTRATION: ClinicalTrials.gov, NCT00376038.
FAU - Hussey, Elizabeth K
AU  - Hussey EK
AD  - GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
FAU - Kapur, Anita
AU  - Kapur A
FAU - O'Connor-Semmes, Robin
AU  - O'Connor-Semmes R
FAU - Tao, Wenli
AU  - Tao W
FAU - Rafferty, Bryan
AU  - Rafferty B
FAU - Polli, Joseph W
AU  - Polli JW
FAU - James, Charles D Jr
AU  - James CD Jr
FAU - Dobbins, Robert L
AU  - Dobbins RL
LA  - eng
SI  - ClinicalTrials.gov/NCT00376038
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130430
PL  - England
TA  - BMC Pharmacol Toxicol
JT  - BMC pharmacology & toxicology
JID - 101590449
RN  - 0 (Blood Glucose)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Prodrugs)
RN  - 0 (Pyrazoles)
RN  - 0 (SLC5A2 protein, human)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 9100L32L2N (Metformin)
RN  - TR0QT6QSUL (remogliflozin etabonate)
SB  - IM
MH  - Adult
MH  - Blood Glucose/analysis
MH  - Cross-Over Studies
MH  - Diabetes Mellitus, Type 2/blood/drug therapy/urine
MH  - Female
MH  - Glucosides/*administration & dosage/blood/pharmacokinetics
MH  - Glycosuria
MH  - Humans
MH  - Hypoglycemic Agents/*administration & dosage/blood/pharmacokinetics
MH  - Male
MH  - Metformin/*administration & dosage/blood/pharmacokinetics
MH  - Middle Aged
MH  - Prodrugs/*administration & dosage/pharmacokinetics
MH  - Pyrazoles/*administration & dosage/blood/pharmacokinetics
MH  - Sodium-Glucose Transporter 2
MH  - Sodium-Glucose Transporter 2 Inhibitors
PMC - PMC3682882
EDAT- 2013/05/02 06:00
MHDA- 2013/12/16 06:00
PMCR- 2013/04/30
CRDT- 2013/05/02 06:00
PHST- 2012/02/17 00:00 [received]
PHST- 2013/04/18 00:00 [accepted]
PHST- 2013/05/02 06:00 [entrez]
PHST- 2013/05/02 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2013/04/30 00:00 [pmc-release]
AID - 2050-6511-14-25 [pii]
AID - 10.1186/2050-6511-14-25 [doi]
PST - epublish
SO  - BMC Pharmacol Toxicol. 2013 Apr 30;14:25. doi: 10.1186/2050-6511-14-25.