PMID- 22739142
OWN - NLM
STAT- MEDLINE
DCOM- 20121018
LR  - 20221207
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Print)
IS  - 0009-9236 (Linking)
VI  - 92
IP  - 2
DP  - 2012 Aug
TI  - LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with 
      type 2 diabetes in a randomized, placebo-controlled trial.
PG  - 158-69
LID - 10.1038/clpt.2012.58 [doi]
AB  - Thirty-six patients with type 2 diabetes mellitus (T2DM) were randomized 1:1:1 to 
      receive a once-daily oral dose of placebo or 150 or 300 mg of the dual 
      SGLT1/SGLT2 inhibitor LX4211 for 28 days. Relative to placebo, LX4211 enhanced 
      urinary glucose excretion by inhibiting SGLT2-mediated renal glucose 
      reabsorption; markedly and significantly improved multiple measures of glycemic 
      control, including fasting plasma glucose, oral glucose tolerance, and HbA(1c); 
      and significantly lowered serum triglycerides. LX4211 also mediated trends for 
      lower weight, lower blood pressure, and higher glucagon-like peptide-1 levels. In 
      a follow-up single-dose study in 12 patients with T2DM, LX4211 (300 mg) 
      significantly increased glucagon-like peptide-1 and peptide YY levels relative to 
      pretreatment values, probably by delaying SGLT1-mediated intestinal glucose 
      absorption. In both studies, LX4211 was well tolerated without evidence of 
      increased gastrointestinal side effects. These data support further study of 
      LX4211-mediated dual SGLT1/SGLT2 inhibition as a novel mechanism of action in the 
      treatment of T2DM.
FAU - Zambrowicz, B
AU  - Zambrowicz B
AD  - Lexicon Pharmaceuticals, Inc., The Woodlands, Texas, USA.
FAU - Freiman, J
AU  - Freiman J
FAU - Brown, P M
AU  - Brown PM
FAU - Frazier, K S
AU  - Frazier KS
FAU - Turnage, A
AU  - Turnage A
FAU - Bronner, J
AU  - Bronner J
FAU - Ruff, D
AU  - Ruff D
FAU - Shadoan, M
AU  - Shadoan M
FAU - Banks, P
AU  - Banks P
FAU - Mseeh, F
AU  - Mseeh F
FAU - Rawlins, D B
AU  - Rawlins DB
FAU - Goodwin, N C
AU  - Goodwin NC
FAU - Mabon, R
AU  - Mabon R
FAU - Harrison, B A
AU  - Harrison BA
FAU - Wilson, A
AU  - Wilson A
FAU - Sands, A
AU  - Sands A
FAU - Powell, D R
AU  - Powell DR
LA  - eng
SI  - ClinicalTrials.gov/NCT00962065
SI  - ClinicalTrials.gov/NCT01188863
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120704
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Glycosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transporter 1)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0 (Triglycerides)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 106388-42-5 (Peptide YY)
RN  - 6B4ZBS263Y 
      ((2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Blood Glucose/*drug effects
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Glucagon-Like Peptide 1/blood
MH  - Glucose Tolerance Test
MH  - Glycated Hemoglobin/drug effects/metabolism
MH  - Glycosides/administration & dosage/*therapeutic use
MH  - Humans
MH  - Hypoglycemic Agents/adverse effects/*therapeutic use
MH  - Intestinal Absorption
MH  - Male
MH  - Middle Aged
MH  - Peptide YY/blood
MH  - Sodium-Glucose Transporter 1/*antagonists & inhibitors
MH  - *Sodium-Glucose Transporter 2 Inhibitors
MH  - Triglycerides/blood
PMC - PMC3400893
EDAT- 2012/06/29 06:00
MHDA- 2012/10/19 06:00
PMCR- 2012/08/01
CRDT- 2012/06/29 06:00
PHST- 2012/06/29 06:00 [entrez]
PHST- 2012/06/29 06:00 [pubmed]
PHST- 2012/10/19 06:00 [medline]
PHST- 2012/08/01 00:00 [pmc-release]
AID - clpt201258 [pii]
AID - 10.1038/clpt.2012.58 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2012 Aug;92(2):158-69. doi: 10.1038/clpt.2012.58. Epub 2012 
      Jul 4.