PMID- 23838841
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20131218
LR  - 20231110
IS  - 1869-6953 (Print)
IS  - 1869-6961 (Electronic)
IS  - 1869-6961 (Linking)
VI  - 4
IP  - 2
DP  - 2013 Dec
TI  - Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple rising 
      doses of empagliflozin in patients with type 2 diabetes mellitus.
PG  - 331-45
LID - 10.1007/s13300-013-0030-2 [doi]
AB  - INTRODUCTION: This study examined the safety, tolerability, pharmacokinetics, and 
      pharmacodynamics of empagliflozin, a potent and highly selective sodium glucose 
      cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus 
      (T2DM). METHODS: A total of 48 patients with T2DM were randomized to receive one 
      of four doses of empagliflozin (2.5, 10, 25, or 100 mg qd) or placebo over 
      8 days. In every dose group, nine patients received active drug and three 
      received placebo. The primary endpoint was safety and tolerability. 
      Pharmacokinetic and pharmacodynamic parameters were measured as secondary 
      endpoints. RESULTS: Empagliflozin was rapidly absorbed, reaching peak levels 
      1.5-3.0 h after dosing and showed a biphasic decline. The mean terminal 
      elimination half-life ranged from 10 to 19 h. Increases in exposure (area under 
      the plasma concentration-time curve [AUC] and maximum concentration of analyte in 
      plasma [C max]) were approximately proportional with dose. Empagliflozin 
      increased the rate and total amount of glucose excreted in urine compared to 
      placebo. After administration of a single dose of empagliflozin, cumulative 
      amounts of glucose excreted in urine over 24 h ranged from 46.3 to 89.8 g, 
      compared with 5.84 g with placebo. Similar results were seen after multiple 
      doses. Fasting plasma glucose levels decreased by 17.2-25.8% with empagliflozin 
      and by 12.7% with placebo. The frequency of adverse events was 33.3-66.7% with 
      empagliflozin and 41.7% with placebo. There were no changes in urine volume or 
      micturition frequency under the controlled study conditions. CONCLUSION: Overall, 
      pharmacokinetic assessments demonstrated a dose-proportional increase in drug 
      exposure and support once-daily dosing. Elevated urinary glucose excretion was 
      observed with all doses. Multiple once-daily oral doses of empagliflozin 
      (2.5-100 mg) reduced plasma glucose and were well tolerated in patients with 
      T2DM. EudraCT (2007-000654-32).
FAU - Heise, Tim
AU  - Heise T
AD  - Profil Institut fur Stoffwechselforschung GmbH, Hellersbergstrasse 9, 41460, 
      Neuss, Germany, tim.heise@profil.com.
FAU - Seman, Leo
AU  - Seman L
FAU - Macha, Sreeraj
AU  - Macha S
FAU - Jones, Peter
AU  - Jones P
FAU - Marquart, Alexandra
AU  - Marquart A
FAU - Pinnetti, Sabine
AU  - Pinnetti S
FAU - Woerle, Hans J
AU  - Woerle HJ
FAU - Dugi, Klaus
AU  - Dugi K
LA  - eng
PT  - Journal Article
DEP - 20130710
PL  - United States
TA  - Diabetes Ther
JT  - Diabetes therapy : research, treatment and education of diabetes and related 
      disorders
JID - 101539025
PMC - PMC3889329
EDAT- 2013/07/11 06:00
MHDA- 2013/07/11 06:01
PMCR- 2013/07/10
CRDT- 2013/07/11 06:00
PHST- 2013/05/07 00:00 [received]
PHST- 2013/07/11 06:00 [entrez]
PHST- 2013/07/11 06:00 [pubmed]
PHST- 2013/07/11 06:01 [medline]
PHST- 2013/07/10 00:00 [pmc-release]
AID - 30 [pii]
AID - 10.1007/s13300-013-0030-2 [doi]
PST - ppublish
SO  - Diabetes Ther. 2013 Dec;4(2):331-45. doi: 10.1007/s13300-013-0030-2. Epub 2013 
      Jul 10.