PMID- 21251178
OWN - NLM
STAT- MEDLINE
DCOM- 20120109
LR  - 20141120
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 13
IP  - 5
DP  - 2011 May
TI  - A 5-week study of the pharmacokinetics and pharmacodynamics of LY2189265, a 
      novel, long-acting glucagon-like peptide-1 analogue, in patients with type 2 
      diabetes.
PG  - 426-33
LID - 10.1111/j.1463-1326.2011.01364.x [doi]
AB  - AIM: To investigate the safety, tolerability, pharmacokinetics and 
      pharmacodynamics of LY2189265 (LY), a novel, long-acting glucagen-like peptide-1 
      analogue, administered once weekly to subjects with type 2 diabetes. METHODS: 
      This was a placebo-controlled, parallel-group, subject- and investigator-blind 
      study of LY in subjects (N = 43) with type 2 diabetes mellitus controlled with 
      diet and exercise alone or with a single oral antidiabetic medication. Subjects 
      taking metformin or thiazolidinediones continued on their therapy. Subjects 
      receiving sulfonylurea, acarbose, repaglinide or nateglinide were switched to 
      metformin prior to enrollment. Subjects received five once-weekly doses of 0.05, 
      0.3, 1, 3, 5 or 8 mg. Effects on glucose, insulin and C-peptide concentrations 
      were determined during fasting and following standard test meals. The 
      pharmacokinetics of LY and its effects on HBA1c, glucagon, body weight, gastric 
      emptying and safety parameters were assessed. RESULTS: Once-weekly administration 
      of LY significantly reduced (p < 0.01) fasting plasma glucose, 2-h post-test meal 
      postprandial glucose and area under the curve (AUC) of glucose after test meals 
      at doses >/=1 mg. These effects were seen after the first dose and were sustained 
      through the weekly dosing cycle. Most doses produced statistically significant 
      increases in insulin and C-peptide AUC when normalized for glucose AUC. 
      Statistically significant reductions in HBA1c were observed for all dose groups 
      except 0.3 mg. The most commonly reported adverse effects (AEs) were nausea (35 
      events), headache (20 events), vomiting (18 events) and diarrhoea (8 events). 
      CONCLUSIONS: LY showed improvement in fasting and postprandial glycaemic 
      parameters when administered once weekly in subjects with type 2 diabetes. The 
      pharmacokinetics and safety profiles also support further investigation of this 
      novel agent.
CI  - (c) 2011 Blackwell Publishing Ltd.
FAU - Barrington, P
AU  - Barrington P
AD  - Eli Lilly and Company, Erl Wood, Surrey, UK. barringtonph@lilly.com
FAU - Chien, J Y
AU  - Chien JY
FAU - Showalter, H D H
AU  - Showalter HD
FAU - Schneck, K
AU  - Schneck K
FAU - Cui, S
AU  - Cui S
FAU - Tibaldi, F
AU  - Tibaldi F
FAU - Ellis, B
AU  - Ellis B
FAU - Hardy, T A
AU  - Hardy TA
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20110119
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Thiazolidinediones)
RN  - 62340-29-8 (Glucagon-Like Peptides)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9100L32L2N (Metformin)
RN  - WTT295HSY5 (dulaglutide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Area Under Curve
MH  - Blood Glucose/drug effects/metabolism
MH  - Cohort Studies
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Fasting/blood
MH  - Female
MH  - Glucagon-Like Peptide 1/*analogs & derivatives
MH  - Glucagon-Like Peptides/analogs & derivatives
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
MH  - Immunoglobulin Fc Fragments/administration & dosage/adverse effects/*pharmacology
MH  - Male
MH  - Metformin/therapeutic use
MH  - Middle Aged
MH  - Postprandial Period
MH  - Recombinant Fusion Proteins/administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
MH  - Thiazolidinediones/therapeutic use
MH  - Treatment Outcome
EDAT- 2011/01/22 06:00
MHDA- 2012/01/10 06:00
CRDT- 2011/01/22 06:00
PHST- 2011/01/22 06:00 [entrez]
PHST- 2011/01/22 06:00 [pubmed]
PHST- 2012/01/10 06:00 [medline]
AID - 10.1111/j.1463-1326.2011.01364.x [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2011 May;13(5):426-33. doi: 
      10.1111/j.1463-1326.2011.01364.x. Epub 2011 Jan 19.