PMID- 25263215
OWN - NLM
STAT- MEDLINE
DCOM- 20150714
LR  - 20181217
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 17
IP  - 1
DP  - 2015 Jan
TI  - Albiglutide does not impair the counter-regulatory hormone response to 
      hypoglycaemia: a randomized, double-blind, placebo-controlled, stepped glucose 
      clamp study in subjects with type 2 diabetes mellitus.
PG  - 82-90
LID - 10.1111/dom.12398 [doi]
AB  - AIM: To determine if the glucagon-like peptide-1 (GLP-1) receptor agonist 
      albiglutide, once weekly, impairs counter-regulatory responses during 
      hypoglycaemia. METHODS: We conducted a randomized, double-blind, parallel, 
      placebo-controlled study in subjects with type 2 diabetes mellitus. A single dose 
      of albiglutide 50 mg (n = 22) or placebo (n = 22) was administered on day 1. 
      Glucose was clamped on day 4 (to coincide with the approximate albiglutide 
      maximum plasma concentration) at 9.0, 5.0, 4.0, 3.3 and 2.8 mmol/l (162, 90, 72, 
      59.4 and 50.4 mg/dl), with a post-clamp recovery period to 3.9 mmol/l (70 mg/dl). 
      Hormone measurements were made at each plateau and adverse events (AEs) were 
      recorded. RESULTS: The counter-regulatory hormones glucagon, epinephrine, 
      norepinephrine, growth hormone and cortisol were appropriately suppressed when 
      plasma glucose levels were >4.0 mmol/l (>72 mg/dl), but increased in the 
      albiglutide and placebo groups with glucose levels <3.3 mmol/l (<59.4 mg/dl) in 
      response to hypoglycaemia. The area under the curve geometric mean ratios 
      (albiglutide : placebo), calculated from the clamped plateau of 4.0 mmol/l 
      (72 mg/dl) to the glucose recovery point, were not significantly different for 
      any of the counter-regulatory hormones. When plasma glucose levels were 
      >5.0 mmol/l (>90 mg/dl), albiglutide increased pancreatic beta-cell secretion of 
      C-peptide in a glucose-dependent manner to a greater extent than did placebo, and 
      it was suppressed in each group when levels were <4.0 mmol/l (<72 mg/dl). No 
      significant difference between groups was observed in the recovery time to 
      glucose level >/=3.9 mmol/l (>/=70 mg/dl). There were no clinically relevant 
      differences in AEs or other safety variables. CONCLUSIONS: A single 50-mg dose of 
      albiglutide was well tolerated and did not impair the counter-regulatory response 
      to hypoglycaemia. These data provide mechanistic evidence supporting the low 
      intrinsic hypoglycaemic potential of albiglutide.
CI  - (c) 2014 John Wiley & Sons Ltd.
FAU - Hompesch, M
AU  - Hompesch M
AD  - Profil Institute for Clinical Research, Inc., Chula Vista, CA, USA.
FAU - Jones-Leone, A
AU  - Jones-Leone A
FAU - Carr, M C
AU  - Carr MC
FAU - Matthews, J
AU  - Matthews J
FAU - Zhi, H
AU  - Zhi H
FAU - Young, M
AU  - Young M
FAU - Morrow, L
AU  - Morrow L
FAU - Reinhardt, R R
AU  - Reinhardt RR
LA  - eng
SI  - ClinicalTrials.gov/NCT01475734
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20141026
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Recombinant Proteins)
RN  - 5E7U48495E (rGLP-1 protein)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9007-92-5 (Glucagon)
SB  - IM
MH  - Adult
MH  - Blood Glucose/analysis
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Double-Blind Method
MH  - Down-Regulation/drug effects
MH  - Female
MH  - Glucagon/blood/*metabolism
MH  - Glucagon-Like Peptide 1/administration & dosage/adverse 
      effects/*agonists/*analogs & derivatives/genetics/therapeutic use
MH  - Glucose Clamp Technique
MH  - Humans
MH  - Hyperglycemia/prevention & control
MH  - Hypoglycemia/chemically induced/*prevention & control
MH  - Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use
MH  - Insulin/blood/metabolism
MH  - Insulin Secretion
MH  - Male
MH  - Middle Aged
MH  - Pancreas/*drug effects/metabolism
MH  - Recombinant Proteins/administration & dosage/adverse effects/therapeutic use
MH  - Up-Regulation/*drug effects
OTO - NOTNLM
OT  - GLP-1 analogue
OT  - glucose metabolism
OT  - type 2 diabetes mellitus
EDAT- 2014/09/30 06:00
MHDA- 2015/07/15 06:00
CRDT- 2014/09/30 06:00
PHST- 2014/02/19 00:00 [received]
PHST- 2014/08/12 00:00 [revised]
PHST- 2014/09/21 00:00 [accepted]
PHST- 2014/09/30 06:00 [entrez]
PHST- 2014/09/30 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
AID - 10.1111/dom.12398 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2015 Jan;17(1):82-90. doi: 10.1111/dom.12398. Epub 2014 Oct 
      26.