PMID- 29545266
OWN - NLM
STAT- MEDLINE
DCOM- 20180625
LR  - 20181217
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
VI  - 67
IP  - 6
DP  - 2018 Jun
TI  - Native Oxyntomodulin Has Significant Glucoregulatory Effects Independent of 
      Weight Loss in Obese Humans With and Without Type 2 Diabetes.
PG  - 1105-1112
LID - 10.2337/db17-1331 [doi]
AB  - Oxyntomodulin (OXM), an enteroendocrine hormone, causes appetite suppression, 
      increased energy expenditure, and weight loss in obese humans via activation of 
      GLP-1 and glucagon receptors. However, the effects of OXM on glucose homeostasis 
      remain ill defined. To address this gap, we evaluated the effects of an i.v. 
      infusion of native OXM on insulin secretion rates (ISRs) and glycemic excursion 
      in a graded glucose infusion (GGI) procedure in two separate randomized, placebo 
      (PBO)-controlled, single-dose crossover trials in 12 overweight and obese 
      subjects without diabetes and in 12 obese subjects with type 2 diabetes mellitus 
      (T2DM), using the GLP-1 analog liraglutide (LIRA) as a comparator in T2DM. In 
      both groups, in the GGI, 3.0 pmol/kg/min of OXM significantly increased ISR and 
      blunted glycemic excursion relative to PBO. In T2DM, the effects of OXM were 
      comparable to those of LIRA, including restoration of beta-cell glucose 
      responsiveness to that of nonobese subjects without diabetes. Our findings 
      indicate that native OXM significantly augments glucose-dependent insulin 
      secretion acutely in obese subjects with and without diabetes, with effects 
      comparable to pharmacologic GLP-1 receptor activation and independent of weight 
      loss. Native OXM has potential to improve hyperglycemia via complementary and 
      independent induction of insulin secretion and weight loss.
CI  - (c) 2018 by the American Diabetes Association.
FAU - Shankar, Sudha S
AU  - Shankar SS
AUID- ORCID: 0000-0001-8432-8211
AD  - Merck & Co., Inc., Kenilworth, NJ sudhashankar@comcast.net.
FAU - Shankar, R Ravi
AU  - Shankar RR
AD  - Merck & Co., Inc., Kenilworth, NJ.
FAU - Mixson, Lori A
AU  - Mixson LA
AD  - Merck & Co., Inc., Kenilworth, NJ.
FAU - Miller, Deborah L
AU  - Miller DL
AD  - Merck & Co., Inc., Kenilworth, NJ.
FAU - Pramanik, Barnali
AU  - Pramanik B
AD  - Merck & Co., Inc., Kenilworth, NJ.
FAU - O'Dowd, Amy K
AU  - O'Dowd AK
AD  - Merck & Co., Inc., Kenilworth, NJ.
FAU - Williams, Donna M
AU  - Williams DM
AD  - Merck & Co., Inc., Kenilworth, NJ.
FAU - Frederick, Clay B
AU  - Frederick CB
AD  - Merck & Co., Inc., Kenilworth, NJ.
FAU - Beals, Chan R
AU  - Beals CR
AD  - Merck & Co., Inc., Kenilworth, NJ.
FAU - Stoch, S Aubrey
AU  - Stoch SA
AD  - Merck & Co., Inc., Kenilworth, NJ.
FAU - Steinberg, Helmut O
AU  - Steinberg HO
AD  - Merck & Co., Inc., Kenilworth, NJ.
FAU - Kelley, David E
AU  - Kelley DE
AD  - Merck & Co., Inc., Kenilworth, NJ.
LA  - eng
SI  - ClinicalTrials.gov/NCT01055340
SI  - ClinicalTrials.gov/NCT01373450
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180315
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Anti-Obesity Agents)
RN  - 0 (GLP1R protein, human)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Oxyntomodulin)
RN  - 0 (Receptors, Glucagon)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adult
MH  - Anti-Obesity Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Body Mass Index
MH  - Cohort Studies
MH  - Cross-Over Studies
MH  - Diabetes Mellitus, Type 2/blood/complications/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Glucagon-Like Peptide-1 Receptor/agonists/metabolism
MH  - Glucose/administration & dosage/adverse effects
MH  - Humans
MH  - Hyperglycemia/chemically induced/*prevention & control
MH  - Hypoglycemic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Infusions, Intravenous
MH  - Insulin/blood/metabolism
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/drug effects/metabolism
MH  - Male
MH  - Obesity/blood/complications/*drug therapy
MH  - Overweight/blood/complications/*drug therapy
MH  - Oxyntomodulin/administration & dosage/adverse effects/*therapeutic use
MH  - Receptors, Glucagon/agonists/metabolism
MH  - Young Adult
EDAT- 2018/03/17 06:00
MHDA- 2018/06/26 06:00
CRDT- 2018/03/17 06:00
PHST- 2017/11/02 00:00 [received]
PHST- 2018/03/06 00:00 [accepted]
PHST- 2018/03/17 06:00 [pubmed]
PHST- 2018/06/26 06:00 [medline]
PHST- 2018/03/17 06:00 [entrez]
AID - db17-1331 [pii]
AID - 10.2337/db17-1331 [doi]
PST - ppublish
SO  - Diabetes. 2018 Jun;67(6):1105-1112. doi: 10.2337/db17-1331. Epub 2018 Mar 15.