PMID- 34363224
OWN - NLM
STAT- MEDLINE
DCOM- 20220413
LR  - 20230805
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 179
IP  - 4
DP  - 2022 Feb
TI  - Glucagon-like peptide-1 in diabetes care: Can glycaemic control be achieved 
      without nausea and vomiting?
PG  - 542-556
LID - 10.1111/bph.15647 [doi]
AB  - Introduced less than two decades ago, glucagon-like peptide-1 receptor agonists 
      rapidly reshaped the field of Type 2 diabetes mellitus (T2DM) care by providing 
      glycaemic control in tandem with weight loss. However, FDA-approved GLP-1 
      receptor agonists are often accompanied by nausea and emesis and, in some lean 
      T2DM patients, by undesired anorexia. Importantly, the hypophagic and emetic 
      effects of GLP-1 receptor agonists are caused by activation of central GLP-1 
      receptors. This review summarizes two different approaches to mitigate the 
      incidence and severity of nausea and emesis related to GLP-1 receptor agonists: 
      conjugation with vitamin B(12) , or related corrin ring-containing compounds 
      ('corrination'), and development of dual agonists of GLP-1 receptors with 
      glucose-dependent insulinotropic polypeptide (GIP). Such approaches could lead to 
      the generation of GLP-1 receptor agonists with improved therapeutic efficacy, 
      thus decreasing treatment attrition, increasing patient compliance and extending 
      treatment to a broader population of T2DM patients. The data reviewed show that 
      it is possible to pharmacologically separate the emetic effects of GLP-1 receptor 
      agonists from their glucoregulatory action. LINKED ARTICLES: This article is part 
      of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the 
      other articles in this section visit 
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.
CI  - (c) 2021 The British Pharmacological Society.
FAU - Borner, Tito
AU  - Borner T
AD  - Department of Biobehavioral Health Sciences, University of Pennsylvania, School 
      of Nursing, Philadelphia, Pennsylvania, USA.
AD  - Department of Psychiatry, University of Pennsylvania, Perelman School of 
      Medicine, Philadelphia, Pennsylvania, USA.
FAU - Tinsley, Ian C
AU  - Tinsley IC
AD  - Department of Chemistry, Syracuse University, Syracuse, New York, USA.
FAU - Doyle, Robert P
AU  - Doyle RP
AD  - Department of Chemistry, Syracuse University, Syracuse, New York, USA.
AD  - Department of Medicine, State University of New York Upstate Medical University, 
      Syracuse, New York, USA.
AD  - Department of Pharmacology, State University of New York Upstate Medical 
      University, Syracuse, New York, USA.
FAU - Hayes, Matthew R
AU  - Hayes MR
AD  - Department of Biobehavioral Health Sciences, University of Pennsylvania, School 
      of Nursing, Philadelphia, Pennsylvania, USA.
AD  - Department of Psychiatry, University of Pennsylvania, Perelman School of 
      Medicine, Philadelphia, Pennsylvania, USA.
FAU - De Jonghe, Bart C
AU  - De Jonghe BC
AD  - Department of Biobehavioral Health Sciences, University of Pennsylvania, School 
      of Nursing, Philadelphia, Pennsylvania, USA.
AD  - Department of Psychiatry, University of Pennsylvania, Perelman School of 
      Medicine, Philadelphia, Pennsylvania, USA.
LA  - eng
GR  - R01 DK115762/DK/NIDDK NIH HHS/United States
GR  - R56 DK115762/DK/NIDDK NIH HHS/United States
GR  - R15 DK097675/DK/NIDDK NIH HHS/United States
GR  - R01 DK128443/DK/NIDDK NIH HHS/United States
GR  - R01 DK112812/DK/NIDDK NIH HHS/United States
GR  - R01 DK021397/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210914
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Emetics)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - IM
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Emetics/therapeutic use
MH  - Gastric Inhibitory Polypeptide/pharmacology/therapeutic use
MH  - Glucagon-Like Peptide 1
MH  - *Glucagon-Like Peptide-1 Receptor/agonists
MH  - Glycemic Control
MH  - Humans
MH  - Nausea/drug therapy
MH  - Vomiting/drug therapy
PMC - PMC8810668
MID - NIHMS1766033
OTO - NOTNLM
OT  - GIPR/GLP-1R dual agonists
OT  - area postrema
OT  - cobinamide
OT  - corrination
OT  - diabetes mellitus
OT  - emesis
OT  - glucose-dependent insulinotropic polypeptide
OT  - hindbrain
OT  - side effects
OT  - tirzepatide
OT  - vitamin B12
COIS- T.B. and I.C.T. have no conflicts to declare. R.P.D. is an inventor of patents 
      related to the B12/Cbi-Ex4 technology. B.C.D.J. receives research funding from 
      Eli Lilly and Company and Pfizer Inc. and provided remunerated consultancy 
      services for Pfizer Inc. not supporting these studies. R.P.D. is a scientific 
      advisory board member and received funds from Xeragenx LLC (St. Louis, NY) and 
      Balchem, New Hampton, New York, that were not used in support of these studies. 
      M.R.H. receives research funding from Eli Lilly and Company and Boehringer 
      Ingelheim that was not used in support of these studies.
EDAT- 2021/08/08 06:00
MHDA- 2022/04/14 06:00
PMCR- 2022/02/07
CRDT- 2021/08/07 06:24
PHST- 2021/07/21 00:00 [revised]
PHST- 2021/03/04 00:00 [received]
PHST- 2021/07/24 00:00 [accepted]
PHST- 2021/08/08 06:00 [pubmed]
PHST- 2022/04/14 06:00 [medline]
PHST- 2021/08/07 06:24 [entrez]
PHST- 2022/02/07 00:00 [pmc-release]
AID - BPH15647 [pii]
AID - 10.1111/bph.15647 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2022 Feb;179(4):542-556. doi: 10.1111/bph.15647. Epub 2021 Sep 
      14.