The incretin/glucagon system as a target for pharmacotherapy of obesity.
GLP-1
dual agonist
glucagon
overweight
Journal
Obesity reviews : an official journal of the International Association for the Study of Obesity
ISSN: 1467-789X
Titre abrégé: Obes Rev
Pays: England
ID NLM: 100897395
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
08
09
2021
received:
04
06
2021
accepted:
08
09
2021
pubmed:
30
10
2021
medline:
22
3
2022
entrez:
29
10
2021
Statut:
ppublish
Résumé
Obesity is a chronic, multifactorial, relapsing disease. Despite multicomponent lifestyle interventions, including pharmacotherapy, maintaining bodyweight loss is challenging for many people. The pathophysiology of obesity is complex, and currently approved pharmacotherapies only target a few of the many pathways involved; thus, single-targeting agents have limited efficacy. Proglucagon-derived peptides, glucagon, and the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), represent attractive targets for managing obesity and metabolic disorders because they may have direct roles in multiple mechanisms including satiety, energy homeostasis, and lipolytic activity. Unimolecular dual and triple agonists targeting glucagon and incretin hormone receptors have been shown to promote bodyweight loss, lower glucose levels, and reduce food intake in animal models of obesity. Multiple dual receptor agonists are in clinical development for the treatment of obesity, including GLP-1/GIP and GLP-1/glucagon receptor agonists. The extent to which glucagon contributes to treatment effects remains to be understood, but it may promote bodyweight loss by reducing food intake, while concomitant GLP-1 receptor agonism ensures normal glucose control. Further research is required to fully understand the molecular mechanisms of action and metabolic effects of both dual and triple receptor agonists.
Identifiants
pubmed: 34713962
doi: 10.1111/obr.13372
pmc: PMC9286339
doi:
Substances chimiques
Glucagon-Like Peptide-1 Receptor
0
Incretins
0
Gastric Inhibitory Polypeptide
59392-49-3
Glucagon
9007-92-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13372Informations de copyright
© 2021 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.
Références
Brain Struct Funct. 2015 Mar;220(2):1213-9
pubmed: 24510283
J Clin Invest. 2021 Jun 15;131(12):
pubmed: 34003802
Am J Physiol. 1987 Jan;252(1 Pt 2):R160-5
pubmed: 3028165
Adv Exp Med Biol. 2018;1090:145-163
pubmed: 30390289
Diabetes Care. 2020 Mar;43(3):588-596
pubmed: 31949084
Physiol Rep. 2018 Sep;6(17):e13852
pubmed: 30187652
Diabetes Obes Metab. 2020 Aug;22(8):1328-1338
pubmed: 32196896
N Engl J Med. 2021 Aug 5;385(6):503-515
pubmed: 34170647
Diabetes Obes Metab. 2005 Nov;7(6):699-708
pubmed: 16219013
Am J Clin Nutr. 2001 Nov;74(5):579-84
pubmed: 11684524
J Clin Endocrinol Metab. 2020 Mar 1;105(3):
pubmed: 32077470
Endocr Rev. 2019 Oct 1;40(5):1353-1366
pubmed: 30920583
J Hepatol. 2019 Mar;70(3):531-544
pubmed: 30414863
Int J Obes (Lond). 2013 Oct;37(10):1391-8
pubmed: 23337772
Obes Rev. 2022 Feb;23(2):e13372
pubmed: 34713962
Am J Physiol Endocrinol Metab. 2016 Aug 1;311(2):E302-9
pubmed: 27245336
Nat Med. 2015 Jan;21(1):27-36
pubmed: 25485909
Mol Cell Endocrinol. 2020 Mar 1;503:110696
pubmed: 31891768
J Clin Invest. 1984 Mar;73(3):785-93
pubmed: 6142902
Cell Metab. 2019 Nov 5;30(5):987-996.e6
pubmed: 31447324
JAAPA. 2020 Aug;33(S8 Suppl 1):3-18
pubmed: 32756220
Comp Biochem Physiol B. 1971 May 15;39(1):69-82
pubmed: 5570026
Diabetes Care. 2021 Jun;44(6):1433-1442
pubmed: 34016612
Physiol Rev. 2015 Apr;95(2):513-48
pubmed: 25834231
Cureus. 2020 May 3;12(5):e7941
pubmed: 32499981
Physiol Res. 2011;60(6):941-50
pubmed: 21995902
N Engl J Med. 2008 Jul 17;359(3):229-41
pubmed: 18635428
Peptides. 2020 Mar;125:170225
pubmed: 31786282
Endocrinology. 2014 Sep;155(9):3484-92
pubmed: 24949663
Diabetes Obes Metab. 2012 Jun;14(6):500-10
pubmed: 22171657
Endocr Rev. 2018 Oct 1;39(5):719-738
pubmed: 29905825
Obes Res. 1999 Jan;7(1):1-8
pubmed: 10023724
J Diabetes Investig. 2018 Jan 3;:
pubmed: 29314731
Drugs. 2018 Jul;78(11):1113-1132
pubmed: 30014268
Anim Sci J. 2009 Dec;80(6):686-90
pubmed: 20163659
Sci Transl Med. 2018 Dec 19;10(472):
pubmed: 30567927
Diabetes Obes Metab. 2016 Jan;18(1):72-81
pubmed: 26434748
BMC Public Health. 2009 Mar 25;9:88
pubmed: 19320986
Lancet. 2018 Jun 30;391(10140):2607-2618
pubmed: 29945727
Gastroenterology. 2019 May;156(6):1627-1641.e1
pubmed: 30742833
J Clin Endocrinol Metab. 2003 Aug;88(8):3989-92
pubmed: 12915697
N Engl J Med. 2016 Nov 10;375(19):1834-1844
pubmed: 27633186
CNS Spectr. 2017 Dec;22(S1):29-38
pubmed: 29350126
Biophys J. 2015 Sep 15;109(6):1202-13
pubmed: 26340816
J Lipid Res. 1974 Jan;15(1):26-32
pubmed: 4359539
Am J Physiol. 1991 Jul;261(1 Pt 2):R162-5
pubmed: 1858943
Mol Metab. 2019 Feb;20:51-62
pubmed: 30578168
Arch Intern Med. 2000 Jul 24;160(14):2185-91
pubmed: 10904462
Diabetes. 2014 Nov;63(11):3711-20
pubmed: 24939425
Nat Rev Endocrinol. 2019 Feb;15(2):90-104
pubmed: 30446744
J Clin Invest. 1998 Feb 1;101(3):515-20
pubmed: 9449682
J Endocrinol. 2019 Nov;243(2):149-160
pubmed: 31454790
Nat Rev Dis Primers. 2017 Jun 15;3:17034
pubmed: 28617414
Sci Transl Med. 2013 Oct 30;5(209):209ra151
pubmed: 24174327
J Biol Chem. 1986 Sep 5;261(25):11880-9
pubmed: 3528148
Diabetes. 2019 May;68(5):906-917
pubmed: 30626611
Ann N Y Acad Sci. 2018 Jan;1411(1):53-64
pubmed: 28868615
Diabetologia. 2019 Nov;62(11):2066-2078
pubmed: 31338545
Diabetes Obes Metab. 2017 Jan;19(1):24-32
pubmed: 27501510
Pharmacol Biochem Behav. 1996 Jan;53(1):221-6
pubmed: 8848454
Biopolymers. 2012;98(5):443-50
pubmed: 23203689
Ann Transl Med. 2019 Mar;7(5):83
pubmed: 31019933
Expert Rev Clin Pharmacol. 2020 Jan;13(1):53-64
pubmed: 31770497
Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R992-8
pubmed: 12920059
Eur J Endocrinol. 2014 Oct;171(4):407-19
pubmed: 24986531
Nat Med. 2013 Jun;19(6):766-72
pubmed: 23685839
Diabetes Obes Metab. 2018 Aug;20(8):1836-1851
pubmed: 29938884
Endocr Pract. 2016 Jul;22 Suppl 3:1-203
pubmed: 27219496
Nature. 1996 Jan 4;379(6560):69-72
pubmed: 8538742
Front Psychol. 2021 Jan 14;11:530425
pubmed: 33519568
J Clin Invest. 1987 Feb;79(2):616-9
pubmed: 3543057
Lancet. 2018 Nov 17;392(10160):2180-2193
pubmed: 30293770
Int J Mol Sci. 2019 Aug 22;20(17):
pubmed: 31443356
Diabetes Obes Metab. 2018 Jan;20(1):60-68
pubmed: 28598027
BMC Med. 2016 Nov 29;14(1):191
pubmed: 27894343
N Engl J Med. 1961 May 4;264:893-7
pubmed: 13734109
Biochem Biophys Res Commun. 2017 Aug 19;490(2):247-252
pubmed: 28610922
P T. 2016 Mar;41(3):164-72
pubmed: 26957883
Obes Facts. 2015;8(6):402-24
pubmed: 26641646
J Clin Endocrinol Metab. 2020 Aug 1;105(8):
pubmed: 32459834
J Clin Invest. 2014 Oct;124(10):4473-88
pubmed: 25202980
Surg Obes Relat Dis. 2018 May;14(5):708-714
pubmed: 29776493
Neuron. 2006 Sep 21;51(6):811-22
pubmed: 16982425
Nature. 2002 Aug 8;418(6898):650-4
pubmed: 12167864
Can Fam Physician. 2020 Feb;66(2):117-125
pubmed: 32060194
J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2985-3023
pubmed: 24239920
Diabetologia. 2005 Sep;48(9):1700-13
pubmed: 16132964
Diabetes. 2013 Apr;62(4):1131-8
pubmed: 23248172
J Clin Endocrinol Metab. 1973 Nov;37(5):826-8
pubmed: 4749457
Expert Opin Pharmacother. 2020 Dec;21(17):2101-2114
pubmed: 32990096
Mol Metab. 2020 Dec;42:101080
pubmed: 32937194
Am J Physiol. 1992 Jun;262(6 Pt 2):R975-80
pubmed: 1621876
Diabetes. 2009 Oct;58(10):2258-66
pubmed: 19602537
Lancet. 2019 Jul 13;394(10193):121-130
pubmed: 31189511
Obes Surg. 2017 Jan;27(1):2-21
pubmed: 27957699
Int J Obes (Lond). 2012 Jun;36(6):843-54
pubmed: 21844879
Am J Physiol. 1991 Aug;261(2 Pt 2):R501-7
pubmed: 1877708
Diabetes Ther. 2020 Jun;11(6):1199-1216
pubmed: 32297119
Int J Obes Relat Metab Disord. 2001 Dec;25 Suppl 5:S42-7
pubmed: 11840214
J Clin Endocrinol Metab. 2003 Oct;88(10):4696-701
pubmed: 14557443
Diabetes Obes Metab. 2021 Jan;23(1):68-74
pubmed: 32886401
Lancet. 2017 Apr 8;389(10077):1399-1409
pubmed: 28237263
Int J Obes (Lond). 2016 Nov;40(11):1699-1706
pubmed: 27434221
Nat Rev Endocrinol. 2015 Jun;11(6):329-38
pubmed: 25850661
N Engl J Med. 2016 Jul 28;375(4):311-22
pubmed: 27295427
J Clin Endocrinol Metab. 2015 Feb;100(2):342-62
pubmed: 25590212
Nutrients. 2019 Nov 08;11(11):
pubmed: 31717265
Diabetes Obes Metab. 2018 Feb;20 Suppl 1:5-21
pubmed: 29364588
Nat Chem Biol. 2009 Oct;5(10):749-57
pubmed: 19597507
Nat Med. 2002 Jul;8(7):738-42
pubmed: 12068290
Nat Neurosci. 2005 May;8(5):551
pubmed: 15856060
J Clin Endocrinol Metab. 2015 Dec;100(12):4541-52
pubmed: 26445112
Hepatol Commun. 2020 Sep 01;4(11):1610-1623
pubmed: 33163832
Diabetologia. 2006 Aug;49(8):1915-23
pubmed: 16802131
Obes Rev. 2017 Jul;18(7):715-723
pubmed: 28489290
J Lipid Res. 1963 Apr;4:193-9
pubmed: 14168151
J Biol Chem. 2019 Mar 8;294(10):3514-3531
pubmed: 30622136
Trends Endocrinol Metab. 2020 Jun;31(6):410-421
pubmed: 32396843
Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E671-8
pubmed: 12626323
Obesity (Silver Spring). 2018 May;26(5):814-818
pubmed: 29626388
Front Physiol. 2019 Apr 24;10:413
pubmed: 31068828
Am J Physiol. 1993 Jan;264(1 Pt 2):R116-22
pubmed: 8430871
JAMA. 2021 Apr 13;325(14):1403-1413
pubmed: 33625476
Nature. 2001 Jan 11;409(6817):194-8
pubmed: 11196643
Lancet. 2021 Aug 14;398(10300):583-598
pubmed: 34370970
Rev Endocr Metab Disord. 2014 Sep;15(3):181-7
pubmed: 24811133
N Engl J Med. 1996 Feb 1;334(5):292-5
pubmed: 8532024
JAMA Cardiol. 2018 Apr 1;3(4):280-287
pubmed: 29490333
Diabetologia. 1996 Oct;39(10):1227-32
pubmed: 8897012
Physiol Behav. 1982 Feb;28(2):313-22
pubmed: 7079345