PMID- 32219200
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2575-9108 (Electronic)
IS  - 2575-9108 (Linking)
VI  - 1
IP  - 1
DP  - 2018 Sep 14
TI  - Beyond Glucagon-like Peptide-1: Is G-Protein Coupled Receptor Polypharmacology 
      the Path Forward to Treating Metabolic Diseases?
PG  - 3-11
LID - 10.1021/acsptsci.8b00009 [doi]
AB  - The glucagon-like peptide-1 receptor (GLP-1R) is a class B G-protein coupled 
      receptor (GPCR) that has proven to be an effective target for developing 
      medicines that treat type 2 diabetes mellitus (T2DM). GLP-1R agonists improve 
      T2DM by enhancing glucose-stimulated insulin secretion, delaying gastric transit, 
      decreasing glucagon levels, and reducing body weight due to anorexigenic actions. 
      The therapeutic successes of these agents helped inspire the design of new 
      multifunctional molecules that are GLP-1R agonists but also activate receptors 
      linked to pathways that enhance insulin sensitization and/or energy expenditure. 
      Herein, these agents are discussed in the context of polypharmacological 
      approaches that may enable even further improvement in treatment outcomes. 
      Moreover, we revisit classical polypharmaceutical GPCR approaches and how they 
      may be utilized for treatment of T2DM. To determine optimal combination regimens, 
      changes in drug discovery practices are likely needed because compensatory 
      mechanisms appear to underlie progression of T2DM and limit the ability of 
      current therapies to induce disease regression or remission.
CI  - Copyright (c) 2018 American Chemical Society.
FAU - Sloop, Kyle W
AU  - Sloop KW
AD  - Diabetes and Complications and Quantitative Biology, Lilly Research Laboratories, 
      Eli Lilly and Company, Indianapolis, Indiana 46285, United States.
FAU - Briere, Daniel A
AU  - Briere DA
AD  - Diabetes and Complications and Quantitative Biology, Lilly Research Laboratories, 
      Eli Lilly and Company, Indianapolis, Indiana 46285, United States.
FAU - Emmerson, Paul J
AU  - Emmerson PJ
AD  - Diabetes and Complications and Quantitative Biology, Lilly Research Laboratories, 
      Eli Lilly and Company, Indianapolis, Indiana 46285, United States.
FAU - Willard, Francis S
AU  - Willard FS
AD  - Diabetes and Complications and Quantitative Biology, Lilly Research Laboratories, 
      Eli Lilly and Company, Indianapolis, Indiana 46285, United States.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180628
PL  - United States
TA  - ACS Pharmacol Transl Sci
JT  - ACS pharmacology & translational science
JID - 101721411
PMC - PMC7088942
COIS- The authors declare the following competing financial interest(s): All authors 
      are employees of Eli Lilly and Company and may own company stock or possess stock 
      options.
EDAT- 2018/06/28 00:00
MHDA- 2018/06/28 00:01
PMCR- 2019/06/28
CRDT- 2020/03/29 06:00
PHST- 2018/04/24 00:00 [received]
PHST- 2020/03/29 06:00 [entrez]
PHST- 2018/06/28 00:00 [pubmed]
PHST- 2018/06/28 00:01 [medline]
PHST- 2019/06/28 00:00 [pmc-release]
AID - 10.1021/acsptsci.8b00009 [doi]
PST - epublish
SO  - ACS Pharmacol Transl Sci. 2018 Jun 28;1(1):3-11. doi: 10.1021/acsptsci.8b00009. 
      eCollection 2018 Sep 14.