scholarly journals Small Molecule Drug Discovery at the Glucagon-Like Peptide-1 Receptor

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Francis S. Willard ◽  
Ana B. Bueno ◽  
Kyle W. Sloop
Keyword(s):  
Drug Discovery ◽  
Small Molecule ◽  
Receptor Ligands ◽  
Therapeutic Success ◽  
Receptor Agonists ◽  
Screening Strategies ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Nonpeptide Ligands

The therapeutic success of peptide glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus has inspired discovery efforts aimed at developing orally available small molecule GLP-1 receptor agonists. Although the GLP-1 receptor is a member of the structurally complex class B1 family of GPCRs, in recent years, a diverse array of orthosteric and allosteric nonpeptide ligands has been reported. These compounds include antagonists, agonists, and positive allosteric modulators with intrinsic efficacy. In this paper, a comprehensive review of currently disclosed small molecule GLP-1 receptor ligands is presented. In addition, examples of “ligand bias” and “probe dependency” for the GLP-1 receptor are discussed; these emerging concepts may influence further optimization of known molecules or persuade designs of expanded screening strategies to identify novel chemical starting points for GLP-1 receptor drug discovery.

Patient-Reported Outcomes following Initiation of Glucagon-Like Peptide-1 Receptor AgonistS (GLP–1RA) in PatientS with Type 2 Diabetes—PROGRESS-DIABETES Study

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1096-P
Author(s):  
RUTH E. BROWN ◽  
ALEXANDER ABITBOL ◽  
HARPREET S. BAJAJ ◽  
HASNAIN KHANDWALA ◽  
RONALD GOLDENBERG ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Patient Reported Outcomes ◽  
Receptor Agonists ◽  
Patient Reported ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

1019-P: Glucagon-Like Peptide-1 Receptor Agonists Predominantly Reduce Body Fat Mass in Patients with Type 2 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1019-P
Author(s):  
YUKI FUJITA ◽  
SODAI KUBOTA ◽  
HITOSHI KUWATA ◽  
DAISUKE YABE ◽  
YOSHIYUKI HAMAMOTO ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Fat ◽  
Fat Mass ◽  
Body Fat Mass ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 agonist therapy in patients with diabetes mellitus and obesity

2020 ◽  
Vol 98 (3) ◽  
pp. 210-217
Author(s):  
A. Yu. Babenko ◽  
Yu. A. Kononova ◽  
M. V. Martjanova ◽  
A. V. Simanenkova ◽  
M. A. Kokina ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Hba1c Level ◽  
High Efficiency ◽  
Receptor Agonists ◽  
Predictors Of Response ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Lipids Metabolism

Due to the high efficiency of glucagon-like peptide-1 (GLP-1) receptor agonists therapy in only a part of patients, the search for predictors of response to the treatment is a relevant problem. Purpose. The purpose is to compare the efficacy of liraglutide and exenatide therapy in obese patients with type 2 diabetes mellitus (T2DM) and to evaluate the predictors of response to glycated hemoglobin (HbA1c), weight and lipids reduction. Material and methods. The study included 47 patients with type 2 diabetes and obesity who received GLP-1 receptor agonists therapy. 26 patients were treated with liraglutide, 21 patients were treated with exenatide. We measured the parameters of carbohydrate and lipid metabolism, the levels of hormones involved in glucose and lipids metabolism and in appetite regulation. Blood pressure was measured. These parameters were evaluated at baseline and after 24 weeks of treatment. Results. Patients receiving exenatide therapy showed a tendency towards more frequent HbA1c level reduction by 1% or more (60% versus 30.4%, p = 0.07). The effects of liraglutide and exenatide on weight and waist circumference were comparable. When assessing the predictors of response to the therapy, a more pronounced decrease in HbA1c level (by 1% or more) was in the patients with a higher initial HbA1c level (8.7 (8.2; 9.7) versus 8.2 (6.9; 8.7)%, p = 0.04), as well as with a higher initial GLP-1 level (0.12 (0.05; 0.17) versus 0.040 (0.01; 0.09) ng/ml.) A more significant decrease in the triglycerides (TG) level was detected in patients with a higher level of glucose-dependent insulinotropic peptide (GIP) before therapy (409 (316.0; 431.4) pg/ml in patients who reduced TG level by 30% or more and 331.5 (324.9; 367.1) pg/ml in patients with a lower decrease in TG level). Among the studied parameters, no predictors of body mass reduction were revealed. Conclusion. Measurement of HbA1c, GLP-1, GIP level may be useful to predict the efficacy of GLP-1 receptor agonists therapy.

Sign in / Sign up

Export Citation Format

Share Document