Related Experiment Video
Updated: Jul 7, 2026

An In Ovo Model for Testing Insulin-mimetic Compounds
Published on: April 23, 2018
Small molecule glucagon receptor antagonists: an updated patent review (2015-2019)
Chen Cheng1, Salman Jabri1, Brandon M Taoka1
1Merck & Co., Inc , South San Francisco, California, USA (MSD).
Introduction:
The peptide hormone glucagon acts as a counterregulatory response to hypoglycemia and as a key driver in the development of all forms of diabetes. Thus, inhibition of glucagon action, including through antagonism of the glucagon receptor by small molecule therapeutics, has been explored in clinical settings as a means to achieve glycemic control in patients with type 2 diabetes mellitus and mitigate associated comorbidities.
Areas Covered:
This review covers patent applications concerning small molecule glucagon receptor antagonists (GRAs) published between 2015 and 2019. With the exception of the cholesterol absorption inhibitor-GRA combination, patents, or applications pertaining to combination therapies or method of treatment were excluded. In addition, a discussion on findings from clinical trials is included.
Expert Opinion:
An evident trend toward declining discovery efforts in GRAs was observed. With respect to the structural novelty, most applications contain compounds broadly similar to earlier chemical matter. Based on findings from clinical trials, while GRAs are highly effective in lowering hemoglobin A1c (HbA1c) levels, key safety issues (cholesterol elevation, aminotransferase elevation, blood pressure effects) remain the primary hurdle for the field.
Related Concept Videos
Oral Hypoglycemic Agents: Biguanides and Glitazones
Oral Hypoglycemic Agents: Glinides
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
Acarbose and miglitol are typically...
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
Dipeptidyl Peptidase 4 Inhibitors
Hypoglycemia and Glucagon

