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Glucagon receptor antagonists for diabetes mellitus treatment: A systematic literature review
Author(s) -
Miyama Kelle,
Elbarbry Fawzy,
Bzowyckyj Andrew
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.514.5
Subject(s) - glucagon receptor , medicine , diabetes mellitus , adverse effect , pharmacokinetics , glucagon , hypoglycemia , pharmacodynamics , glucagon like peptide 1 receptor , animal studies , pharmacology , agonist , endocrinology , antagonist , receptor , insulin
Objective The objective of the study was to evaluate the available literature on the safety and efficacy of glucagon receptor antagonists for the treatment of diabetes mellitus. Methods A search of PubMed using the terms “glucagon receptor antagonist AND diabetes” and “Pharmacokinetics AND pharmacodynamics AND glucagon receptor antagonist” was conducted. Initial study selection identified 398 articles. Titles and abstracts were reviewed for relevance, resulting in a total of 377 articles excluded (e.g. use of GLP‐1 or GIP agonist, combination therapy). The full texts of the remaining articles were evaluated and their references reviewed to identify additional articles meeting inclusion/exclusion criteria (n=2); resulting in 23 total studies included. Results Of the current literature evaluated, 13 studies were conducted in animal models, whereas 11 studies were conducted in humans, with one study occurring in both. A few compounds were identified as having promise for diabetes management including: LY2409021, LGD‐6972, REGN1193, Bay 27‐9955, PF‐06291874, MK‐3577. Findings from the animal and human studies were similar. Both study types demonstrated consistent glucose lowering effects with low rates of hypoglycemia, but varied by agent in regards to alterations in other surrogate measures (e.g. blood pressure, HDL‐C, LDL‐C, Triglycerides, AST, ALT), pharmacokinetics, and adverse effect patterns. Most adverse effects identified were minor and reversible. Efficacy of glucose lowering effects in animal models showed a reduction in blood glucose ranging in magnitude of 57–98 mg/dL. Human models demonstrated a lowering in FPG ranging in magnitude of 27–57 mg/dL. Conclusion Glucagon receptor antagonists have shown promise in animal and human models as an alternative option for diabetes mellitus treatment. The glucose lowering benefit with low rates of hypoglycemia is promising. Ongoing research is needed to further assess their efficacy and safety over the long‐term. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .