ArticleDiabetes, obesity & metabolism2017
Pharmacokinetics and pharmacodynamics of single and multiple doses of the glucagon receptor antagonist LGD-6972 in healthy subjects and subjects with type 2 diabetes mellitus.
Article in Diabetes, obesity & metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 49 citations in OpenAlex.
- Trial
- A first-in-human pharmacodynamic and pharmacokinetic study of a fully human anti-glucagon receptor monoclonal antibody in normal healthy volunteers.Diabetes, obesity & metabolism · 2018Trial
- Cyclodextrin-based therapeutics delivery systems: A review of current clinical trials.Current research in pharmacology and drug discovery · 2025Review
- The Inferential Binding Sites of GCGR for Small Molecules Using Protein Dynamic Conformations and Crystal Structures.International journal of molecular sciences · 2024Article
- Novel time-resolved reporter mouse reveals spatial and transcriptional heterogeneity during alpha cell differentiation.Diabetologia · 2024Article
- The role of glucagon after bariatric/metabolic surgery: much more than an "anti-insulin" hormone.Frontiers in endocrinology · 2023Review
- The past, present, and future physiology and pharmacology of glucagon.Cell metabolism · 2022Review
- Glucagon receptor signaling at white adipose tissue does not regulate lipolysis.American journal of physiology. Endocrinology and metabolism · 2022Article
- Review
- The incretin/glucagon system as a target for pharmacotherapy of obesity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022 · on this mapReview
- Role of Glucagon and Its Receptor in the Pathogenesis of Diabetes.Frontiers in endocrinology · 2022Review
- Synthesis and anti-diabetic activity of novel biphenylsulfonamides as glucagon receptor antagonists.Chemical biology & drug design · 2021Article
- Novel therapies with precision mechanisms for type 2 diabetes mellitus.Nature reviews. Endocrinology · 2021Review
- Glucagon's Metabolic Action in Health and Disease.Comprehensive Physiology · 2021Article
- Therapeutics for type-2 diabetes mellitus: a glance at the recent inclusions and novel agents under development for use in clinical practice.Therapeutic advances in endocrinology and metabolism · 2021Review
- The Vicious Circle of Hepatic Glucagon Resistance in Non-Alcoholic Fatty Liver Disease.Journal of clinical medicine · 2020Review
- Obesity dysregulates fasting-induced changes in glucagon secretion.The Journal of endocrinology · 2019Article
- [Incretin-based co- and tri-agonists : Innovative polypharmacology for the treatment of obesity and diabetes].Der Internist · 2019Review
- Antagonistic Glucagon Receptor Antibody Promotes α-Cell Proliferation and Increases β-Cell Mass in Diabetic Mice.iScience · 2019Article
- Glucagon Receptor Signaling and Lipid Metabolism.Frontiers in physiology · 2019Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of a novel, oral glucagon receptor antagonist, LGD-6972, in healthy subjects and subjects with type 2 diabetes (T2DM).
methodsIn the single ascending dose study, LGD-6972 (2-480 mg) was administered to healthy subjects (n = 48) and T2DM subjects (n = 8). In the multiple ascending dose study, healthy subjects (n = 12) received a dose of 15 mg LGD-6972 and T2DM subjects (n = 36) received doses of 5, 10 or 15 mg of LGD-6972 daily for 14 days.
resultsLGD-6972 had linear plasma pharmacokinetics consistent with once-daily dosing that was comparable in healthy and T2DM subjects. Dose-dependent decreases in fasting plasma glucose were observed in all groups with a maximum of 3.15 mmol/L (56.8 mg/dL) on day 14 in T2DM subjects. LGD-6972 also reduced plasma glucose in the postprandial state. Dose-dependent increases in fasting plasma glucagon were observed, but glucagon levels decreased and insulin levels increased after an oral glucose load in T2DM subjects. LGD-6972 was well tolerated at the doses tested without dose-related or clinically meaningful changes in clinical laboratory parameters. No subject experienced hypoglycaemia.
conclusionInhibition of glucagon action by LGD-6972 was associated with decreases in glucose in both healthy and T2DM subjects, the magnitude of which was sufficient to predict improvement in glycaemic control with longer treatment duration in T2DM patients. The safety and pharmacological profile of LGD-6972 after 14 days of dosing supports continued clinical development.
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