Investigational glucagon receptor antagonists in Phase I and II clinical trials for diabetes

Insulin and Glucagon: Partners for Life

(2017) Jens Juul Holst et al.   ENDOCRINOLOGY

Population pharmacokinetics and pharmacodynamics of IONIS-GCGRRx, an antisense oligonucleotide for type 2 diabetes mellitus: a red blood cell lifespan model

(2017) Kenneth T. Luu et al.   JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS

The New Biology and Pharmacology of Glucagon

(2017) T. D. Müller et al.   PHYSIOLOGICAL REVIEWS

Glucagon receptor inhibition normalizes blood glucose in severe insulin-resistant mice

(2017) Haruka Okamoto et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Glucagon antagonism in islet cell proliferation

(2017) E. Danielle Dean et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Response to Comment on The Look AHEAD Research Group. Prospective Association of GLUL rs10911021 With Cardiovascular Morbidity and Mortality Among Individuals With Type 2 Diabetes: The Look AHEAD Study. Diabetes 2016;65:297–302

(2016) Jeanne M. McCaffery et al.   DIABETES

Clinical Trials, Triumphs, and Tribulations of Glucagon Receptor Antagonists

(2016) Mackenzie J. Pearson et al.   DIABETES CARE

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

(2016) Eric G. Vajda et al.   DIABETES OBESITY & METABOLISM

Effects of multiple ascending doses of the glucagon receptor antagonist PF-06291874 in patients with type 2 diabetes mellitus

(2016) D. J. Kazierad et al.   DIABETES OBESITY & METABOLISM

Robust anti-obesity and metabolic effects of a dual GLP-1/glucagon receptor peptide agonist in rodents and non-human primates

(2016) S. J. Henderson et al.   DIABETES OBESITY & METABOLISM

Glucagon therapeutics: Dawn of a new era for diabetes care

(2016) Jaime A. Davidson et al.   DIABETES-METABOLISM RESEARCH AND REVIEWS

Glucagon action in the brain

(2016) Mona A. Abraham et al.   DIABETOLOGIA

Glucagon is the key factor in the development of diabetes

(2016) Young H. Lee et al.   DIABETOLOGIA

THE ROLE OF GLUCAGON IN THE PATHOPHYSIOLOGY AND MANAGEMENT OF DIABETES

(2016) Georgia R. Kulina et al.   Endocrine Practice

Investigational insulin secretagogues for type 2 diabetes

(2016) André J. Scheen   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist

(2016) Nicolas Damond et al.   eLife

Future glucose-lowering drugs for type 2 diabetes

(2016) Clifford J Bailey et al.   Lancet Diabetes & Endocrinology

Glucagon receptor gene deletion in insulin knockout mice modestly reduces blood glucose and ketones but does not promote survival

(2016) Ursula H. Neumann et al.   Molecular Metabolism

Landmark studies on the glucagon subfamily of GPCRs: from small molecule modulators to a crystal structure

(2015) De-hua Yang et al.   ACTA PHARMACOLOGICA SINICA

Recent progress in the development of small-molecule glucagon receptor antagonists

(2015) Matthew F. Sammons et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Evaluation of Efficacy and Safety of the Glucagon Receptor Antagonist LY2409021 in Patients With Type 2 Diabetes: 12- and 24-Week Phase 2 Studies

(2015) Christof M. Kazda et al.   DIABETES CARE

Short-term administration of the glucagon receptor antagonist LY2409021 lowers blood glucose in healthy people and in those with type 2 diabetes

(2015) R. P. Kelly et al.   DIABETES OBESITY & METABOLISM

Inhibiting or antagonizing glucagon: making progress in diabetes care

(2015) P. J. Lefèbvre et al.   DIABETES OBESITY & METABOLISM

Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes

(2015) Vivi R. Steenberg et al.   DIABETOLOGIA

Glucagon Receptor Blockade With a Human Antibody Normalizes Blood Glucose in Diabetic Mice and Monkeys

(2015) Haruka Okamoto et al.   ENDOCRINOLOGY

Discontinued drug therapies to treat diabetes in 2014

(2015) Jerry R Colca   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Small molecule glucagon receptor antagonists: a patent review (2011 – 2014)

(2015) Kevin J Filipski   EXPERT OPINION ON THERAPEUTIC PATENTS

Glucagon Cell Hyperplasia and Neoplasia With and Without Glucagon Receptor Mutations

(2015) Bence Sipos et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Lack of glucagon receptor signaling and its implications beyond glucose homeostasis

(2015) M. J. Charron et al.   JOURNAL OF ENDOCRINOLOGY

Glucagon receptor antagonism induces increased cholesterol absorption

(2015) Hong-Ping Guan et al.   JOURNAL OF LIPID RESEARCH

A new paradigm for treating obesity and diabetes mellitus

(2015) André J. Scheen et al.   Nature Reviews Endocrinology

Islet α cells and glucagon—critical regulators of energy homeostasis

(2015) Jonathan E. Campbell et al.   Nature Reviews Endocrinology

Glucagon – Early breakthroughs and recent discoveries

(2015) Bo Ahrén   PEPTIDES

Glucagon receptor antibody completely suppresses type 1 diabetes phenotype without insulin by disrupting a novel diabetogenic pathway

(2015) May-Yun Wang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Semi-mechanistic Model for the Effects of a Novel Glucagon Receptor Antagonist on Glucagon and the Interaction Between Glucose, Glucagon, and Insulin Applied to Adaptive Phase II Design

(2014) Joanna Z. Peng et al.   AAPS Journal

Two novel glucagon receptor antagonists prove effective therapeutic agents in high-fat-fed and obese diabetic mice

(2014) F. P. M. O'Harte et al.   DIABETES OBESITY & METABOLISM

Pharmacodynamics, Efficacy and Safety of Sodium–Glucose Co-Transporter Type 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes Mellitus

(2014) André J. Scheen   DRUGS

Characterization of a Standardized Glucagon Challenge Test as a Pharmacodynamic Tool in Pharmacological Research

(2014) M.G. van Dongen et al.   HORMONE AND METABOLIC RESEARCH

First proof of pharmacology in humans of a novel glucagon receptor antisense drug

(2014) Marloes G. J. van Dongen et al.   JOURNAL OF CLINICAL PHARMACOLOGY

Ablation of glucagon receptor signaling by peptide-based glucagon antagonists improves glucose tolerance in high fat fed mice

(2014) Laura M. McShane et al.   PEPTIDES

The design and synthesis of a potent glucagon receptor antagonist with favorable physicochemical and pharmacokinetic properties as a candidate for the treatment of type 2 diabetes mellitus

(2013) Angel Guzman-Perez et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Fibroblast Growth Factor 21 (FGF21) and Glucagon-Like Peptide 1 Contribute to Diabetes Resistance in Glucagon Receptor-Deficient Mice

(2013) B. A. Omar et al.   DIABETES

Pancreatic α-Cell Hyperplasia: Facts and Myths

(2013) Run Yu   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Characterisation of structurally modified analogues of glucagon as potential glucagon receptor antagonists

(2013) F.P.M. O’Harte et al.   MOLECULAR AND CELLULAR ENDOCRINOLOGY

Structure of the human glucagon class B G-protein-coupled receptor

(2013) Fai Yiu Siu et al.   NATURE

Expression, purification and preliminary characterization of glucagon receptor extracellular domain

(2013) Lili Wu et al.   PROTEIN EXPRESSION AND PURIFICATION

Liver-Specific Disruption of the Murine Glucagon Receptor Produces  -Cell Hyperplasia: Evidence for a Circulating  -Cell Growth Factor

(2012) C. Longuet et al.   DIABETES

Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover

(2012) Roger H. Unger et al.   JOURNAL OF CLINICAL INVESTIGATION

Discovery of a Novel Glucagon Receptor Antagonist N-[(4-{(1S)-1-[3-(3, 5-Dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine (MK-0893) for the Treatment of Type II Diabetes

(2012) Yusheng Xiong et al.   JOURNAL OF MEDICINAL CHEMISTRY

Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR) knockout mice: implications on anti-glucagon therapies for diabetes

(2011) Jianxin Yang et al.   BMC GENOMICS

Hepatic Glucagon Action Is Essential for Exercise-Induced Reversal of Mouse Fatty Liver

(2011) Eric D. Berglund et al.   DIABETES

Novel insight into glucagon receptor action: lessons from knockout and transgenic mouse models

(2011) P. M. Vuguin et al.   DIABETES OBESITY & METABOLISM

Early milestones in glucagon research

(2011) P. J. Lefèbvre   DIABETES OBESITY & METABOLISM

Glucagon antagonism as a potential therapeutic target in type 2 diabetes

(2011) J. I. Bagger et al.   DIABETES OBESITY & METABOLISM

Chronic treatment with a glucagon receptor antagonist lowers glucose and moderately raises circulating glucagon and glucagon-like peptide 1 without severe alpha cell hypertrophy in diet-induced obese mice

(2011) J. Mu et al.   DIABETOLOGIA

A survey of small molecule glucagon receptor antagonists from recent patents (2006 – 2010)

(2011) Dong-Ming Shen et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Dual elimination of the glucagon and GLP-1 receptors in mice reveals plasticity in the incretin axis

(2011) Safina Ali et al.   JOURNAL OF CLINICAL INVESTIGATION

Fully Human Monoclonal Antibodies Antagonizing the Glucagon Receptor Improve Glucose Homeostasis in Mice and Monkeys

(2009) H. Yan et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Long-Term Inhibition of the Glucagon Receptor with a Monoclonal Antibody in Mice Causes Sustained Improvement in Glycemic Control, with Reversible  -Cell Hyperplasia and Hyperglucagonemia

(2009) W. Gu et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Homozygous P86S Mutation of the Human Glucagon Receptor Is Associated With Hyperglucagonemia, α Cell Hyperplasia, and Islet Cell Tumor

(2009) Cuiqi Zhou et al.   PANCREAS

Benefits and limitations of reducing glucagon action for the treatment of type 2 diabetes

(2008) Safina Ali et al.   AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting

(2008) Christine Longuet et al.   Cell Metabolism