crotedumab (REGN1193) / Regeneron - LARVOL DELTA

Activating and Disrupting the Liver–Alpha-Cell Axis Respectively Enhances and Impairs Amino Acid Metabolism and Alpha-Cell Growth (ADA 2022) - "Female C57Bl/6JRj mice were treated with a long-acting glucagon analogue (GCGA, NNC9204-0043, Novo Nordisk A/S) or PBS twice daily, or once weekly with a GCGR antibody (GCGR Ab, REGN1193, Regeneron) or control antibody (Ctl...Thus, chronically increased GCGR signaling leads to hypoaminoacidemia and decreased alpha cell mass, while chronically decreased GCGR signaling leads to hyperaminoacidemia and increased alpha cell mass. These changes must be considered when developing glucagon-based therapeutics."

Late-breaking abstract • Diabetes • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Type 2 Diabetes Mellitus • ASS1

Increased and Decreased Glucagon Receptor Signaling Respectively Enhances and Impairs Triglyceride Metabolism Acutely and Chronically (ADA 2022) - "We investigated the effects of chronic GCGR inhibition and activation on plasma TG and cholesterol levels during an 180 min oral lipid tolerance test (10 µL/g body weight olive oil; OLTT) in GCGR knockout (Gcgr-/-) mice, and in C57Bl/6JRj mice treated with a GCGR antibody (GCGR Ab, REGN1193, Regeneron) or a long-acting glucagon analogue (GCGA, NNC9204-0043, Novo Nordisk A/S)...We were unable to identify GCGR in adipocytes using autoradiography and immunohistochemistry and our data thus implicate that glucagon has acute and chronic effects on intestinal lipid uptake and/or acts to enhance hepatic lipid metabolism in mice. Thus, impaired actions of glucagon may cause hypertriglyceridemia, while enhancing GCGR signaling may benefit subjects with dyslipidemia."

Diabetes • Hypertriglyceridemia • Metabolic Disorders • Type 2 Diabetes Mellitus