volagidemab (REMD-477) / Amgen, REMD Bio - LARVOL DELTA

The Role of Glucagon in Glucose Metabolism in Humans With and Without Bariatric Surgery (clinicaltrials.gov) - P1 | N=150 | Not yet recruiting | Sponsor: The University of Texas Health Science Center at San Antonio

New P1 trial

Glucagon Antagonism Improves Insulin Sensitivity and Increases Lean Body Mass in Patients with Type 1 Diabetes—A Twelve-Week Double-Blind, Randomized, Placebo-Controlled Trial (ADA 2025) - "This study aimed to assess the comprehensive metabolic effects of glucagon antagonism in type 1 diabetes (T1D). 30 adults with T1D were randomized 1:1 to receive the glucagon receptor antagonist (GRA) volagidemab via once weekly subq injection for 12 weeks vs. placebo... GRA therapy decreased lipolysis, improved peripheral glucose disposal, increased glucose oxidation, and increased lean body mass. These data highlight the profound effects that glucagon action has on multiple aspects of metabolism that extend far beyond glucose control."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Glucagon Receptor Blockade REMD-77 Further Improves Fasting Hyperglycaemia after Bariatric Surgery, But Reduces Hepatic Fatty Acid Oxidation (ADA 2025) - "The effects of GCGR antagonists and GB on glycaemic improvement appear to be synergistic without compromising the glycemic effect of glucagon rescue. However, single dose of REMD-477 decreased hepatic fatty acid oxidation increasing the risk of steatosis."

Bariatric surgery • Surgery • Diabetes • Metabolic Disorders • Obesity

Effects of GRA in Patients With Type 1 (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: University of California, San Diego | Trial completion date: Mar 2025 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Jul 2024

Trial completion date • Trial primary completion date • Cardiovascular • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Glucagon Rescue of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes Treated With Volagidemab (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: REMD Biotherapeutics, Inc. | Recruiting ➔ Completed | Trial completion date: Jun 2025 ➔ Feb 2025 | Trial primary completion date: Jun 2025 ➔ Feb 2025

Trial completion • Trial completion date • Trial primary completion date • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Efficacy and safety of the glucagon receptor antagonist volagidemab in type-1 diabetes: A systematic review and meta-analysis. (PubMed, Ann N Y Acad Sci) - "Occurrence of treatment-emergent adverse events (odds ratio [OR]: 0.96 (95% CI: [0.36, 2.56]); I2 = 8%; p = 0.94) and hypoglycemia (OR: 0.56 (95% CI: [0.11, 2.89]); I2 = 0%; p = 0.49) were similar among volagidemab users as compared to placebo. Short-term volagidemab use was associated with significant reduction in insulin requirement along with improvement in glycemia."

Journal • Retrospective data • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

SOTA: Combination Adjunctive Therapy to Address Multiple Metabolic Imbalances in Type 1 Diabetes (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: University of California, San Diego | Not yet recruiting ➔ Recruiting | Trial completion date: Jan 2026 ➔ Jan 2028 | Trial primary completion date: Jan 2026 ➔ Jan 2028

Enrollment open • Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Blocking glucagon receptor improves hyperglycaemia to larger extent after bariatric surgery (EASD 2024) - "Here, we aim to investigate the glycemic effect of GCGR blockade using REMD-477, a human GR monoclonal antibody in diet-induced obese rats treated with GB... These results offer valuable insights into the synergistic therapeutic effects of GCGR antagonism and bariatric surgery on glycemic improvement without compromising the glycemic effect of glucagon rescue injection. Further exploration of the underlying mechanisms by which bariatric surgery alters glucagon signal is warranted."

Bariatric surgery • Surgery • Diabetes • Metabolic Disorders • Obesity

Effect of Novel Glucagon Receptor Antagonist REMD-477 on Glucose and Adipocyte Metabolism in T2DM (clinicaltrials.gov) - P1 | N=4 | Completed | Sponsor: The University of Texas Health Science Center at San Antonio | Suspended ➔ Completed | N=24 ➔ 4

Enrollment change • Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Combination SGLT2 Inhibitor and Glucagon Receptor Antagonist Therapy in Type 1 Diabetes: A Randomized Clinical Trial. (PubMed, Diabetes Care) - "Glucagon antagonism enhances the therapeutic effects of SGLT2 inhibition in type 1 diabetes. Combination therapy improves glycemic control, reduces insulin dosing, and suggests a strategy to unlock the benefits of SGLT2 inhibitors while mitigating the risk of diabetic ketoacidosis."

Clinical • Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Effect of Novel Glucagon Receptor Antagonist REMD-477 on Glucose and Adipocyte Metabolism in T2DM (clinicaltrials.gov) - P1 | N=24 | Suspended | Sponsor: The University of Texas Health Science Center at San Antonio | Recruiting ➔ Suspended

Trial suspension • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Glucagon Rescue of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes Treated With Volagidemab (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: REMD Biotherapeutics, Inc.

New P1 trial • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Effects of GRA in Patients With Type 1 (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: University of California, San Diego | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • ICAM3 • VCAM1

ADA Presidents' Select Abstract: Combining an SGLT Inhibitor with a Glucagon Receptor Antagonist (GRA) in Subjects with Type 1 Diabetes—A Randomized Clinical Trial (ADA 2023) - "Combination therapy (SGLTi + GRA) could augment glycemic and insulin dosing benefits while mitigating DKA risk.Subjects with T1D (n=12) received 4-week insulin-adjunctive treatments with (a) SGLTi (dapagliflozin 10 mg) + placebo and (b) SGLTi + GRA (volagidemab 70 mg) in a cross-over, double-blind design. Peak beta-hydroxybutyrate (BHB) concentrations during IWT were lower with SGLTi + GRA treatment (2.03 mmol/L) than with SGLTi alone (2.44 mmol/L; P = 0.04); there was no significant difference in peak BHB with either treatment vs Baseline (2.14 mmol/L).Treatment with SGLTi + GRA improved glycemic control, reduced insulin use, and mitigated ketosis during hypoinsulinemia. These data suggest that combination adjunctive therapy may be effective to address multiple metabolic abnormalities in T1D."

Clinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Emerging Anti-Diabetic Drugs for Beta-Cell Protection in Type 1 Diabetes. (PubMed, Cells) - "Many investigational new drugs fall under the category of immunomodulators, such as the recently FDA-approved CD-3 monoclonal antibody teplizumab. Specifically, we discuss several non-immunomodulators that may have more direct action on beta cells, such as verapamil (a voltage-dependent calcium channel blocker), gamma aminobutyric acid (GABA, a major neurotransmitter with effects on beta cells), tauroursodeoxycholic acid (TUDCA, an endoplasmic reticulum chaperone), and volagidemab (a glucagon receptor antagonist). These emerging anti-diabetic drugs are expected to provide promising results in both beta-cell restoration and in suppressing cytokine-derived inflammation."

Journal • Review • Diabetes • Immune Modulation • Immunology • Inflammation • Metabolic Disorders • Type 1 Diabetes Mellitus

Publisher Correction: Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial. (PubMed, Nat Med) - No abstract available

Clinical • P2 data • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Effect of Novel Glucagon Receptor Antagonist REMD-477 on Glucose and Adipocyte Metabolism in T2DM (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: The University of Texas Health Science Center at San Antonio | Trial completion date: Nov 2024 ➔ Nov 2025 | Trial primary completion date: Nov 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

SOTA: Combination Adjunctive Therapy to Address Multiple Metabolic Imbalances in Type 1 Diabetes (clinicaltrials.gov) - P1/2 | N=22 | Not yet recruiting | Sponsor: University of California, San Diego

New P1/2 trial • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Combination GRA and SGLT-2i Treatment in Type 1 Diabetes (clinicaltrials.gov) - P1/2 | N=12 | Completed | Sponsor: University of California, San Diego | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Glucagon Receptor Inhibition to Enable Breast Cancer Patients to Benefit From PI3K Inhibitor Therapy (REMD-477) (clinicaltrials.gov) - P1 | N=1 | Terminated | Sponsor: Duke University | Recruiting ➔ Terminated; Lack of enrollment

Trial termination • Breast Cancer • Diabetes • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial. (PubMed, Nat Med) - "No increase in hypoglycemia was observed with volagidemab therapy; however, increases in serum transaminases, low-density lipoprotein (LDL)-cholesterol and blood pressure were observed. Although the primary endpoint did not meet the prespecified significance level, we believe that the observed reduction in HbA1c and tolerable safety profile provide a rationale for further randomized studies to define the long-term efficacy and safety of volagidemab in patients with T1D."

Clinical • Journal • P2 data • Diabetes • Dyslipidemia • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Combination GRA and SGLT-2i Treatment in Type 1 Diabetes (clinicaltrials.gov) - P1/2 | N=12 | Active, not recruiting | Sponsor: University of California, San Diego | Trial completion date: May 2022 ➔ Oct 2022

Trial completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Metabolic Pathways of GRA in Patients With Type 1 Diabetes (clinicaltrials.gov) - P1/2 | N=4 | Completed | Sponsor: University of California, San Diego | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Metabolic Pathways of GRA in Patients With Type 1 Diabetes (clinicaltrials.gov) - P1/2 | N=4 | Active, not recruiting | Sponsor: University of California, San Diego | Trial completion date: Oct 2021 ➔ May 2022

Trial completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Combination GRA and SGLT-2i Treatment in Type 1 Diabetes (clinicaltrials.gov) - P1/2 | N=12 | Active, not recruiting | Sponsor: University of California, San Diego | Trial completion date: Jan 2022 ➔ May 2022

Trial completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus