Effect of a glucagon receptor antibody (REMD-477) in type 1 diabetes: A randomized controlled trial.

Abstract

The aim of the current study (Clinical trial reg. no. NCT02715193, clinicaltrials.gov) was to study the efficacy and safety of REMD-477, a glucagon receptor antagonist, in type 1 diabetes. This was a randomized controlled trial in which 21 patients with type 1 diabetes were enrolled. Glycaemic control and insulin use were evaluated in outpatient and inpatient settings, before and after a single 70-mg dose of REMD-477 (half-life 7-10 days) or placebo. Inpatient insulin use was 26% (95% CI, 47%, 4%) lower 1 day after dosing with REMD-477 than with placebo (P = .02). Continuous glucose monitoring during post-treatment days 6 to 12 showed that average daily glucose was 27 mg/dL lower (P < .001), percent time-in-target-range (70-180 mg/dL) was ~25% greater (~3.5 h/d) (P = .001), and percent time-in-hyperglycaemic-range (> 180 mg/dL) was ~40% lower (~4 h/d) (P = .001) in the REMD-477 group than in the placebo group, without a difference in percent time-in-hypoglycaemic-range (<70 mg/dL). No serious adverse events were reported. Glucagon receptor antagonism decreases insulin requirements and improves glycaemic control in patients with type 1 diabetes.

• Authors: Jeremy Pettus, Dominic Reeds, Tricia S Cavaiola, Schafer Boeder, Michelle Levin, Garry Tobin, Edda Cava, Dung Thai, Jim Shi, Hai Yan, Edgar Bautista, John McMillan, Roger Unger, Robert R Henry, Samuel Klein
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 20 Issue 5 Pg. 1302-1305 (05 2018) ISSN: 1463-1326 [Electronic] England
• PMID: 29283470 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 John Wiley & Sons Ltd.

Chemical References

• Antibodies, Blocking
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Blood Glucose
• Drugs, Investigational
• Hypoglycemic Agents
• Insulin
• Receptors, Glucagon
• volagidemab

Topics

• Adult
• Antibodies, Blocking (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Blood Glucose (analysis)
• Diabetes Mellitus, Type 1 (blood, drug therapy, metabolism)
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination
• Drugs, Investigational (adverse effects, therapeutic use)
• Female
• Humans
• Hyperglycemia (prevention & control)
• Hypoglycemia (chemically induced, prevention & control)
• Hypoglycemic Agents (administration & dosage, adverse effects, therapeutic use)
• Injections, Subcutaneous
• Insulin (administration & dosage, therapeutic use)
• Male
• Monitoring, Ambulatory
• Proof of Concept Study
• Receptors, Glucagon (antagonists & inhibitors, metabolism)