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

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2018-05, Vol.20 (5), p.1302-1305
• Main Authors: Pettus, Jeremy, Reeds, Dominic, Cavaiola, Tricia S., Boeder, Schafer, Levin, Michelle, Tobin, Garry, Cava, Edda, Thai, Dung, Shi, Jim, Yan, Hai, Bautista, Edgar, McMillan, John, Unger, Roger, Henry, Robert R., Klein, Samuel
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Blocking - administration & dosage; Antibodies, Blocking - adverse effects; Antibodies, Blocking - therapeutic use; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Blood Glucose - analysis; Clinical trials; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - metabolism; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Drugs, Investigational - adverse effects; Drugs, Investigational - therapeutic use; Evidence-based medicine; Female; Glucagon; glucose homeostasis; Glucose monitoring; glycaemic control, insulin; Humans; Hyperglycemia - prevention & control; Hypoglycemia - chemically induced; Hypoglycemia - prevention & control; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Injections, Subcutaneous; Insulin; Insulin - administration & dosage; Insulin - therapeutic use; Male; Monitoring, Ambulatory; Patients; Proof of Concept Study; Receptors, Glucagon - antagonists & inhibitors; Receptors, Glucagon - metabolism
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.13202

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 (