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

Diabetes Obes Metab. 2018 May;20(5):1302-1305. doi: 10.1111/dom.13202. Epub 2018 Jan 22.

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.

Keywords: diabetes; glucose homeostasis; glycaemic control, insulin.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • 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
  • Female
  • 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 / administration & dosage*
  • Insulin / therapeutic use
  • Male
  • Monitoring, Ambulatory
  • Proof of Concept Study
  • Receptors, Glucagon / antagonists & inhibitors*
  • Receptors, Glucagon / metabolism

Substances

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

Associated data

  • ClinicalTrials.gov/NCT02715193