Effect of a glucagon receptor antibody (REMD-477) in type 1 diabetes: A randomized controlled trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 29283470 · doi:10.1111/dom.13202
What was done
In a randomized controlled trial (NCT02715193), 21 patients with type 1 diabetes were enrolled to evaluate the efficacy and safety of REMD-477, a glucagon receptor antagonist. 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, including continuous glucose monitoring during post-treatment days 6 to 12.
What was found
Inpatient insulin use was 26% lower (95% CI, 47%, 4%; P = .02) 1 day after dosing with REMD-477 compared with placebo. 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 placebo. There was no difference in percent time-in-hypoglycaemic-range (<70 mg/dL). No serious adverse events were reported.
Why it matters
This study provides clinical proof-of-concept that glucagon receptor blockade can lower insulin requirements and improve glycaemic control without increasing hypoglycemia in type 1 diabetes.
Limits
The study is limited by a very small sample size (n = 21) and evaluation of only a single dose with short-term follow-up (up to 12 days). Long-term safety, durability of effect, and metabolic outcomes of repeated dosing were not assessed.
Cited by
- context Dr. Roger Unger published papers demonstrating that inhibiting glucagon excess in type 1 diabetes corrects hyperglycemia without requiring insulin administration.