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Effect of a glucagon receptor antibody (REMD-477) in type 1 diabetes: A randomized controlled trial
Jeremy Pettus1, Dominic Reeds2, Tricia S Cavaiola1
1Department of Medicine, University of California San Diego, San Diego, California.
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.
Insights
REMD-477, a glucagon receptor antagonist, significantly reduced insulin needs and improved glycemic control in type 1 diabetes patients. This study found it safe and effective for managing blood sugar levels.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Clinical Trials
Background:
- Type 1 diabetes (T1D) management requires careful insulin therapy to maintain glycemic control.
- Glucagon plays a key role in hyperglycemia in T1D.
- Targeting the glucagon receptor is a potential therapeutic strategy for T1D.
Purpose of the Study:
- To evaluate the efficacy and safety of REMD-477, a novel glucagon receptor antagonist.
- To assess the impact of REMD-477 on glycemic control and insulin requirements in T1D patients.
Main Methods:
- Randomized controlled trial (NCT02715193) involving 21 T1D patients.
- Single 70-mg dose of REMD-477 or placebo administered.
- Evaluation of insulin use and continuous glucose monitoring (CGM) data.
Main Results:
- REMD-477 reduced inpatient insulin use by 26% compared to placebo (P = .02).
- CGM showed lower average daily glucose (-27 mg/dL), increased time-in-range (~25%), and decreased time-in-hyperglycemia (~40%) with REMD-477.
- No serious adverse events were reported; no difference in hypoglycemia was observed.
Conclusions:
- Glucagon receptor antagonism with REMD-477 effectively improves glycemic control in T1D.
- REMD-477 reduces insulin requirements in T1D patients.
- REMD-477 demonstrates a favorable safety profile in this T1D cohort.
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