Efficacy and safety of the glucagon receptor antagonist volagidemab in type-1 diabetes: A systematic review and meta-analysis

The glucagon receptor antagonist (GRA) volagidemab is the first-in-class fully human monoclonal antibody that inhibits glucagon receptor. GRA can improve glycemia by reducing endogenous glucose production and reduce risks of diabetic ketoacidosis by suppressing ketogenesis. This systematic review and meta-analysis analyzed the efficacy and safety of volagidemab in type-1 diabetes (T1D). Electronic databases were searched for randomized controlled trials (RCTs) involving T1D patients receiving volagidemab. The primary outcome was to evaluate changes in total daily dose (TDD) of insulin. The secondary outcomes were to evaluate changes in measures of glycemia, hypoglycemia, and adverse events. Data from 3 RCTs (98 patients) were analyzed. Volagidemab (70 mg/week) was associated with a significant reduction in TDD of insulin requirement (mean difference [MD]: -8.45 units/day (95% confidence interval [CI]: [-12.09, -4.81]); I² = 83%; p < 0.01) and average blood glucose (MD: -21.42 mg/dL (95% CI: [-37.10, -5.74]); I² = 88%; p < 0.01), compared to placebo. Volagidemab use was associated with a significant increase in time in range (blood glucose: 70-180 mg/dL) (MD: 10.93% (95% CI: [6.69, 15.17]); I² = 55%; p < 0.01) and significant reduction in time above range (blood glucose >180 mg/dL) (MD: -11.93% (95% CI: [-14.71, -9.15]); I² = 6%; p < 0.01) without any impact on time below range (blood glucose <70 mg/dL) (MD: 0.14% (95% CI: [-0.56, 0.84]); I² = 0%; p = 0.70), compared to placebo. Occurrence of treatment-emergent adverse events (odds ratio [OR]: 0.96 (95% CI: [0.36, 2.56]); I² = 8%; p = 0.94) and hypoglycemia (OR: 0.56 (95% CI: [0.11, 2.89]); I² = 0%; p = 0.49) were similar among volagidemab users as compared to placebo. Short-term volagidemab use was associated with significant reduction in insulin requirement along with improvement in glycemia.