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INDIRECT TREATMENT COMPARISON OF READY-TO-USE GLUCAGON RESCUE TREATMENTS FOR SEVERE HYPOGLYCEMIA: NASAL GLUCAGON VERSUS LIQUID STABLE GLUCAGON
Abstract
Background and Aims
An indirect treatment comparison (ITC) evaluated the efficacy and safety differences between 2 ready-to-use severe hypoglycemia rescue treatments, nasal glucagon (NG, Eli Lilly and Company) and liquid stable glucagon rescue pen (GRP, Xeris Pharmaceuticals), in adults with type 1 or type 2 diabetes.
Methods
Systematic literature reviews identified 3 randomized clinical trials assessing the efficacy and safety of NG versus reconstituted injectable glucagon (IG), and 3 trials of GRP versus IG. No head-to-head trials of NG versus GRP were identified. The Bayesian fixed-effect network meta-analysis was used to perform the ITC. Endpoints included the proportion of participants achieving treatment success (defined as increase in blood glucose to ≥70mg/dL or an increase of ≥20mg/dL from nadir blood glucose within 30mins), maximum blood glucose, and treatment-emergent adverse events (TEAE). Participants with a nadir blood glucose value of ≤54mg/dL were analyzed.
Results
A similar proportion of GRP (98.9%[279/282]) and NG participants (99.4%[155/156]) achieved treatment success (Wald method p=0.63). The mean max blood glucose values were 220mg/dL for GRP and 168mg/dL for NG, with a significant treatment difference between GRP and NG, while adjusting IG as a comparator (17.32mg/dL, 95% credible interval: [3.94, 30.97]). Proportions of participants experiencing ≥1 TEAE were 48.8% for GRP and 38.5% for NG (odds ratio: 1.31[0.67, 2.31]). Subgroup analyses showed consistent results.
Conclusions
NG and GRP had comparable efficacy in reversing insulin-induced hypoglycemia in adults with diabetes. NG had a mean max blood glucose below 180mg/dL, which may have implications on the re-establishment of euglycemia after severe hypoglycemia rescue.