Systematic Literature Review and Indirect Treatment Comparison of Three Ready-to-Use Glucagon Treatments for Severe Hypoglycemia

Marga Giménez; Kamlesh Khunti; Munehide Matsuhisa; Suresh Chenji; Kristen Syring; Yu Yan

doi:10.1007/s13300-023-01466-6

Systematic Literature Review and Indirect Treatment Comparison of Three Ready-to-Use Glucagon Treatments for Severe Hypoglycemia

Diabetes Ther. 2023 Nov;14(11):1757-1769. doi: 10.1007/s13300-023-01466-6. Epub 2023 Sep 14.

Authors

Marga Giménez¹, Kamlesh Khunti², Munehide Matsuhisa³, Suresh Chenji⁴, Kristen Syring⁴, Yu Yan⁵

Affiliations

¹ Hospital Clínic, Barcelona, Spain.
² University of Leicester, Leicester, UK.
³ Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
⁴ Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
⁵ Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. yan_yuer@lilly.com.

Abstract

Introduction: Ready-to-use glucagon represents a significant advancement in the management of severe hypoglycemia for people with diabetes and their caregivers. This indirect treatment comparison (ITC) evaluated the efficacy and safety differences among the three ready-to-use glucagon treatments, Baqsimi^® (nasal glucagon), Gvoke^® (glucagon injection) and Zegalogue^® (dasiglucagon injection), in adults and children with type 1 diabetes (T1D) or type 2 diabetes (T2D).

Methods: A systematic literature review was conducted to identify randomized clinical trials assessing the efficacy and safety of Baqsimi, Gvoke or Zegalogue versus reconstituted, injectable glucagon (IG) in reversing insulin-induced hypoglycemia. Bayesian fixed-effect network meta-analysis was used to perform the ITC. Study endpoints included proportion of participants achieving treatment success, maximum blood glucose achieved, time to achieve treatment success and maximum blood glucose and treatment-emergent adverse events (TEAE).

Results: Ten clinical trials were included in the ITC (four for Baqsimi, three for Gvoke, and three for Zegalogue). All three treatments achieved high proportions of treatment success (> 98%). In adults, the efficacy results from combined T1D and T2D analysis were consistent with the T1D analysis, except statistically significantly faster in achieving treatment success for Baqsimi vs Gvoke in the combined analysis (13.96 vs 14.66 min). The mean maximum blood glucose values were also statistically significantly lower for Baqsimi (168 mg/dl) vs Gvoke (220 mg/dl) and Zegalogue (190 mg/dl). There was a trend towards a lower number of adults experiencing ≥ 1 TEAE with Baqsimi compared to Gvoke or Zegalogue, but no statistical significance was reached.

Conclusion: Baqsimi, Gvoke and Zegalogue had comparable high proportions of treatment success in reversing insulin-induced hypoglycemia. Baqsimi achieved a lower mean maximum blood glucose value, which may have implications for the re-establishment of euglycemia. These findings may help support patients, caregivers and health care providers in their decision-making process when discussing various ready-to-use glucagon treatment options.

Keywords: Baqsimi®; Gvoke®; Hypoglycemia; Indirect treatment comparison; Ready-to-use glucagon; Type 1 diabetes; Type 2 diabetes; Zegalogue®.

Publication types

Review