Novel Preparations of Glucagon for the Prevention and Treatment of Hypoglycemia

Abstract

Purpose of review: New more stable formulations of glucagon have recently become available, and these provide an opportunity to expand the clinical roles of this hormone in the prevention and management of insulin-induced hypoglycemia. This is applicable in type 1 diabetes, hyperinsulinism, and alimentary hypoglycemia. The aim of this review is to describe these new formulations of glucagon and to provide an overview of current and future therapeutic opportunities that these may provide.

Recent findings: Four main categories of glucagon formulation have been studied: intranasal glucagon, biochaperone glucagon, dasiglucagon, and non-aqueous soluble glucagon. All four have demonstrated similar glycemic responses to standard glucagon formulations when administered during hypoglycemia. In addition, potential roles of these formulations in the management of congenital hyperinsulinism, alimentary hypoglycemia, and exercise-induced hypoglycemia in type 1 diabetes have been described. As our experience with newer glucagon preparations increases, the role of glucagon is likely to expand beyond the emergency use that this medication has been limited to in the past. The innovations described in this review likely represent early examples of a pending large repertoire of indications for stable glucagon.

Keywords: Alimentary; Diabetes; Formulation; Glucagon; Hyperinsulinism; Hypoglycemia.

Fig. 1

The islet cell and sympathoadrenal response to falling glucose concentrations in normal physiology

Fig. 2

Comparison of the glycemic effect of a dasiglucagon, b biochaperone glucagon, c NAS glucagon, and d intranasal glucagon when compared with standard formulations of glucagon (GlucaGen Hypokit). Mean glucose concentrations at each time-point are represented following administration at t = 0. a Includes 58 patients aged 18 to 50 years with T1D. Hypoglycemia (55 mg/dL ± 10%) was induced by insulin prior to glucagon administration. (adapted from Hovelman et al. [52], with permission from American Diabetes Association). b Includes 27 patients with T1D who received 1 mg of two different biochaperone glucagon formulations when plasma glucose was less than 60 mg/dL. Hypoglycemia was induced by intravenous insulin infusion. (adapted from Glezer et al. [53], with permission from American Diabetes Association). c Black points include 19 adult patients aged 18 to 65 years with T1D. Hypoglycemia was not routinely induced prior to glucagon administration in this study (adapted from Castle et al. [54], with permission from SAGE Publications). Gray points show 62 events of hypoglycemia in 16 adult patients with T1D. In this study, mini-dose (150 mcg) glucagon was used to treat mild hypoglycemia (50 to 69 mg/dL) detected by continuous glucose monitor. (adapted from Haymond et al. [55], with permission from Oxford University Press). d Includes 75 adults with T1D. Hypoglycemia (48 ± 8 mg/dL) was induced by insulin prior to glucagon administration. (adapted from Rickels et al. [56], with permission from American Diabetes Association)