Glucagon Therapy: A Comparison of Current and Novel Treatments.

Abstract

Hypoglycemia has been a barrier to A1C attainment in people with diabetes (1). It is well known that a glucocentric approach with intensive control reduces microvascular complications, but at what cost? Worse clinical outcomes, increased risk of severe hypoglycemia, and heavier treatment burden can result from aggressive efforts to lower A1C (2). People with diabetes also tend to experience more stress as a result of fear of hypoglycemia, higher costs of care, and increased prevalence of polypharmacy—especially for those with type 2 diabetes of longer duration. New medication classes (e.g., sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists) are providing impetus for replacing the glucocentric treatment paradigm with an individualized multifactorial approach (2). Traditional glucagon kits have long been available for the ambulatory treatment of patients with hypoglycemia. However, these kits have disadvantages. Their complicated multistep injection procedure can be difficult to perform. Additionally, the use of glucagon must be taught to the family members, friends, or caregivers because it is administered by someone else when a person with diabetes is unconscious or otherwise incapacitated by severe hypoglycemia (3). For these reasons, glucagon is undertaught and underutilized (3). Two new glucagon formulations offer potentially easier delivery. The purpose of this article is to review all available glucagon formulations, discussing the associated literature and possible new directions for the treatment of hypoglycemia. The American Diabetes Association has adopted a three-level classification of hypoglycemia. Level 1 is a glucose concentration <70 and ≥54 mg/dL; level 2 is glucose <54 mg/dL; and level 3 is defined as a severe event characterized by altered mental and/or physical status requiring assistance (1). Symptoms include dizziness, shakiness, sweating, intense hunger or thirst, irritability, and anxiety. Although many patients experience symptoms, possible impaired counterregulatory responses necessitate adherence to glucose concentrations as clinical indicators. …