Managing Severe Hypoglycaemia in Patients with Diabetes: Current Challenges and Emerging Therapies

Hypoglycaemia is common in patients with diabetes mellitus and is a limiting factor for achieving adequate glycaemic control. In the vast majority of cases, hypoglycaemia develops due to the imbalance between food intake and insulin injections. As recurrent hypoglycaemia leads to significant morbidity and mortality, the recognition and immediate treatment of hypoglycaemia in diabetic patients is thus important. In the last 20 years, the introduction of improved insulin analogues, insulin pump therapy, continuous glucose monitoring (CGM), and sensor-augmented pump therapy have all made significant improvements in helping to reduce and prevent hypoglycaemia. In terms of treatment, the American Diabetes Association recommends oral glucose as the first-line treatment option for all conscious patients with hypoglycaemia. The second line of treatment (or first line in unconscious patients) is the use of glucagon. Novel formulations of glucagon include the nasal form, the Gvoke HypoPen which is a ready-to-deliver auto-injector packaged formulation and finally a glucagon analogue, Dasiglucagon. The Dasiglucagon formulation has recently been approved for the treatment of severe hypoglycaemia. It is a ready-to-use, similar to endogenous glucagon and its potency is also the same as native glucagon. It does not require reconstitution before injection and therefore ensures better compliance. Thus, significant improvements including development of newer insulin analogues, insulin pump therapy, continuous glucose monitoring (CGM), sensor-augmented pump therapy and novel formulations of glucagon have all contributed to reducing and preventing hypoglycaemia in diabetic individuals. However, considerable challenges remain as not all patients have access to diabetes technologies and to the newer glucagon formulations to help reduce and prevent hypoglycaemia.