Hypoglycemia, defined as a plasma glucose concentration <70 mg/dL, represents a major and potentially very dangerous side effect of glucose-lowering therapies in patients with diabetes, and it challenges the patient’s ability to achieve and maintain optimal glycemic control (1–3). Statistically, the incidence of mild hypoglycemia in patients with type 1 diabetes is ~30 episodes/patient/year, whereas the incidence of severe hypoglycemia (i.e., requiring third-party assistance) may be as high as 3.2 episodes/patient/year (4). Furthermore, an estimated 2–4% of deaths of people with type 1 diabetes have been attributed to hypoglycemia. On the other hand, patients with type 2 diabetes experience hypoglycemia less frequently, with an incidence of mild and severe hypoglycemic episodes of 2–10/patient/year and 0.1–0.7/patient/year, respectively (4). The occurrence of hypoglycemia, both in experimental and human settings even without diabetes or related metabolic changes, provokes substantial increase in counterregulatory hormonal secretion and affects the cardiovascular system and the brain, in turn affecting cognition, mood, and the level of consciousness. The secretion of counterregulatory hormones—of which glucagon and epinephrine are the most potent but also including norepinephrine, vasopressin, growth hormone, and cortisol—follows suppression of endogenous insulin secretion (5). In addition, a specific response that occurs within the brain includes the activation of the central sympathetic nervous system, which promotes autonomic symptoms such as sweating, tremor, a pounding heart, hunger, and anxiety (6). Severe hypoglycemia is associated with significant morbidity such as cognitive impairment and can cause major neurological disability, including difficulty concentrating, drowsiness, and poor coordination. When blood glucose falls below 2.8 mmol/L, the majority of cognitive modalities are impaired. It is essential for a patient to be aware of these neuroglycopenic symptoms because they warn him/her that prompt action is required to treat the hypoglycemia and restore blood glucose to normal. In rare cases, prolonged severe …