Drug-Induced Hypoglycemia

Chapter: Drug-Induced Hypoglycemia
McMaster Section Editor(s): Victor M. Montori, Juan P. Brito
Section Editor(s) in Interna Szczeklika: Barbara Jarząb, Ewa Płaczkiewicz-Jankowska
McMaster Author(s): René Rodríguez-Gutiérrez, Analy Velez-Viveros, Armando Quintanilla-Siller, Fernando J. Lavalle-Gonzalez
Author(s) in Interna Szczeklika: Jacek Sieradzki, Ewa Płaczkiewicz-Jankowska
Additional Information

Definition and EtiologyTop

Drug-induced hypoglycemia is a plasma glucose level <3.9 mmol/L (70 mg/dL) regardless of symptoms of hypoglycemia. Symptoms may first appear in patients with lower blood glucose levels (eg, in those with long-standing, well-controlled type 1 diabetes [hypoglycemia unawareness]) or in patients with blood glucose levels still >5.6 mmol/L (100 mg/dL) in whom the level has rapidly decreased.


1) An excessively high dose of antidiabetic drugs (insulin or sulfonylureas) in relation to food intake and physical activity levels.

2) Impaired physiological mechanisms preventing hypoglycemia recognition, such as autonomic failure or as in patients with renal impairment.

3) Decreased endogenous glucose production (eg, after alcohol intake).

4) Increased insulin sensitivity (eg, after a decrease in body weight, as a delayed effect of exercise, or due to improved diabetes control).

The risk of hypoglycemia is increased in patients in whom intensive insulin therapy is used to achieve the normalization of blood glucose levels and glycated hemoglobin levels (HbA1c) <7.0%. Episodes of hypoglycemia are less frequent in patients with type 2 diabetes, even in those receiving intensive insulin therapy.


1. Documented symptomatic hypoglycemia: An event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration ≤3.9 mmol/L (70 mg/dL).

2. Asymptomatic hypoglycemia: An event without typical symptoms of hypoglycemia and a measured plasma glucose concentration ≤3.9 mmol/L (70 mg/dL).

3. Mild episodes of hypoglycemia: The patient is capable of self-managing the episode by consuming sweetened beverages and foods.

4. Severe hypoglycemia: Altered mental status that requires assistance of a third party to actively administer carbohydrates, glucagon, or take other corrective actions. This usually requires an active follow-up even with hospital admission.

Clinical Features and DiagnosisTop

1. Clinical features:

1) General signs and symptoms: Dizziness, blurred vision, pallor, nausea, and light-headedness.

2) Perspiration, palpitations, tremor, hunger, anxiety, and profuse perspiration; these are caused by sympathetic stimulation (starting in patients with blood glucose levels of approximately 3.3 mmol/L [60 mg/dL]).

3) Confusion, somnolence, dysarthria, abnormal coordination, atypical behavior, visual disturbances, migrant paresthesia, and coma; these are manifestations of neuroglycopenia (glucose deficit in the central nervous system), which may develop in patients with blood glucose levels <2.8 mmol/L (50 mg/dL).

2. In some patients, the symptoms and signs of hypoglycemia may be absent despite very low glucose levels. This is referred to as hypoglycemia unawareness. Causes:

1) Autonomous nervous system dysfunction in patients with long-standing diabetes causes a loss of warning signs related to adrenergic stimulation. This leads to features of neuroglycopenia appearing without warning symptoms.

2) Dysregulation of the mechanisms that prevent hypoglycemia, which may occur after previous episodes of severe hypoglycemia and may require temporary adoption of less stringent criteria of glycemic control.

Differential Diagnosis

1. Hypoglycemia caused by other factors: Insulinoma and other conditions (see Other Well-Differentiated Gastrointestinal and Pancreatic Neuroendocrine Neoplasms).

2. Loss of consciousness caused by other conditions: Coma in the course of diabetes (see Diabetic Ketoacidosis), syncope, epilepsy.


Acute Treatment

1. Mild hypoglycemia: Intake of fast-acting carbohydrates (eg, 10-15 g of glucose in tablets or gel) or foods/fluids (fruit juice, hard bar candy); this may be repeated when necessary. Subsequently, the patient should consume complex (long-lasting) carbohydrates to prevent recurrent hypoglycemia (eg, bread, potatoes, cereal, nuts, peanuts). All patients, and particularly patients using insulin pumps or treated with insulin analogues as part of an intensive insulin therapy regimen, should consume 15 g of glucose and measure their blood glucose level after 15 minutes (the 15/15 rule); this should be repeated in case of persistent hypoglycemia.

2. Severe hypoglycemia: In patients with altered mental status or those unable to swallow, administer 20% glucose (dextrose) IV (0.2 g glucose/kg, even up to 80-100 mL of the solution; in Canada up to 50 mL of a 50% glucose solution is used), followed by an intravenous infusion of a 10% glucose solution until the mental status improves and the patient is able to take oral carbohydrates. In the case of severe hypoglycemia in patients with type 1 diabetes in whom it is difficult to establish intravenous access, administer glucagon 0.5 to 1 mg IM or subcutaneously; if there is no improvement, repeat after 10 minutes. Use glucagon with caution in patients with type 2 diabetes. Do not use glucagon in patients with hypoglycemia caused by sulfonylureas (as it may paradoxically stimulate the secretion of endogenous insulin and worsen the hypoglycemia episode). Glucagon is also contraindicated in patients who have recently consumed alcohol.

Further Management

1. Assess the risk of recurrence: Hypoglycemia caused by long-acting sulfonylureas, intermediate-acting insulins, or long-acting insulin analogues may recur even after 16 to 20 hours (particularly in patients with impaired renal function). When using premixed insulins, note that they have 2 peaks of action (one after 2-4 hours and another after 8-12 hours).

2. Assess the frequency and time of occurrence of hypoglycemia and adjust the treatment of diabetes appropriately:

1) Hypoglycemia occurring at a specified time: Adjust nutrition management and insulin doses.

2) Hypoglycemia occurring at irregular intervals: Identify and address the causes, including irregular meals, inappropriate insulin injection techniques, variable intensity of exercise, alcohol use, gastric motility disorders, and variable rates of carbohydrate absorption from the gastrointestinal tract.

3) Hypoglycemia unawareness: Adjust treatment to reduce the incidence of episodes of hypoglycemia. Educate patients and their caregivers/family members how to recognize the less typical prodromal symptoms of hypoglycemia. Consider the use of a continuous glucose monitoring system. Consider the risk of hypoglycemia unawareness at work or when driving.

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