What causes hypoglycemia (low blood sugar)?

From the Guidelines

Hypoglycemia is primarily caused by insulin and other glucose-lowering medications, with errors in dosing, administration, and management being common preventable sources of iatrogenic hypoglycemia. According to a recent study published in 2024 1, insulin is one of the most common medications causing adverse events in hospitalized individuals, with errors in insulin dosing, missed doses, and administration errors occurring relatively frequently.

Common Causes of Hypoglycemia

• Insulin excess due to overdosing, timing mismatches with meals, or increased insulin sensitivity
• Other glucose-lowering medications, such as sulfonylureas
• Kidney failure, which can decrease insulin clearance 1
• Sudden reduction of corticosteroid dose, reduced oral intake, emesis, or unexpected interruption of enteral or parenteral feedings 1
• Inappropriate timing of short- or rapid-acting insulin doses in relation to meals 1

Prevention and Management

• Proactive surveillance of glycemic outliers and an interdisciplinary data-driven approach to glycemic management can reduce hypoglycemic episodes by 56-80% 1
• The use of continuous glucose monitoring (CGM) as an early warning system to alert of impending hypoglycemia, offering an opportunity to mitigate it before it happens 1
• Evaluation of all hypoglycemic episodes for a root cause and aggregation and review of episodes to address systemic issues, as recommended by The Joint Commission 1

From the FDA Drug Label

Hypoglycemia in Patients with Insulinoma: In patients with insulinoma, administration may produce an initial increase in blood glucose; however, Glucagon for Injection may stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. Hypoglycemia in Patients with Glucagonoma when Used as a Diagnostic Aid: Glucagon administered to patients with glucagonoma may cause secondary hypoglycemia.

Hypoglycemia causes related to glucagon use include:

• Insulinoma: Glucagon may stimulate exaggerated insulin release, causing hypoglycemia.
• Glucagonoma: Glucagon administration may cause secondary hypoglycemia. 2

From the Research

Hypoglycemia Causes

Hypoglycemia is a common complication in patients with diabetes, and several factors contribute to its causes. Some of the key causes of hypoglycemia include:

• Impairments in counterregulatory responses and hypoglycemia unawareness, which constitute the main risk factors for severe hypoglycemia 3
• Therapies for diabetes that increase the risk of hypoglycaemia, such as insulins and insulin secretagogues, including glinides and sulfonylureas 4
• Increased hypoglycaemia risk observed with the use of insulin and/or sulphonylureas 5
• Use of beta-blockers, which can attenuate some components of the autonomic response to hypoglycemia and increase the risk of hypoglycemia 6
• Use of angiotensin-converting enzyme (ACE) inhibitors, which may increase insulin sensitivity and predispose users to hypoglycemia 6

Risk Factors

Certain individuals are at a higher risk of developing hypoglycemia, including:

• Patients with type 1 diabetes, who have higher rates of non-severe and severe hypoglycaemia 4
• Patients with insulin-treated type 2 diabetes, who are also at risk of hypoglycaemia 4
• Vulnerable patients with type 2 diabetes at dual risk of severe hypoglycaemia and cardiovascular outcomes, who may show features of "frailty" 5
• Patients with impaired awareness of hypoglycaemia, who may benefit from real-time continuous glucose monitoring (CGM) 5

Prevention and Management

To prevent and manage hypoglycemia, several strategies can be employed, including:

• Patient education regarding risk factors, warning signs, and treatment of hypoglycemia at an early stage 3
• Setting personalized goals for glycemic control 3
• Use of continuous glucose monitoring (CGM) for individuals with increased risk for hypoglycaemia, impaired hypoglycaemia awareness, frequent nocturnal hypoglycaemia, and with history of severe hypoglycaemia 5
• Optimizing insulin doses and carbohydrate intake, and a short warm-up before or after physical activity sessions to avoid hypoglycaemia 5