What causes persistent hypoglycemia (low blood sugar)?

From the Guidelines

Blood sugar can keep dropping due to several factors, including medication effects, dietary patterns, and underlying health conditions, with the most significant risk factors being recent hypoglycemic episodes, intensive insulin therapy, and impaired hypoglycemia awareness, as identified in the 2025 standards of care in diabetes 1.

Causes of Hypoglycemia

• Medication effects: Insulin and other diabetes medications like sulfonylureas (glipizide, glyburide) can lower blood glucose too much, especially if doses are too high or meals are skipped 1.
• Dietary patterns: Skipping or delaying meals, consuming insufficient carbohydrates, or not eating after exercise can lead to hypoglycemia 1.
• Underlying health conditions: Medical conditions such as adrenal insufficiency, severe liver disease, or certain tumors can also cause recurrent low blood sugar 1.

Risk Factors for Hypoglycemia

• Recent hypoglycemic episodes: Individuals with recent level 2 or 3 hypoglycemia are at high risk for future episodes 1.
• Intensive insulin therapy: Rates of hypoglycemia are highest for individuals treated with intensive insulin therapy, including multiple daily injections of insulin, continuous subcutaneous insulin infusion, or automated insulin delivery systems 1.
• Impaired hypoglycemia awareness: Individuals with impaired hypoglycemia awareness are at high risk for severe hypoglycemia 1.

Management of Hypoglycemia

• Carry fast-acting carbohydrates: Individuals with diabetes should carry fast-acting carbohydrates like glucose tablets or juice to quickly treat hypoglycemic episodes 1.
• Follow a regular eating schedule: Eating regular meals can help prevent hypoglycemia 1.
• Monitor blood glucose levels: Regular monitoring of blood glucose levels can help identify hypoglycemic episodes early and prevent severe complications 1.
• Consult a healthcare provider: Individuals with frequent hypoglycemic episodes should consult their healthcare provider to adjust medication dosages or investigate underlying causes 1.

From the FDA Drug Label

Hypoglycemia:All sulfonylurea drugs are capable of producing severe hypoglycemia. Proper patient selection, dosage, and instructions are important to avoid hypoglycemic episodes Renal or hepatic insufficiency may cause elevated blood levels of glipizide and the latter may also diminish gluconeogenic capacity, both of which increase the risk of serious hypoglycemic reactions. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when alcohol is ingested, or when more than one glucose-lowering drug is used

The following factors can make your blood sugar keep dropping:

• Renal or hepatic insufficiency
• Deficient caloric intake
• Severe or prolonged exercise
• Alcohol ingestion
• Use of more than one glucose-lowering drug
• Beta-adrenergic blocking drugs 2
• Oral antidiabetic drugs, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAO inhibitors, propoxyphene, salicylates, somatostatin analog, and sulfonamide antibiotics can increase the blood-glucose-lowering effect of insulin and susceptibility to hypoglycemia 3

From the Research

Factors Contributing to Low Blood Sugar

• Certain therapies for diabetes, such as insulins and insulin secretagogues, including glinides and sulfonylureas, can increase the risk of hypoglycaemia 4, 5
• Intensified therapy to achieve glycaemic targets can also lead to a higher risk of severe hypoglycaemia 4
• Impairments in counterregulatory responses and hypoglycemia unawareness are main risk factors for severe hypoglycemia 5
• The use of sulfonylureas and insulin can increase the risk of severe hypoglycemia, especially in elderly people with type 2 diabetes 6

Patient-Specific Factors

• People with type 1 diabetes are at a higher risk of non-severe and severe hypoglycaemia 4
• Those with insulin-treated type 2 diabetes are also at risk of hypoglycaemia 4, 5
• Elderly subjects with type 2 diabetes and low HbA1c on sulfonylurea or insulin treatment are at a higher risk of hospitalization for severe hypoglycemia 6

Treatment-Related Factors

• The type of treatment used, such as sulfonylureas or insulin, can affect the risk of hypoglycaemia 7, 6
• The dose and frequency of treatment can also impact the risk of hypoglycaemia 4, 5
• New formulations of glucagon, such as nasal powder glucagon and liquid-stable glucagon, are available for the treatment of severe hypoglycaemia 8