What are the causes of hypoglycemia (low blood sugar)?

From the Guidelines

Hypoglycemia is primarily caused by medications used to treat diabetes, particularly insulin, and errors in insulin dosing, missed doses, and/or administration errors, as well as kidney failure, which is an important risk factor for hypoglycemia in the hospital. The most common causes of hypoglycemia include:

• Medications used to treat diabetes, such as insulin and sulfonylureas like glipizide and glyburide, which can lower blood glucose too much, especially if doses are too high, meals are missed, or physical activity increases unexpectedly 1
• Errors in insulin dosing, missed doses, and/or administration errors, including incorrect insulin type and incorrect timing of dose, which occur relatively frequently 1
• Kidney failure, which is an important risk factor for hypoglycemia in the hospital, possibly as a result of decreased insulin clearance 1
• Other causes, such as excessive alcohol consumption without food, severe liver or kidney disease, certain hormonal deficiencies, and rare tumors like insulinomas, can also trigger hypoglycemia 1 The symptoms of hypoglycemia typically include shakiness, sweating, confusion, irritability, and in severe cases, seizures or loss of consciousness. Treatment involves consuming 15-20 grams of fast-acting carbohydrates like glucose tablets or juice, followed by a more substantial snack containing protein and complex carbohydrates to maintain blood glucose levels. People at risk should carry glucose tablets and monitor blood sugar regularly, especially when changing medication regimens or activity levels. According to the most recent study, adopting a hypoglycemia management surveillance protocol and implementing "bundled" preventive therapies, including proactive surveillance of glycemic outliers and an interdisciplinary data-driven approach to glycemic management, can reduce hypoglycemic episodes in the hospital by 56-80% 1.

From the FDA Drug Label

Metformin hydrochloride tablets rarely cause hypoglycemia (low blood sugar) by themselves. However, hypoglycemia can happen if you do not eat enough, if you drink alcohol, or if you take other medicines to lower blood sugar.

Insulin and insulin secretagogues (e.g., sulfonylurea) are known to cause hypoglycemia. Metformin hydrochloride tablets may increase the risk of hypoglycemia when combined with insulin and/or an insulin secretagogue.

The causes of hypoglycemia include:

• Not eating enough
• Drinking alcohol
• Taking other medicines to lower blood sugar, such as insulin or insulin secretagogues
• Combining metformin with insulin and/or an insulin secretagogue 2, 2 Note that hypoglycemia can also be caused by other factors not directly related to metformin or insulin, such as skipped meals or inadequate food intake, as well as intercurrent conditions like illness, stress, or emotional disturbances 3

From the Research

Causes of Hypoglycemia

• Hypoglycemia is a common condition in patients with type 1 diabetes and type 2 diabetes, and it constitutes a major limiting factor in achieving glycaemic control among people with diabetes 4.
• The use of insulin and/or sulphonylureas increases the risk of hypoglycaemia 4, 5.
• Certain drugs, including NSAIDs, analgesics, antibacterials, antimalarials, antiarrhythmics, antidepressants, and other miscellaneous agents, can induce hypoglycaemia by stimulating insulin release, reducing insulin clearance, or interfering with glucose metabolism 6.
• Sulfonylureas and meglitinides can induce hypoglycemia, which may be associated with falls/fractures and cardiovascular events, especially in older patients 7.
• Other factors that can contribute to hypoglycemia include poor glycaemic control, impaired hypoglycaemia awareness, frequent nocturnal hypoglycaemia, and a history of severe hypoglycaemia 4, 5.

Drug-Induced Hypoglycemia

• Drugs are the most frequent cause of hypoglycaemia in adults, and they can induce hypoglycaemia through various mechanisms, including stimulating insulin release, reducing insulin clearance, or interfering with glucose metabolism 6.
• Certain medications, such as sulfonylureas and meglitinides, have a higher risk of inducing hypoglycemia compared to others, such as gliptins and gliflozins 7.
• The risk of drug-induced hypoglycemia can be increased in certain populations, such as older patients with comorbidities, including renal impairment, vascular disease, heart failure, risk of dehydration, osteoporosis, and cognitive dysfunction 7.

Prevention and Management

• Education and regular review are essential between people with diabetes and their caregivers and healthcare professionals about symptoms, prevention, and treatment of hypoglycemia 4, 5.
• A tailored approach, using clinical and pathophysiologic disease stratification, can help individualize glycaemic goals and promote new therapies to improve the quality of life of patients 4.
• Continuous glucose monitoring (CGM) should be considered for all individuals with increased risk for hypoglycaemia, impaired hypoglycaemia awareness, frequent nocturnal hypoglycaemia, and with a history of severe hypoglycaemia 4.
• Optimizing insulin doses and carbohydrate intake, in addition to a short warm-up before or after physical activity sessions, may help avoid hypoglycaemia 4.