What factors can lower blood glucose levels?

Several physiological, pharmacological, and lifestyle-related factors can lower blood glucose levels. Endogenously, insulin—secreted by pancreatic beta cells in response to elevated blood glucose—is the primary hormone responsible for facilitating glucose uptake into skeletal muscle and adipose tissue, suppressing hepatic glucose production, and promoting glycogen synthesis. Counter-regulatory hormones such as glucagon, cortisol, epinephrine, and growth hormone normally oppose insulin’s action; thus, deficiencies or imbalances in these (e.g., adrenal insufficiency or hypopituitarism) may predispose individuals to hypoglycemia.

Pharmacologically, insulin therapy and insulin secretagogues—including sulfonylureas (e.g., glipizide, glyburide) and meglitinides (e.g., repaglinide)—are common causes of iatrogenic hypoglycemia, particularly in people with diabetes. Other medications associated with reduced blood glucose include metformin (rarely, especially when combined with other agents or in renal impairment), GLP-1 receptor agonists (e.g., semaglutide, liraglutide), SGLT2 inhibitors (e.g., empagliflozin), and certain antibiotics (e.g., sulfonamides, pentamidine). Alcohol consumption—especially on an empty stomach—can inhibit gluconeogenesis in the liver and precipitate hypoglycemia, particularly in fasting or malnourished individuals.

Lifestyle and clinical factors also play key roles: prolonged fasting or inadequate caloric intake, excessive or unplanned physical activity (which increases glucose utilization and insulin sensitivity), rapid weight loss, and critical illness (e.g., sepsis, liver failure, or advanced heart failure) can all impair glucose homeostasis. Rare but important causes include insulinoma, non-islet cell tumor–induced hypoglycemia (NICTH), autoimmune hypoglycemia (e.g., insulin antibodies), and congenital disorders of carbohydrate metabolism (e.g., glycogen storage diseases, hereditary fructose intolerance).

Clinicians must consider the full clinical context—including timing relative to meals and activity, medication history, comorbidities, and laboratory findings (e.g., C-peptide, insulin, proinsulin, beta-hydroxybutyrate, cortisol)—to accurately diagnose the underlying cause of hypoglycemia and guide appropriate management.