What is the major side effect associated with long-term use of glucocorticoids?

The major side effect associated with long-term use of glucocorticoids is hyperglycemia. Glucocorticoids, such as prednisone, can increase insulin resistance and mobilize glucose from the liver, leading to elevated blood sugar levels. This hyperglycemic effect is particularly significant because it can lead to the development of corticosteroid-induced diabetes, especially in patients who already have risk factors for diabetes.

Chronic exposure to these medications also affects carbohydrate metabolism and can influence the body's ability to regulate glucose effectively. This makes monitoring blood glucose levels critical in patients receiving long-term glucocorticoid therapy.

Other potential side effects of glucocorticoids include fluid retention and hypertension, but hyperglycemia is a direct and prominent concern linked to their mechanism of action. Weight loss is typically not associated with glucocorticoid use; in fact, weight gain is more common. Hypokalemia, while it can occur, is not as frequent as hyperglycemia and is generally seen with specific glucocorticoid use or in conjunction with other medications. Therefore, hyperglycemia is recognized as the major side effect requiring attention with long-term glucocorticoid therapy.