Why do corticosteroids (corticosteroid) increase blood serum glucose levels, leading to hyperglycemia?

From the Guidelines

Corticosteroids increase blood serum glucose through multiple mechanisms that interfere with normal glucose metabolism, including promoting gluconeogenesis, inducing insulin resistance, and impairing insulin secretion, as evident in a study published in 2025 1. These medications, such as prednisone, dexamethasone, and hydrocortisone, have dose-dependent effects, with longer-acting corticosteroids like dexamethasone causing more pronounced hyperglycemia compared to shorter-acting ones like hydrocortisone.

Key Mechanisms

• Promoting gluconeogenesis in the liver, causing increased production of glucose from non-carbohydrate sources
• Reducing glucose uptake and utilization in peripheral tissues by inducing insulin resistance in muscle and fat cells
• Stimulating the breakdown of proteins and lipids, providing more substrates for glucose production
• Directly impairing insulin secretion from pancreatic beta cells, further contributing to hyperglycemia According to a recent study published in 2025, the typical glycemic pattern for individuals treated with daily prednisone or prednisolone is characterized by normal or mild fasting hyperglycemia, with trends of increasing hyperglycemia during the afternoon, and peaking in the evening 1.

Clinical Implications

• Patients on corticosteroid therapy, especially those with risk factors for diabetes, should monitor their blood glucose levels regularly
• The hyperglycemic effect is usually reversible upon discontinuation of the medication, though it may persist for days to weeks depending on the specific corticosteroid used and its duration of action
• Appropriate insulin treatments should be determined based on the glucocorticoid type and duration of action, as well as the individual's glucose levels and response to treatment, as recommended in a study published in 2023 1.

From the FDA Drug Label

Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required. The FDA drug label states that corticosteroids may increase blood glucose concentrations.

• The exact mechanism is not specified in the label, but it is implied that this increase in blood glucose is a direct effect of corticosteroid use.
• As a result, dosage adjustments of antidiabetic agents may be required to manage blood glucose levels in patients taking corticosteroids 2, 2.

From the Research

Corticosteroids and Blood Serum Glucose

• Corticosteroids have been shown to increase blood serum glucose levels in various studies 3, 4, 5, 6.
• The mechanism of this increase is not fully understood, but it is thought to be related to the glucocorticoid effects of corticosteroids, which can cause insulin resistance and increase glucose production in the liver 5.
• Different types of corticosteroids may have varying effects on blood glucose levels, with some studies suggesting that dexamethasone and methylprednisolone may be more likely to cause hyperglycemia than hydrocortisone and prednisolone 3.
• The increase in blood glucose levels associated with corticosteroid use can be significant, with one study finding a mean difference of 16.6 mg/dL (0.92 mmol/L) between dexamethasone and hydrocortisone 3.
• The effects of corticosteroids on blood glucose levels can be particularly significant in patients with diabetes, who may experience worsening glucose control or new-onset hyperglycemia 4, 5.

Patterns of Hyperglycemia

• The pattern of hyperglycemia associated with corticosteroid use can vary, with some studies suggesting that blood glucose levels may be higher at certain times of the day 3.
• However, other studies have found no significant differences in the patterns of hyperglycemia at different times of the day 3, 4.
• The duration of corticosteroid treatment can also impact the degree of hyperglycemia, with longer treatment durations potentially leading to more significant increases in blood glucose levels 4, 6.

Clinical Implications

• The increase in blood glucose levels associated with corticosteroid use has significant clinical implications, particularly in patients with diabetes or those at risk of developing diabetes 5, 6.
• Clinicians should be aware of the potential for corticosteroids to cause hyperglycemia and monitor patients closely for signs of worsening glucose control 3, 5.
• Strategies for managing steroid-induced hyperglycemia, such as adjusting medication regimens or implementing insulin therapy, may be necessary to mitigate the risks associated with corticosteroid use 5, 6.