Is prednisolone or a statin (HMG-CoA reductase inhibitor) more likely to cause hyperglycemia (diabetes)?

From the Guidelines

Prednisolone is more likely to cause hyperglycemia (diabetes) than statins, with a significantly higher risk of inducing hyperglycemia in 56-86% of individuals, regardless of preexisting diabetes. This is because prednisolone, a corticosteroid, promotes insulin resistance, increases glucose production in the liver, and can directly impair pancreatic beta cell function, as noted in the 2025 standards of care in diabetes 1. The risk is dose-dependent, with higher doses and longer treatment durations substantially increasing the likelihood of developing steroid-induced diabetes. In contrast, statins can also increase diabetes risk, but to a much lesser extent.

Key Considerations

• The prevalence of glucocorticoid therapy in hospitalized patients can approach 10-15%, and these medications can induce hyperglycemia in patients with and without antecedent diabetes 1.
• Daily-ingested intermediate-acting glucocorticoids such as prednisone reach peak plasma levels in 4–6 h but have pharmacologic actions that last throughout the day, leading to disproportionate hyperglycemia during the day 1.
• Patients on morning steroid regimens have disproportionate hyperglycemia during the day, but they frequently reach normal blood glucose levels overnight regardless of treatment 1.
• For higher doses of glucocorticoids, increasing doses of prandial and correctional insulin, sometimes in extraordinary amounts, are often needed in addition to basal insulin 1.

Monitoring and Management

• If you're taking prednisolone, especially at higher doses or for extended periods, your healthcare provider should monitor your blood glucose levels regularly.
• Patients with existing risk factors for diabetes (family history, obesity, history of gestational diabetes) should be particularly vigilant when taking either medication, but especially prednisolone.
• Adjustments based on anticipated changes in glucocorticoid dosing and point-of-care glucose test results are critical to manage hyperglycemia effectively 1.

From the FDA Drug Label

1. 4 Increases in HbA1c and Fasting Serum Glucose Levels Increases in HbA1c and fasting serum glucose levels have been reported with statins, including atorvastatin.

• Hyperglycemia is a potential side effect of statins, including atorvastatin.
• The provided drug label does not mention prednisolone, therefore, a direct comparison between prednisolone and atorvastatin regarding the risk of hyperglycemia cannot be made based on this information.
• However, it is well-known that corticosteroids like prednisolone can cause hyperglycemia as a side effect.
• Based on the available information, it is unclear which one is more likely to cause hyperglycemia, but both statins and corticosteroids have been associated with an increased risk of hyperglycemia 2.

From the Research

Comparison of Hyperglycemia Risk

• Prednisolone, a glucocorticoid, is known to cause hyperglycemia as a major side effect, as stated in 3, 4, 5.
• The risk of hyperglycemia with prednisolone is well-documented, and guidelines have been established for managing hyperglycemia in patients taking prednisolone 3, 5.
• In contrast, there is no evidence provided in the studies to suggest that statins (HMG-CoA reductase inhibitors) are more likely to cause hyperglycemia than prednisolone.
• The studies focus on the management of hyperglycemia induced by prednisolone, with no mention of statins as a comparative risk factor 6, 7.

Management of Hyperglycemia

• The management of prednisolone-induced hyperglycemia involves insulin therapy, with guidelines recommending a body weight-based daily insulin dose 6, 7.
• The optimal treatment strategy may vary depending on the duration of treatment and the administration schedule of corticosteroids 4.
• Clinical variables such as weight, sex, HbA1c, and diabetes status can affect insulin requirements in patients with prednisolone-associated hyperglycemia 7.