From the Guidelines
Statin medications can potentially increase the risk of developing diabetes through several mechanisms, including impairing insulin secretion and reducing insulin sensitivity, and this risk is generally considered small compared to the cardiovascular benefits of statins. The most recent and highest quality study on this topic, published in The Lancet Diabetes and Endocrinology in 2024 1, found that statin therapy causes a moderate dose-dependent increase in new diagnoses of diabetes, with the majority of new diagnoses occurring in people with baseline glycaemic markers close to the diagnostic threshold for diabetes. Some of the key mechanisms by which statins may increase the risk of diabetes include:
- Impairing insulin secretion from pancreatic beta cells
- Reducing insulin sensitivity in muscle and fat tissues
- Interfering with glucose transport into cells by affecting GLUT4 transporters
- Increasing insulin resistance
- Decreasing the production of a protein called adiponectin, which normally helps regulate glucose metabolism
- Possibly damaging pancreatic beta cells directly, reducing their ability to produce insulin The risk of diabetes associated with statin use is considered small compared to the cardiovascular benefits of statins, especially in patients with established heart disease or high cardiovascular risk 1. However, patients taking statins should have their blood glucose levels monitored regularly, particularly those with existing risk factors for diabetes such as obesity, family history of diabetes, or prediabetes 1. It is not recommended that statins be discontinued due to the risk of diabetes, as the cardiovascular benefits of statins outweigh this risk 1. Instead, glucose status should be monitored regularly and diabetes prevention approaches reinforced in individuals at high risk of developing type 2 diabetes who are taking statins 1.
From the Research
Mechanisms of Statin-Associated Diabetes Risk
- Statin medications are associated with a modest excess of type 2 diabetes mellitus, with high-intensity statins posing a higher risk than moderate-intensity statins 2
- The proposed mechanisms for statin-associated diabetes risk include increased insulin resistance or impaired insulin secretion 2
- Genetic polymorphisms with reduced HMG CoA reductase function are associated with weight gain, insulin resistance, and diabetes 2
- Animal models have shown that HMG CoA inhibition has multiple downstream effects that may increase diabetes risk, including statin impairment of insulin signaling, decreased adipocyte differentiation, and decreased pancreatic β-cell insulin secretion 2
Effects of Statins on Insulin Resistance and Secretion
- Statin treatment increases insulin resistance and insulin secretion, as demonstrated by a clinical trial of atorvastatin 40 mg daily in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline 3
- The study found that atorvastatin increased insulin resistance by a median of 8% and insulin secretion by a median of 9% compared to baseline 3
- The risk of new-onset diabetes with statin use may increase in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion 3
Clinical Implications of Statin-Associated Diabetes Risk
- The excess risk of diabetes associated with statin use appears to be confined to those who are already at risk for developing diabetes 2
- Diabetes is diagnosed only 2-4 months earlier in statin-treated patients, and the clinical impact of statin-associated diabetes is likely unimportant 2
- The cardiovascular risk reduction benefit from statin use far outweighs the potential for adverse effects in all but the very lowest risk individuals 2, 4
- The benefits of statins in reducing cardiovascular events clearly outweigh the risk of diabetes, despite the diabetogenicity of different statins 4