From the Guidelines
Statin therapy can cause insulin resistance in some patients, as evidenced by a moderate dose-dependent increase in new diagnoses of diabetes, particularly in individuals with baseline glycaemic markers close to the diagnostic threshold for diabetes. This effect is supported by a recent individual participant data meta-analysis published in The Lancet Diabetes and Endocrinology 1, which found that statin therapy causes a small but significant increase in the risk of developing insulin resistance and new-onset diabetes mellitus. The mechanism involves statins interfering with glucose metabolism by decreasing insulin sensitivity in peripheral tissues and potentially reducing insulin secretion from pancreatic beta cells.
Key points to consider:
- Statins, including medications like atorvastatin, rosuvastatin, simvastatin, and pravastatin, have been associated with this increased risk, with higher doses carrying greater risk 1.
- Despite this risk, the cardiovascular benefits of statins generally outweigh the diabetes risk for most patients who need them for cardiovascular disease prevention 1.
- Patients taking statins, especially those with pre-existing risk factors for diabetes (obesity, family history, metabolic syndrome), should have their blood glucose levels monitored periodically 1.
- Healthcare providers may consider using less diabetogenic statins like pravastatin or lower doses when treating patients with multiple diabetes risk factors 1.
In terms of management, it is essential to balance the benefits of statin therapy with the potential risk of insulin resistance and new-onset diabetes. As recommended by the standards of care in diabetes-2024, statin therapy may increase the risk of type 2 diabetes in people at high risk of developing type 2 diabetes, and glucose status should be monitored regularly in such individuals 1. However, it is not recommended that statins be discontinued for this adverse effect, and instead, diabetes prevention approaches should be reinforced 1.
From the Research
Statin Therapy and Insulin Resistance
- Statin therapy has been shown to have both positive and negative effects on insulin sensitivity and secretion 2, 3, 4, 5, 6.
- A study published in 2006 found that atorvastatin (10 mg/day) improved insulin sensitivity in insulin-resistant, non-diabetic subjects 2.
- However, other studies have suggested that statin therapy may worsen insulin resistance and increase the risk of developing type 2 diabetes 3, 4, 6.
- A 2021 study found that atorvastatin (40 mg daily) increased insulin resistance and insulin secretion in adults without known atherosclerotic cardiovascular disease or type 2 diabetes 4.
- Another study published in 2010 found that insulin-resistant patients had a greater response to statin therapy, with increased LDL cholesterol reduction 5.
Mechanisms of Statin-Induced Insulin Resistance
- The mechanisms by which statins induce insulin resistance are not fully understood, but may involve impaired Ca2+ signaling in pancreatic β-cells, down-regulation of GLUT-4 in adipocytes, and compromised insulin signaling 6.
- Statins may also impact epigenetics, contributing to statin-induced type 2 diabetes via differential expression of microRNAs 6.
- The weight of clinical evidence suggests that statins have a worsening effect on insulin resistance and secretion, although the cardiovascular benefits of statin therapy outweigh the risk of developing insulin resistance 3.
Clinical Implications
- Clinicians should consider diabetes monitoring in patients receiving statin therapy to ensure early diagnosis and appropriate management 6.
- Patients with features of the metabolic syndrome, such as high triglycerides and low HDL cholesterol, may have an enhanced benefit from statin therapy 5.
- The clinical benefit of statin therapy is directly proportional to the achieved percent reduction in LDL cholesterol, and insulin-resistant patients may have a greater response to statin therapy 5.