Which lipid-lowering agent is associated with an increased risk for developing type 2 diabetes?

From the Guidelines

Statins are the lipid-lowering agents most strongly associated with an increased risk for developing type 2 diabetes. This association is supported by a meta-analysis of 13 statin trials, which reported a 9% higher type 2 diabetes risk over four years with standard-dose statin therapy, and an even greater risk with intensive statin therapy 1. The risk of developing type 2 diabetes with statins appears to be dose-dependent, with higher-intensity regimens carrying a greater risk than lower-intensity ones. Key factors that contribute to this risk include pre-existing risk factors for diabetes, such as obesity, family history, or elevated fasting glucose levels.

Some of the key points to consider regarding the association between statins and the risk of type 2 diabetes include:

• The mechanism behind this association is not fully understood but may involve decreased insulin sensitivity, reduced insulin secretion from pancreatic beta cells, and impaired glucose uptake in peripheral tissues.
• Despite the increased risk of diabetes, the cardiovascular benefits of statin therapy generally outweigh this risk in patients with established cardiovascular disease or those at high risk, with one CVD event prevented for each 100–150 people treated with a statin, while 500 people must be treated to cause one new case of type 2 diabetes 1.
• Patients taking statins should have their blood glucose monitored periodically, especially those with pre-existing risk factors for diabetes.
• It's worth noting that similar risks have not been observed with non-statins, except for niacin, suggesting that the choice of lipid-lowering therapy could be influenced by the patient's diabetes risk profile 1.

From the Research

Lipid-Lowering Agents and Type 2 Diabetes Risk

• The association between lipid-lowering agents and the risk of developing type 2 diabetes has been investigated in several studies 2, 3, 4, 5, 6.
• Statins, a class of lipid-lowering agents, have been shown to increase the risk of developing type 2 diabetes 2, 4.
• A network meta-analysis found that statins, as a class, significantly increased the likelihood of developing diabetes by 12% 4.
• Specific statins, such as atorvastatin and rosuvastatin, have been associated with a higher risk of developing diabetes compared to other statins 4.
• In contrast, ezetimibe, a cholesterol-absorption inhibitor, has been shown to improve glucose metabolism in patients with type 2 diabetes 6.
• The mechanisms underlying the association between statins and type 2 diabetes risk are not fully understood, but may involve changes in insulin sensitivity and glucose metabolism 3, 5.

Statin-Specific Risks

• Atorvastatin 80mg has been associated with the highest risk of diabetes, with an odds ratio of 1.34 4.
• Rosuvastatin has also been associated with an increased risk of diabetes, with an odds ratio of 1.17 4.
• Simvastatin and pravastatin have been associated with a lower risk of diabetes compared to atorvastatin and rosuvastatin 4.
• The risk of diabetes associated with statin use may be dose-dependent, with higher doses of statins associated with a greater risk of diabetes 4.

Clinical Implications

• The association between statins and type 2 diabetes risk should be considered when prescribing lipid-lowering therapy, particularly for patients at high risk of diabetes 2, 4.
• Patients taking statins should be monitored for changes in glucose metabolism and diabetes risk factors 3, 5.
• Alternative lipid-lowering agents, such as ezetimibe, may be considered for patients at high risk of diabetes or those who experience adverse effects with statin therapy 6.