Statin use and risk of developing diabetes: results from the Diabetes Prevention Program

Abstract

ObjectiveSeveral clinical trials of cardiovascular disease prevention with statins have reported increased risk of type 2 diabetes (T2DM) with statin therapy. However, participants in these studies were at relatively low risk for diabetes. Further, diabetes was often based on self-report and was not the primary outcome. It is unknown whether statins similarly modify diabetes risk in higher risk populations.Research design and methodsDuring the Diabetes Prevention Program Outcomes Study (n=3234), the long-term follow-up to a randomized clinical trial of interventions to prevent T2DM, incident diabetes was assessed by annual 75 g oral glucose tolerance testing and semiannual fasting glucose. Lipid profile was measured annually, with statin treatment determined by a participant’s own physician outside of the protocol. Statin use was assessed at baseline and semiannual visits.ResultsAt 10 years, the cumulative incidence of statin initiation prior to diabetes diagnosis was 33%–37% among the randomized treatment groups (p=0.36). Statin use was associated with greater diabetes risk irrespective of treatment group, with pooled HR (95% CI) for incident diabetes of 1.36 (1.17 to 1.58). This risk was not materially altered by adjustment for baseline diabetes risk factors and potential confounders related to indications for statin therapy.ConclusionsIn this population at high risk for diabetes, we observed significantly higher rates of diabetes with statin therapy in all three treatment groups. Confounding by indication for statin use does not appear to explain this relationship. The effect of statins to increase diabetes risk appears to extend to populations at high risk for diabetes.Trial registration numberNCT00038727; Results.

Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus

“…However, this is a pleiotropic class of drugs that also exerts several anti-inflammatory effects (43, 544). Despite these anti-inflammatory effects, several studies have now shown statin use to be associated with an increased risk for T2DM (89, 91, 381, 410). Furthermore, results from Cederberg et al suggest that statins reduce insulin sensitivity and insulin secretion (63).…”

Patterns of statin use and long‐term adherence and persistence among older adults with diabetes

“…However, older adults with diabetes may find adherence to statin therapy challenging due to many reasons, including polypharmacy, increased susceptibility to adverse events, and as a result of declining executive and cognitive functioning . There is strong evidence linking statins with increased risk of diabetes . Furthermore, among people with established diabetes, statin therapy has been associated with poor glycemic control, which could contribute to increased discontinuation or poor adherence.…”

“…17 There is strong evidence linking statins with increased risk of diabetes. 18 Furthermore, among people with established diabetes, statin therapy has been associated with poor glycemic control, 19 which could contribute to increased discontinuation or poor adherence.…”

Unexplained reciprocal regulation of diabetes and lipoproteins

“…Several years ago, it was revealed that statins, widely used for LDL lowering, are associated with a slightly higher risk of diabetes [2,3,4▪]. This risk is statin dose-dependent [5].…”