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

Abstract

Objective: Several 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 methods: During 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.

Results: At 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.

Conclusions: In 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 number: NCT00038727; Results.

Keywords: Hmg Coa reductase inhibitors; lipids; pre-diabetes.

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1

Cumulative incidence of statin initiation by treatment group.

Figure 2

Diabetes hazard rates by number of visits with reported statin use. The risk of developing diabetes associated with the duration of exposure to statin therapy estimated using Cox proportional hazards models. The symbol on each line indicates the expected hazard rate for a subject with a number of visits with reported statin therapy equal to the mean value for the group over the group-specific range (5th–95th percentile). The risk for progression to diabetes by number of visits with reported statin use was calculated for each treatment group with model 5 from table 2. The number of semiannual visits with reported statin use significantly predicted progression to diabetes only in the lifestyle group (p=0.007); this relationship was not significantly different across the three groups (heterogeneity p=0.26).