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.
- Hmg Coa reductase inhibitors
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Contributors JPC, KM, RBG and KW researched the data, edited and reviewed the manuscript, and contributed to discussion. SNR wrote the manuscript and researched the data. SF contributed to discussion. RR and EB-C researched the data and contributed to discussion. MT researched the data, edited and reviewed the manuscript, contributed to discussion, and analyzed the data.
Funding During the DPP and DPPOS, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the Coordinating Center for the design and conduct of the study, and collection, management, analysis and interpretation of the data (U01 DK048489). The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Funding was also provided by the National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart Lung and Blood Institute, the Office of Research on Women’s Health, the National Institute on Minority Health and Health Disparities, the Centers for Disease Control and Prevention, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided additional funding and material support during the DPP, Lipha (Merck-Sante) provided medication, and LifeScan donated materials during the DPP and DPPOS. This research was also supported, in part, by the intramural research program of the NIDDK. LifeScan, Health O Meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck and Co, Nike Sports Marketing, Slim Fast Foods and Quaker Oats donated materials, equipment or medicines for concomitant conditions. McKesson BioServices, Matthews Media Group and the Henry M Jackson Foundation provided support services under subcontract with the Coordinating Center.
Competing interests None declared.
Ethics approval IRB for George Washington University and the IRBs of each of the participating centers.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement In accordance with the NIH Public Access Policy, we continue to provide all manuscripts to PubMed Central, including this manuscript. DPP/DPPOS has provided the protocols and lifestyle and medication intervention manuals to the public through its public website (https://www.dppos.org). The DPPOS abides by the NIDDK data sharing policy and implementation guidance as required by the NIH/NIDDK (https://www.niddkrepository.org/studies/dppos/).
Author note MT is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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