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Improving diabetes prevention with benefit based tailored treatment: risk based reanalysis of Diabetes Prevention Program

BMJ 2015; 350 doi: (Published 19 February 2015) Cite this as: BMJ 2015;350:h454
  1. Jeremy B Sussman, research scientist1, assistant professor2,
  2. David M Kent, professor of medicine and director3,
  3. Jason P Nelson, statistician3,
  4. Rodney A Hayward, professor of medicine124
  1. 1Department of Veterans Affairs Center for Clinical Management Research, Ann Arbor, MI 48109-2800, USA
  2. 2Division of General Internal Medicine, University of Michigan, NCRC, 2800 Plymouth Road, Building 16/343E, Ann Arbor
  3. 3Predictive Analytics and Comparative Effectiveness Center, Tufts Medical Center, 35 Kneeland Street, Boston, MA 02111, USA
  4. 4RWJ Foundation Clinical Scholars Program, University of Michigan, 2800 Plymouth Road, NCRC B10-G016, Ann Arbor
  1. Correspondence to J B Sussman, 2800 Plymouth Road, North Campus Research Complex, Building 16, Room 335E, Ann Arbor, MI 48109-2800, USA jeremysu{at}
  • Accepted 26 November 2014


Objective To determine whether some participants in the Diabetes Prevention Program were more or less likely to benefit from metformin or a structured lifestyle modification program.

Design Post hoc analysis of the Diabetes Prevention Program, a randomized controlled trial.

Setting Ambulatory care patients.

Participants 3060 people without diabetes but with evidence of impaired glucose metabolism.

Intervention Intervention groups received metformin or a lifestyle modification program with the goals of weight loss and physical activity.

Main outcome measure Development of diabetes, stratified by the risk of developing diabetes according to a diabetes risk prediction model.

Results Of the 3081 participants with impaired glucose metabolism at baseline, 655 (21%) progressed to diabetes over a median 2.8 years’ follow-up. The diabetes risk model had good discrimination (C statistic=0.73) and calibration. Although the lifestyle intervention provided a sixfold greater absolute risk reduction in the highest risk quarter than in the lowest risk quarter, patients in the lowest risk quarter still received substantial benefit (three year absolute risk reduction 4.9% v 28.3% in highest risk quarter; numbers needed to treat of 20.4 and 3.5, respectively). The benefit of metformin, however, was seen almost entirely in patients in the top quarter of risk of diabetes. No benefit was seen in the lowest risk quarter. Participants in the highest risk quarter averaged a 21.4% three year absolute risk reduction (number needed to treat 4.6).

Conclusions Patients at high risk of diabetes have substantial variation in their likelihood of receiving benefit from diabetes prevention treatments. Using this knowledge could decrease overtreatment and make prevention of diabetes far more efficient, effective, and patient centered, provided that decision making is based on an accurate risk prediction tool.


  • The Diabetes Prevention Program study was conducted by the Diabetes Prevention Program Investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The data from Diabetes Prevention Program reported here were supplied by the NIDDK Central Repositories. This manuscript was not prepared in collaboration with investigators of the Diabetes Prevention Program study and does not necessarily reflect the opinions or views of the Diabetes Prevention Program Investigators, the NIDDK Central Repositories, or the NIDDK.

  • Contributors: DMK initially proposed the study. All authors contributed to the study design, planning the data analysis, and interpreting the data. JBS wrote the initial manuscript, and all authors contributed to improving the manuscript. JBS is the guarantor.

  • Funding: Support for this study was provided by the Patient-Centered Outcomes Research Institute (PCORI: 1IP2PI000722). Additional support was provided by the National Institute of Neurological Disorders and Stroke (U01 AA022802), the Department of Veterans Affairs Quality Enhancement Research Initiative (QUERI DIB 98-001), and the Michigan Center for Diabetes Translational Research (National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (P60 DK-20572)).

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the institutional review board at the Tufts Medical Center.

  • Transparency declaration: The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

  • Data sharing: Information on the process of obtaining the study dataset is available at the NIDDK Repository website ( The dataset and technical appendix can be obtained by submitting of a formal request to the NIDDK Repository. Requests for the statistical code can be submitted to jnelson2{at}

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