• Ronald B Goldberg, Vanita R Aroda, David A Bluemke, Elizabeth Barrett-Connor, Matthew Budoff, Jill P Crandall, Dana Dabelea, Edward S Horton, Kieren J Mather, Trevor J Orchard, David Schade, Karol Watson, Marinella Temprosa, and Diabetes Prevention Program Research Group.
• From Diabetes Research Institute, University of Miami Miller School of Medicine, FL (R.B.G.); MedStar Health Research Institute, Washington, DC (V.R.A.); National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Washington, DC (D.A.B.); University of California, San Diego (E.B.-C.); Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles (M.B.); Albert Einstein College of Medicine, New York, NY (J.P.C.); University of Colorado Denver (D.D.); Joslin Diabetes Center, Boston, MA (E.S.H.); Indiana University School of Medicine, Indianapolis (K.J.M.); University of Pittsburgh Medical Center, PA (T.J.O.); University of New Mexico School of Medicine, Albuquerque (D.S.); University of California Los Angeles School of Medicine (K.W.); and George Washington University Biostatistics Center, Department of Epidemiology and Biostatistics, Rockville, MD (M.T.). dppmail@bsc.gwu.edu.
• Circulation. 2017 Jul 4; 136 (1): 52-64.

BackgroundDespite the reduced incidence of coronary heart disease with intensive risk factor management, people with diabetes mellitus and prediabetes remain at increased coronary heart disease risk. Diabetes prevention interventions may be needed to reduce coronary heart disease risk. This approach was examined in the DPP (Diabetes Prevention Program) and the DPPOS (Diabetes Prevention Program Outcome Study), a long-term intervention study in 3234 subjects with prediabetes (mean±SD age, 64±10 years) that showed reduced diabetes risk with lifestyle and metformin compared with placebo over 3.2 years.MethodsThe DPPOS offered periodic group lifestyle sessions to all participants and continued metformin in the originally randomized metformin group. Subclinical atherosclerosis was assessed in 2029 participants with coronary artery calcium (CAC) measurements after an average of 14 years of follow-up. The CAC scores were analyzed continuously as CAC severity and categorically as CAC presence (CAC score >0) and reported separately in men and women.ResultsThere were no CAC differences between lifestyle and placebo intervention groups in either sex. CAC severity and presence were significantly lower among men in the metformin versus the placebo group (age-adjusted mean CAC severity, 39.5 versus 66.9 Agatston units, P=0.04; CAC presence, 75% versus 84%, P=0.02), but no metformin effect was seen in women. In multivariate analysis, the metformin effect in men was not influenced by demographic, anthropometric, or metabolic factors; by the development of diabetes mellitus; or by use/nonuse of statin therapy.ConclusionsMetformin may protect against coronary atherosclerosis in prediabetes and early diabetes mellitus among men.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00038727.© 2017 American Heart Association, Inc.

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