U.S. Department of Veterans Affairs



Anastassios G. Pittas, Tufts Medical CenterFollow
Bess Dawson‑Hughes, the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University
Patricia Sheehan, the Spaulding Rehabilitation Network, Charlestown
James H. Ware, Harvard School of Public Health
William C. Knowler, National Institute of Diabetes and Digestive and Kidney Diseases
Vanita R. Aroda, Brigham and Women’s Hospital
Irwin Brodsky, the Maine Medical Center
Lisa Ceglia, Tufts Medical Center
Chhavi Chadha, HealthPartners Institute, Minneapolis
Ranee Chatterjee, Duke University Medical Center, Durham
Cyrus Desouza, the University of Nebraska Medical Center and Omaha Veterans Affairs Medical Center
Rowena Dolor, Duke University Medical Center, Durham
John Foreyt, Baylor College of Medicine, Houston
Paul Fuss, Tufts Medical Center
Adline Ghazi, MedStar Good Samaritan Hospital, Baltimore
Daniel S. Hsia, Pennington Biomedical Research Center, Baton Rouge, LA
Karen C. Johnson, the University of Tennessee Health Science Center, Memphis
Sangeeta R. Kashyap, Cleveland Clinic, Cleveland
Sun Kim, Stanford University Medical Center, Stanford
Erin S. LeBlanc, Kaiser Permanente Center for Health Research–Northwest, Portland
Michael R. Lewis, the University of Vermont, Burlington
Emilia Liao, Northwell Health Lenox Hill Hospital, New York
Anne Peters, the Keck School of Medicine of the University of Southern California, Los Angeles
Lawrence S. Phillips, Emory University School of Medicine, Atlanta, and the Atlanta Veterans Affairs Medical Center
Richard Pratley, AdventHealth Translational Research Institute for Metabolism and Diabetes, Orlando
Philip Raskin, the University of Texas Southwestern Medical Center, Dallas
Neda Rasouli, the University of Colorado Denver and the Veterans Affairs Eastern Colorado Health Care System, Denver
David Robbins, the University of Kansas Medical Center, Kansas City
Clifford Rosen, Maine Medical Center Research Institute
Ellen M. Vickery, Tufts Medical Center
Myrlene Staten, the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda
Jason Nelson, Tufts Medical Center

Date of this Version


Document Type



2019 Massachusetts Medical Society


N Engl J Med 2019;381:520-30. DOI: 10.1056/NEJMoa1900906



Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown.


We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508.


A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups.


Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.)