
Longitudinal observational studies show consistent inverse associations between vitamin D status, as measured by blood 25(OH)D level, and type 2 diabetes risk. There are three trials designed and conducted to test whether vitamin D reduces diabetes risk in adults with high-risk prediabetes: the Tromsø study in Norway with 511 participants, the vitamin D and type 2 diabetes (D2d) study in the U.S. with 2423 participants, and the Diabetes Prevention with active Vitamin D study (DPVD) study in Japan with 1256 participants. Vitamin D reduced the risk of developing diabetes compared to the placebo to a nearly identical degree in all three trials. The hazard ratio for vitamin D vs. placebo was 0.90 (95%CI 0.69 to 1.18) in Tromsø, 0.88 (95%CI 0.75 to 1.04) in D2d, and 0.87 (95%CI 0.67 to 1.17) in DPVD. The relative risk reductions were smaller than each trial was powered to detect (25 to 30%). A meta-analysis of individual participant data from these three trials showed that vitamin D reduced the risk of progression from prediabetes to diabetes by 15% (hazard ratio 0.85; 95% CI 0·75 to 0·96). Three other meta-analyses that combined aggregate data from these three trials and smaller, short-term trials that reported the effect of vitamin D on diabetes risk found similar reductions in diabetes risk with vitamin D in adults with prediabetes. In addition to its effect on diabetes prevention, trial-based evidence shows that vitamin D promotes regression to normal glucose regulation (NGR). In a recent meta-analysis that combined aggregated data from ten trials that reported the effect of vitamin D on regression to NGR, vitamin D increased the likelihood of regression to NGR by 27 percent (relative risk 1.27 [95%CI 1.12 to 1.45]) without heterogeneity among the trials. Based on the evidence, the 2024 Endocrine Society Guideline on Vitamin D for the Prevention of Disease recommends empiric vitamin D in adults with high-risk prediabetes to reduce progression to diabetes. The optimal dose of vitamin D and 25(OH)D level for diabetes risk reduction are not yet clear. The trials used varying dosages of vitamin D, from 842 to 7543 IU daily equivalent (weighted average, approximately 3500 IU per day), higher than the Recommended Daily Allowance. Further research, including treat-to-target trials, is needed to define optimal blood 25(OH)D levels for diabetes prevention.