PubMed, Embase, and ClinicalTrials.gov from database inception through 9 December 2022.
STUDY SELECTION: The primary outcome was time to event for new-onset diabetes. Secondary outcomes were regression to normal
glucose regulation and adverse events. Prespecified analyses (both unadjusted and adjusted for key baseline variables) were conducted according to the intention-to-treat principle.
DATA SYNTHESIS: Three randomized trials were included, which tested
cholecalciferol, 20 000 IU (500 mcg) weekly;
cholecalciferol, 4000 IU (100 mcg) daily; or
eldecalcitol, 0.75 mcg daily, versus matching
placebos. Trials were at low risk of bias.
Vitamin D reduced risk for diabetes by 15% (hazard ratio, 0.85 [95% CI, 0.75 to 0.96]) in adjusted analyses, with a 3-year absolute risk reduction of 3.3% (CI, 0.6% to 6.0%). The effect of
vitamin D did not differ in prespecified subgroups. Among participants assigned to the
vitamin D group who maintained an intratrial mean serum
25-hydroxyvitamin D level of at least 125 nmol/L (≥50 ng/mL) compared with 50 to 74 nmol/L (20 to 29 ng/mL) during follow-up,
cholecalciferol reduced risk for diabetes by 76% (hazard ratio, 0.24 [CI, 0.16 to 0.36]), with a 3-year absolute risk reduction of 18.1% (CI, 11.7% to 24.6%).
Vitamin D increased the likelihood of regression to normal
glucose regulation by 30% (rate ratio, 1.30 [CI, 1.16 to 1.46]). There was no evidence of difference in the rate ratios for adverse events (
kidney stones: 1.17 [CI, 0.69 to 1.99];
hypercalcemia: 2.34 [CI, 0.83 to 6.66];
hypercalciuria: 1.65 [CI, 0.83 to 3.28]; death: 0.85 [CI, 0.31 to 2.36]).
LIMITATIONS: None. (PROSPERO: CRD42020163522).