Diet, Nutrition and Supplements: May 2023

Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes

A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials


Anastassios G. Pittas, M.D., MS, Tetsuya Kawahara, M.D., Ph.D., Rolf Jorde, M.D., Ph.D., Bess Dawson-Hughes, M.D., Ellen M. Vickery, MS, Edith Angellotti, M.D., Jason Nelson, MPH, Thomas A. Trikalinos, M.D., and Ethan M. Balk, M.D., MPH


February 7, 2023 (Annals of Internal Medicine)



The role of vitamin D in people who are at risk for type 2 diabetes remains unclear.


To evaluate whether administration of vitamin D decreases risk for diabetes among people with prediabetes.

Data Sources:

PubMed, Embase, and from database inception through 9 December 2022.

Study Selection:

Eligible trials that were specifically designed and conducted to test the effects of oral vitamin D versus placebo on new-onset diabetes in adults with prediabetes.

Data Extraction:

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]).


Studies of people with prediabetes do not apply to the general population. Trials may not have been powered for safety outcomes.


In adults with prediabetes, vitamin D was effective in decreasing risk for diabetes.

Primary Funding Source:

None. (PROSPERO: CRD42020163522)


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