Clinician Article

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.

  • Pittas AG
  • Kawahara T
  • Jorde R
  • Dawson-Hughes B
  • Vickery EM
  • Angellotti E, et al.
Ann Intern Med. 2023 Mar;176(3):355-363. doi: 10.7326/M22-3018. Epub 2023 Feb 7. (Review)
PMID: 36745886
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  • Endocrine
    Relevance - 6/7
    Newsworthiness - 6/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 6/7
    Newsworthiness - 5/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 6/7
    Newsworthiness - 5/7
  • Internal Medicine
    Relevance - 5/7
    Newsworthiness - 6/7


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

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

DATA SOURCES: PubMed, Embase, and ClinicalTrials.gov 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]).

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

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


Clinical Comments


Well done meta-analysis from high-quality RCTs providing compelling evidence that high-dose Vitamin D can reduce progression to type 2 diabetes in high-risk patients.

Family Medicine (FM)/General Practice (GP)

Fascinating that higher-dose supplementation helps prevent diabetes in those with prediabetes. May have to rethink my practice.

General Internal Medicine-Primary Care(US)

More research is needed, but this seems like a low-stakes intervention to decrease diabetes risk.

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