Vitamin D Supplementation and Risk of Type 2 Diabetes in Patients with Prediabetes: A Meta-analysis of Individual Participant Data from Randomized, Placebo-Controlled Trials

Background: Individual randomized clinical trials have not shown conclusively that taking vitamin D can prevent type 2 diabetes. Methods: We conducted a systematic review and meta-analysis of individual participant-level data to determine whether vitamin D supplementation lowers the risk of diabetes in people with prediabetes. Trials published through February 12, 2021, that compared oral vitamin D supplementation (alone) with placebo over a minimum 2-year follow up, and had new-onset diabetes as a primary outcome were included. Proportional hazards models were used to analyze individual participant data, with pre-specified intention-to-treat (ITT) and per-protocol analyses, without and after adjustment for baseline age, gender, BMI, race and hemoglobin A1c. Safety was also assessed. Results: Three trials were eligible (testing D3 20,000 IU/week [Tromsø], D3 4,000 IU/day [D2d], and eldecalcitol 0.75 μg/day [DPVD] vs. matching placebos) and contributed data from 4190 randomized participants (mean age 60.4 years, 44.2% women). After a median 3.0 years of follow-up, new-onset diabetes occurred in 475/2097 participants assigned to vitamin D and 524/2093 assigned to placebo (8.42 and 9.50 events per 100 person-years, respectively). The unadjusted hazard ratio (95% CI) for vitamin D was 0.88 (0.77 to 0.99) in the ITT and 0.85 (0.75 to 0.97) in the per-protocol analyses. Adjusted hazard ratios were 0.85 (0.75 to 0.96) in the ITT and 0.83 (0.73 to 0.94) in the per-protocol analyses. There was no evidence of heterogeneity of treatment effect among the three trials. The incidence of hypercalcemia, hypercalciuria, or kidney stones did not differ between the vitamin D and placebo groups. Conclusion: In adult patients with prediabetes, vitamin D supplementation is safe and effective for lowering the risk of diabetes by about 15%. Disclosure A. G. Pittas: None. T. Kawahara: None. R. Jorde: None. J. P. Nelson: None. E. Angellotti: None. E. Vickery: None. B. Dawson-hughes: None. T. Trikalinos: None. E. M. Balk: None. Funding American Diabetes Association (1-14-D2D-01 to A.G.P.); National Institutes of Health (U01DK098245)