Effect of Vitamin D on Regression to Normal Glucose Regulation in Adults With Prediabetes

Meta-analyses of clinical trials have shown that vitamin D lowers the risk of progression from prediabetes to diabetes. Less is known about whether vitamin D promotes regression to normal glucose regulation (NGR). We conducted a systematic review and meta-analysis of clinical trials with vitamin D in adults with prediabetes that have reported on the outcome of regression to NGR. We searched Medline (through PubMed), Embase, and the trial registry ClinicalTrials.gov from inception to July 3, 2024, for randomized, controlled trials of at least 6 months' duration that reported on the effects of oral vitamin D supplementation on NGR in adults with prediabetes. The search identified 10 eligible trials, involving 4478 participants. The baseline characteristics of the study cohorts were: mean age range 20 to 74 years, mean body mass index range 24 to 38, mean blood 25-hydroxyvitamin D range 12 to 28 ng/mL. The median study duration range was 0.5 to 5 years. Across trials, 416 of 2253 (18.5%) participants randomly assigned to vitamin D reached NGR vs 312 of 2225 (14.0%) participants randomly assigned to placebo. In all trials, the relative risk of regression to NGR favored the vitamin D group, ranging from 1.09 to 12.6. After combining data, the summary relative risk of regression to NGR for vitamin D vs placebo was 1.27 (95% CI, 1.12-1.45), with no heterogeneity (I = 1%). Sensitivity analyses did not change the result. Participant-level variables were not available, limiting meaningful subgroup analyses. In conclusion, vitamin D increases the likelihood of regression to normoglycemia in adults with prediabetes.