Effect of active vitamin D treatment on development of type 2 diabetes: DPVD randomised controlled trial in Japanese population

BMJ. 2022 May 25:377:e066222. doi: 10.1136/bmj-2021-066222.


Objective: To assess whether eldecalcitol, an active vitamin D analogue2, can reduce the development of type 2 diabetes among adults with impaired glucose tolerance.

Design: Double blinded, multicentre, randomised, placebo controlled trial.

Setting: Three hospitals in Japan, between June 2013 and August 2019.

Participants: People aged 30 years and older who had impaired glucose tolerance defined by using a 75 g oral glucose tolerance test and glycated haemoglobin level.

Interventions: Participants were randomised to receive active vitamin D (eldecalcitol 0.75 μg per day; n=630) or matching placebo (n=626) for three years.

Main outcomes: The primary endpoint was incidence of diabetes. Prespecified secondary endpoints were regression to normoglycaemia and incidence of type 2 diabetes after adjustment for confounding factors at baseline. In addition, bone densities and bone and glucose metabolism markers were assessed.

Results: Of the 1256 participants, 571 (45.5%) were women and 742 (59.1%) had a family history of type 2 diabetes. The mean age of participants was 61.3 years. The mean serum 25-hydroxyvitamin D concentration at baseline was 20.9 ng/mL (52.2 nmol/L); 548 (43.6%) participants had concentrations below 20 ng/mL (50 nmol/L). During a median follow-up of 2.9 years, 79 (12.5%) of 630 participants in the eldecalcitol group and 89 (14.2%) of 626 in the placebo group developed type 2 diabetes (hazard ratio 0.87, 95% confidence interval 0.67 to 1.17; P=0.39). Regression to normoglycaemia was achieved in 145 (23.0%) of 630 participants in the eldecalcitol group and 126 (20.1%) of 626 in the placebo group (hazard ratio 1.15, 0.93 to 1.41; P=0.21). After adjustment for confounding factors by multivariable fractional polynomial Cox regression analysis, eldecalcitol significantly lowered the development of diabetes (hazard ratio 0.69, 0.51 to 0.95; P=0.020). In addition, eldecalcitol showed its beneficial effect among the participants with the lower level of basal insulin secretion (hazard ratio 0.41, 0.23 to 0.71; P=0.001). During follow-up, bone mineral densities of the lumbar spine and femoral neck and serum osteocalcin concentrations significantly increased with eldecalcitol compared with placebo (all P<0.001). No significant difference in serious adverse events was observed.

Conclusions: Although treatment with eldecalcitol did not significantly reduce the incidence of diabetes among people with pre-diabetes, the results suggested the potential for a beneficial effect of eldecalcitol on people with insufficient insulin secretion.

Trial registration: UMIN Clinical Trials Registry UMIN000010758.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Double-Blind Method
  • Female
  • Glucose Intolerance* / drug therapy
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Prediabetic State*
  • Vitamin D


  • Vitamin D