Effect of active vitamin D treatment on development of type 2 diabetes: DPVD randomised controlled trial in Japanese population. (25th May 2022)

• Record Type: Journal Article
• Authors: Kawahara, Tetsuya; Suzuki, Gen; Mizuno, Shoichi; Inazu, Tetsuya; Kasagi, Fumiyoshi; Kawahara, Chie; Okada, Yosuke; Tanaka, Yoshiya
• Is Part Of: BMJ. Volume 377(2022)
• Publication Date: 2022-05-25
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Medicine; Periodicals; 610
• DOI: 10.1136/bmj-2021-066222
• Languages: English
• ISSNs: 0007-1447

Abstract

Abstract: Objective: To assess whether eldecalcitol, an active vitamin D analogue 2, 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.