Eldecalcitol, a vitamin D analog, is not associated with a reduced incidence of type 2 diabetes among adults with prediabetes, though it may have a beneficial effect in those with lower insulin secretion, according to study data.

Tetsuya Kawahara

“We were surprised at the findings because our pilot study showed eldecalcitol’s preventive effect on the development of type 2 diabetes,” Tetsuya Kawahara, MD, PhD, of the University of Occupational and Environment Health and Shin Komonji Hospital in Kitakyushu, Japan, told Healio. “We think that these findings are a result of lack of statistical power, an unbalanced distribution of 2-hour plasma glucose concentrations between participants in the eldecalcitol and placebo groups, or both. Treatment with eldecalcitol was effective in increasing bone mineral densities and serum osteocalcin concentrations.”

Kawahara and colleagues conducted a randomized, double-blind, placebo-controlled trial in 1,256 adults aged 30 years or older with impaired glucose tolerance in Japan (45.5% women; mean age, 61.3 years). Participants were randomly assigned to 0.75 g of eldecalcitol daily (n = 630) or placebo (n = 626) for 3 years. Study visits took place at 3-month intervals and included a routine clinical exam, a 75 g oral glucose tolerance test, collection of serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels and a measurement of BMD. The primary endpoint was the development of type 2 diabetes from baseline to 3 years.

The findings were published in The BMJ.

During the follow-up period, 79 adults in the eldecalcitol group and 89 in the placebo group developed diabetes. There was no significant difference in diabetes incidence between the two groups. There was also no difference in the percentage of participants achieving normoglycemia.

Eldecalcitol lowers diabetes risk in adults with low insulin secretion

In post hoc analysis, participants were divided into tertiles based on homoeostasis model assessment beta-cell function, HOMA of insulin resistance and fasting immunoreactive insulin levels. Adults in the lowest tertiles for all three metrics taking eldecalcitol had a lower risk for developing type 2 diabetes compared with placebo.

“Although treatment with eldecalcitol did not significantly reduce the incidence of diabetes among people with prediabetes, the results suggested the potential for a beneficial effect of eldecalcitol on people with insufficient insulin secretion,” Kawahara said.

Serum 1,25-dihydroxyvitamin D and bone alkaline phosphate levels were significantly lower in the eldecalcitol group compared with placebo, and those taking eldecalcitol had higher BMD of the lumbar spine and femoral neck than those taking placebo

Larger intervention studies needed

In a related editorial, Tatiana Christides, MD, PhD, senior lecturer in medical sciences at Barts and the London School of Medicine and Dentistry, Queen Mary University in London, fellow of the Royal Society of Medicine and president emeritus of the Royal Society of Medicine Food and Health Forum, said she was not surprised that there was no difference between the two groups in diabetes incidence rates, though the findings were still disappointing.

“We have now seen, for multiple medical conditions, that clinical intervention studies looking for an effect of vitamin D supplementation on disease do not support epidemiological evidence showing an association of low vitamin D status with the disease,” Christides told Healio. “I think vitamin D is the ‘poster child’ for making people aware that association does not mean causation.”

Both Christides and Kawahara noted the study was underpowered to detect the small difference in type 2 diabetes groups. Additionally, Christides said the study findings may differ in other populations and lack data on the degree of vitamin D deficiency in participants.

“What we now need are larger intervention studies well powered to detect a small, but clinically meaningful, decrease in progression risk, carried out in younger and diverse populations,” Christides said. “We also need to know if vitamin D status including degree of deficiency interacts with supplementation response to progression risk.”