Use of the vitamin D analogue eldecalcitol could potentially reduce the development of type 2 diabetes based on the findings of a recent RCT
Eldecalcitol, a vitamin D analogue, could prevent the development of overt type 2 diabetes in patients with impaired glucose tolerance although more data are required. This was the finding from a randomised, placebo-controlled trial by a team of Japanese researchers.
In 2017, it was estimated that globally, there were approximately 462 million individuals with type 2 diabetes ( 6.3% of the world’s population) and over 1 million deaths per year attributed to the disorder. Pre-diabetes is best described as an intermediate metabolic state between normoglycaemia and diabetes that is characterised by impaired glucose tolerance and impaired fasting glucose. Moreover, the presence of impaired glucose tolerance is associated with an increased risk of cardiovascular disease.
The potential role of vitamin D in diabetes has been suggested by the evidence that insulin secreting cells are able to not only produce but respond to the natural hormone 1-alpha, 25-Dihydroxyvitamin D3. In addition, low plasma 25-hydroxyvitamin D levels are associated with increased risk of type 2 diabetes in the general population. Furthermore, a systemic review and meta-analysis has revealed how in people with impaired glucose tolerance, vitamin D supplementation reduces the risk of type 2 diabetes and increases the reversion rate to normoglycaemia. Despite this, other studies have found that supplementation with vitamin D in patients who are not deficient in the vitamin is unlikely to prevent progression from pre-diabetes to diabetes.
With uncertainty over the value of vitamin D supplementation in those with impaired glucose tolerance, the present study undertook a randomised, placebo-controlled trial with eldecalcitol, a vitamin D analogue. The aim was to determine if eldecalcitol (which is used in Japan as a treatment for the prevention of osteoporosis) at a dose of 75mcg/day to patients with impaired glucose tolerance could prevent the development of type 2 diabetes.
Enrolled participants had a fasting glucose level < 126mg/dl and a glycated haemoglobin of < 6.5%. The primary outcome was the development of type 2 diabetes defined by either a glycated haemoglobin > 6.5% and a fasting glucose concentration > 200mg/dl. The main secondary outcome was regression to normoglycaemia.
Eldecalcitol and development of type 2 diabetes
A total of 1256 participants with a mean age of 61.3 years (44.5% female) were randomised to eldecalcitol (630) or placebo and followed for a median of 2.9 years. Among participants, the mean baseline 25-hydroxyvitamin D concentration was 20.9ng/ml.
During the follow-up period, 12.5% of those in the eldecalcitol group and 14.2% of those assigned to placebo developed type 2 diabetes (hazard ratio, HR = 0.87, 95% CI 0.67 – 1.17, p = 0.39), representing a non-significant difference. The proportion of patients regressing to normoglycaemia was also similar and not significantly different (HR = 1.15, 95% CI 0.93 – 1.41, P = 0.21).
Interestingly, when the researchers undertook a regression analysis that adjusted for 11 pre-specified covariates including age, sex, body mass index, glycated haemoglobin, they found that eldecalcitol was effective for the prevention of type 2 diabetes (HR = 0.69, 95% CI 0.51 – 0.95, p = 0.02).
They concluded that while eldecalcitol did not significantly reduce the incidence of type 2 diabetes or the level of regression to normoglycaemia, after adjustment for confounders, the drug was found to be effective at reducing the incidence of diabetes. As a result, it could be possible that eldecalcitol prevents the development of type 2 diabetes and they called for further work to examine their findings in more detail.
Kawahara T el al. Effect of active vitamin D treatment on development of type 2 diabetes: DPVD randomised controlled trial in Japanese population BMJ 2022