Vitamin D supplementation and adverse skeletal and non-skeletal outcomes in individuals at increased cardiovascular risk: Results from the International Polycap Study (TIPS)-3 randomized controlled trial.

BACKGROUND AND AIMS: Vitamin D has mostly been tested in Western populations. We examined the effect of high dose vitamin D in a population drawn predominantly from outside of Western countries. METHODS AND RESULTS: This randomized trial tested vitamin D 60,000 IU monthly in 5670 participants without vascular disease but at increased CV risk. The primary outcome was fracture. The secondary outcome was the composite of CV death, myocardial infarction stroke, cancer, fracture or fall. Death was a pre-specified outcome. Mean age was 63.9 years, and 3005 (53.0%) were female. 3034 (53.5%) participants resided in South Asia, 1904 (33.6%) in South East Asia, 480 (8.5%) in South America, and 252 (4.4%) in other regions. Mean follow-up was 4.6 years. A fracture occurred in 20 participants (0.2 per 100 person years) assigned to vitamin D, and 19 (0.1 per 100 person years) assigned to placebo (HR 1.06, 95% CI 0.57-1.99, p-value = 0.86). The secondary outcome occurred in 222 participants (1.8 per 100 person years) assigned to vitamin D, and 198 (1.6 per 100 person years) assigned to placebo (HR 1.13, 95% CI 0.93-1.37, p = 0.22). 172 (1.3 per 100 person years) participants assigned to vitamin D died, compared with 135 (1.0 per 100 person years) assigned to placebo (HR 1.29, 95% CI 1.03-1.61, p = 0.03). CONCLUSION: In a population predominantly from South Asia, South East Asia and South America, high-dose vitamin D did not reduce adverse skeletal or non-skeletal outcomes. Higher mortality was observed in the vitamin D group. REGISTRATION NUMBER: NCT01646437.

Cost implications of the use of basal insulin glargine in people with early dysglycemia: the ORIGIN trial.

AIMS: The cost implications of the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial were evaluated using a prespecified analysis plan. METHODS: Purchasing power parity-adjusted country-specific costs were applied to consumed healthcare resources by participants from each country. Subgroup analyses were conducted on subgroups based on baseline metabolic status and diabetes duration. RESULTS: The total undiscounted cost per participant in the insulin glargine arm was $13,491 ($13,080 to $14,254) versus $11,189 ($10,568 to $12,147) for standard care, an increase of $2303 ($1370 to $3235; p < 0.0001); the discounted increase was $2099 ($1276 to $2923; P < 0.0001). The greater number of mainly generic oral anti-diabetic agents in the standard group partially offset the higher cost of basal insulin glargine. As the trial progressed and the standard group required more anti-diabetic medications, the annual cost difference decreased, reaching $68 (-$160 to $295) in the last year. The subgroup whose baseline diabetes duration was ≥ 6 years achieved cost-savings during the trial. CONCLUSIONS: From a global perspective basal insulin glargine use in ORIGIN incurred greater costs than standard care using older generic drugs. Nevertheless, the cost difference fell with time such that the intervention was cost-neutral by the last year.