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Once-daily, high-dose oral insulin can delay the onset of type 1 diabetes mellitus (T1DM) in children who are genetically at risk of the disease, a study published in The Lancet has revealed.
In the study, published on 11 November 2025, researchers genetically screened newborns from seven obstetric and paediatric clinics in Germany, Poland, Sweden, Belgium and the UK to identify those with a greater than 10% risk of developing islet auto-immunity.
In patients with islet auto-immunity, it is thought that the immune system attacks and destroys beta cells that produce insulin, which results in T1DM.
Of those screened, 1,050 infants were assigned 1:1 to receive either oral insulin or placebo for three years. Those patients who received oral insulin were given a once-daily dose of 7.5mg for two months, which increased to 22.5mg for two months and then 67.5mg until the age of three years.
The primary outcome was the development of two or more islet auto-antibodies or diabetes, assessed throughout follow-up until a maximum age of 6.5 years. A secondary outcome was the development of dysglycaemia or diabetes.
Samples of islet autoantibodies were collected at baseline at 2, 4 and 8 months after randomisation, at the age of 18 months and every 6 months thereafter.
The researchers found that the primary outcome developed in 52 participants (10%) from the insulin group and 46 participants (9%) in the placebo group.
The five-year probability of islet autoantibody development was 13.4% in the insulin group and 14.9% in the placebo group, which showed no significant difference, the researchers noted. However, they revealed that progression to T1DM was around 50% slower in the insulin group compared with placebo.
The effect of the treatment also varied depending on the child’s genotype, with those with the INS AA genotype showing greater benefit, according to the study results.
Lead researcher Anette-Gabriele Ziegler, chair of diabetes and gestational diabetes at the TUM University Hospital and the director of the Helmholtz Munich Institute of Diabetes Research, said: “The POInT study will change how we approach antigen-based therapies in T1DM. While the oral insulin therapy could not prevent the development of islet autoantibodies as we had hoped, the trial data suggest that this therapy may positively influence the course of the disease.
“First, we saw a delay in the progression to clinical disease in those who had received oral insulin, which is already a positive message. Second, a striking finding was how the treatment effect varied depending upon the genetics of the child. In particular, among children with T1DM risk variants of the insulin gene, a delay in the onset of T1DM appears possible, opening the door to targeted, personalised prevention of T1DM.”
Nabil Boulos, specialist pharmacist, paediatric endocrinology and diabetes at Southampton Children’s Hospital, commented: “The future management of T1DM is expected to shift from treatment to primary prevention over the coming years, and an increasing number of studies is investigating potential agents that can shift the course of disease progression.
“Even when prevention is not attainable, a delay in progression to T1DM by several years can have benefits to the child and family, such as reducing the incidence of diabetic ketoacidosis on diagnosis and allowing more planning time for patient and carer education. These therapies can make for a less stressful and smoother transition to the diagnosis of a life-long condition.”
He added: “The POInT study showed that giving oral insulin to infants can delay progression to T1DM. The remarkable aspect of this study is that it showed a different response based on the specific genotype, making it the first trial with a promise of personalised pharmacogenomic medicine for T1DM.
“As these novel therapies expand, the role of pharmacists should equally broaden to support clinicians with choices and initiating individualised therapies based on a person’s specific genetic and immune background.”
In August 2025, the Medicines and Healthcare products Regulatory Agency approved the UK’s first immunotherapy, teplizumab (Tzield; Sanofi), for delaying the progression of T1DM in patients aged eight years and older.
