Oral drug baricitinib/alemin shows promise in slowing progression of early-stage type 1 diabetes

The BANDIT trial reports that a daily pill of baricitinib, commonly used for rheumatoid arthritis and hair loss, can safely maintain the body's own insulin production and slow the progression of the disease in people recently diagnosed with type 1 diabetes (T1D).

Follow-up of the blindedBANDIT trial showed that once treatment with baricitinib was stopped, participants' diabetes worsened and they produced less insulin and had unstable blood sugar levels that were not significantly different from those in the placebo group. These latest data support our previous clinical trial data showing that treatment effects are lost when baricitinib is discontinued and justify further trials to determine whether treatment effects can be sustained over many years of treatment and whether treating early-stage disease can prevent or delay clinical diagnosis.

T1D is caused by the immune system mistakenly attacking insulin-secreting cells in the pancreas. Over time, this results in the need for lifelong insulin injections to control blood sugar levels.

Baricitinib is a Janus kinase (JAK) inhibitor that works by blocking signals in the body that cause the immune system to become overactive and helps protect remaining insulin-secreting cells in people newly diagnosed with T1D, thereby slowing the progression of full symptoms. It has been used to treat several autoimmune diseases, including rheumatoid arthritis, ulcerative colitis, and alopecia.

The BANDIT trial enrolled 91 people aged 10 to 30 who had been diagnosed with T1D in the past 100 days. Participants took either baricitinib (4 mg) or placebo once daily for 48 weeks.

At the beginning of the trial and at weeks 12, 24 and 48, the researchers measured participants' C-peptide levels, a marker of insulin secretion, to see how much insulin the participants themselves were producing. They also used continuous glucose monitoring and HbA1c, a marker of long-term blood sugar levels, to assess the need for insulin injections and how well blood sugar levels were being managed.

Study results show that taking baricitinib daily for 48 weeks can preserve insulin-secreting beta cell function, reduce blood sugar fluctuations, and reduce the need for insulin in patients with newly diagnosed T1D. The researchers also found that baricitinibIt is safe and the drug has no side effects. In this study, results from the off-treatment follow-up period were reported and were assessed at weeks 72 and 96.

At 48 weeks, C-peptide levels were 0.65 in the baricitinib group and 0.43 in the placebo group. After stopping treatment, C-peptide levels dropped to 0.49 in the baricitinib group at 72 weeks and 0.36 in the placebo group, and dropped to 0.37 and 0.26 respectively at 96 weeks, indicating reduced insulin secretion. After cessation of baricitinib insulin secretionThe decline in β-cell function led to the need for more insulin treatment, and there was no significant difference in insulin requirements between the two groups at weeks 72 and 96.

Discontinuation of baricitinib also resulted in worsening of glycemic control, with the differences in time spent within the safe blood sugar range and blood sugar fluctuations between the two groups no longer being statistically significant at weeks 72 and 96 during the first 48 weeks. Further analysis could not identify any characteristics that predicted treatment response at the start of the trial, including age, specific immune system genes called human leukocyte antigens (HLA), body mass index (BMI) or the number of autoantibodies. Additionally, medication compliance (taking at least 80% of study medication) did not distinguish responders from non-responders. Overall, about two-thirds of participants taking baricitinib met response criteria.

Of note, no additional safety concerns were raised during follow-up.

Reference materials:https://go.drugbank.com/drugs/DB11817