JAK inhibitor a new hope for new-onset T1D?

The 2-year outcomes from the phase II BANDIT* trial confirm the potential of the Janus kinase (JAK) inhibitor baricitinib for the treatment of new-onset type 1 diabetes (T1D).

“BANDIT is the first clinical trial to use a JAK inhibitor in T1D,” said Dr Michaela Waibel from the St Vincent’s Institute of Medical Research, Fitzroy, Australia, at EASD 2025. “JAK inhibitors block the cytokine-induced upregulation of HLA class 1 on the β cells themselves, thereby decreasing the HLA class 1 expression and ability to present antigen to cytotoxic CD8+ T cells.”

BANDIT enrolled 91 individuals (mean age 18.6 years, 58 percent men) who had been diagnosed with T1D in the past 100 days, had residual C-peptide, and had evidence of islet autoantibody positivity. They were randomized 2:1 to baricitinib 4 mg or placebo orally QD for 48 weeks. [EASD 2025, abstract 220]

At week 48, C-peptide levels were 0.65 and 0.43 in the respective baricitinib and placebo arms (p=0.001). After treatment cessation, these levels dropped to 0.49 and 0.36, respectively (p=0.015) at week 72, and further to 0.37 and 0.26 at week 96 (p=0.336).

The decline in C-peptide level with baricitinib during the off-drug follow-up period was associated with an increased insulin dose. However, no significant between-group differences were observed at the follow-up assessment time points after treatment ceased.

HbA_1c levels were also not significantly different at any time point during and after treatment, but continuous glucose monitoring measures, such as coefficient of variation and time in range, improved with baricitinib during the treatment period.

Although the study was not powered to detect differences in the age subgroup analysis, some trends worth noting are the slightly better effect on C-peptide preservation among adults (18–30 years) and the HbA_1c reduction in adults, which was not observed in the overall cohort, Waibel pointed out.

In summary, these results show that daily baricitinib is effective in preserving C-peptide during treatment, which is tied to reduced blood glucose variations and lower insulin requirements, Waibel said.

She added that baricitinib is well-tolerated and safe, and the effect wanes once the treatment is stopped. The treatment was effective in both adolescents and adults, and no baseline predictors of treatment response were identified. “We think baricitinib will play an important role in protecting endogenous insulin production in T1D patients.”

An exciting step forward

The current results support the initial BANDIT findings showing that daily baricitinib over 48 weeks appears to preserve β-cell function as estimated by the mixed-meal-stimulated mean C-peptide level. [N Engl J Med 2023;389:2140-2150]

“Among the agents reported as promising for the preservation of β-cell function in T1D, baricitinib stands out because it is administered orally, is well-tolerated … and is clearly efficacious,” Waibel noted in the press release.

“This is a really exciting step forward. For the first time, we have an oral disease-modifying treatment that can intervene early enough to allow people with T1D to be significantly less dependent on insulin treatment and provide time free from the demands of the disease’s daily management, and which could also lower rates of long-term complications,” Waibel said.

“If we can identify people at high risk of developing T1D with genetic tests and blood markers, they could be offered treatment even earlier to prevent the disease from taking hold in the first place,” Waibel added.

Larger phase III trials in individuals with recently diagnosed T1D and in the earlier stages of the disease are anticipated. “If these trials are successful, the drug could be approved for T1D treatment within 5 years,” she said.

If approved for T1D, this would expand the treatment scope of baricitinib, which is already approved for a range of indications, including rheumatoid arthritis, COVID-19, and alopecia areata. [https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/207924s007lbl.pdf, accessed October 1, 2025]