A phase 2 clinical trial has revealed that Eli Lilly's JAK inhibitor Olumiant (baricitinib) can preserve the function of insulin-producing pancreatic beta cells in patients with type 1 diabetes, potentially transforming treatment approaches for this autoimmune condition.
The investigator-led, placebo-controlled BANDIT trial found that Olumiant, already approved for rheumatoid arthritis, significantly slowed disease progression in recently diagnosed patients. Researchers from St Vincent's Institute of Medical Research in Melbourne, Australia, described the finding as "a huge step-change" in type 1 diabetes management.
"When type 1 diabetes is first diagnosed, there is a substantial number of insulin-producing cells still present," explained Professor Thomas Kay, lead author of the study published in the New England Journal of Medicine. "We wanted to see whether we could protect further destruction of these cells by the immune system. We showed that baricitinib is safe and effective at slowing the progression of type 1 diabetes in people who have been recently diagnosed."
Trial Design and Key Findings
The BANDIT trial enrolled 91 patients with type 1 diabetes diagnosed within the previous 100 days, aged between 10 and 30 years. Participants received either Olumiant at an oral dose of 4 mg daily or a matched placebo over 48 weeks while continuing their insulin therapy.
The primary outcome measure was C-peptide level in plasma—a marker for the body's ability to produce insulin—after a test meal. After 48 weeks, the Olumiant group demonstrated significantly improved C-peptide levels, with a median of 0.65 nmol per liter per minute compared to 0.43 nmol per liter per minute in the placebo group, indicating preserved beta cell function.
Importantly, patients taking Olumiant required significantly less insulin therapy and experienced decreased blood glucose fluctuations at 12 and 24 weeks compared to the placebo group.
Professor Helen Thomas, preclinical lead on the trial, expressed optimism: "We are very optimistic that this treatment will become clinically available. We believe it shows promise as a fundamental improvement in the ability to control type 1 diabetes."
The Burden of Type 1 Diabetes
Type 1 diabetes affects millions worldwide and requires lifelong insulin therapy. While insulin injections are life-saving, they can be hazardous if improperly dosed and place considerable burden on patients and caregivers. The disease occurs when the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas, leading to elevated blood glucose levels and potential complications.
Olumiant is thought to work by reducing the immune system's attack on beta cells with a single daily oral dose, potentially delaying the need for insulin injections or reducing required doses.
TYK2 Inhibition: Another Promising Approach
In parallel research, scientists at Indiana University School of Medicine and international collaborators have identified another potential therapeutic target for type 1 diabetes: the tyrosine kinase 2 (TYK2) protein.
Their laboratory studies using human cells and mouse models demonstrated that blocking inflammation signaling through TYK2 reduced harmful inflammation in the pancreas. This approach showed a dual benefit—protecting beta cells while simultaneously reducing immune system attacks.
"Our study showed that targeting TYK2 could be a powerful way to protect insulin-producing beta cells while calming inflammation in the immune system at the same time," said Dr. Carmella Evans-Molina, director of the Indiana Diabetes Research Center and co-author of the study published in eBioMedicine.
This finding is particularly promising because a TYK2 inhibitor is already FDA-approved for treating psoriasis, potentially accelerating the pathway to clinical trials for type 1 diabetes.
Genetic Evidence Supporting New Approaches
Previous genetic studies have shown that individuals with naturally lower TYK2 activity are less likely to develop type 1 diabetes, lending further support to this therapeutic approach.
"Our preclinical models suggest that the treatment might work in people as well," said Dr. Farooq Syed, lead author of the TYK2 study. "The next step is to initiate translational studies to evaluate the impact of TYK2 inhibition alone or in combination with other already approved drugs in individuals at-risk or with recent onset Type 1 diabetes."
Future Directions
Both research teams are optimistic about the clinical potential of their findings. The BANDIT trial results with Olumiant and the preclinical evidence for TYK2 inhibition represent significant advances in the quest to develop treatments that address the underlying autoimmune mechanisms of type 1 diabetes rather than simply managing symptoms.
These developments could eventually lead to combination therapies that target multiple aspects of the disease process, potentially preserving beta cell function for longer periods and reducing dependence on exogenous insulin.
As these promising approaches move toward clinical application, they offer hope for improved quality of life and better long-term outcomes for the millions of people living with type 1 diabetes worldwide.
