A trial comparing baricitinib against placebo in people with new-onset type 1 diabetes suggests use could contribute to the preservation of β-cell function.
Baricitinib (Olumiant), an agent used in the treatment of rheumatoid arthritis, could prove useful for delaying the progression of type 1 diabetes, according to data from a randomized, controlled trial of 91 patients.
Funded by JDRF International, the trial, which compared baricitinib against placebo for preserving β-cell function in type 1 diabetes, concluded daily treatment with baricitinib over 48 weeks reduced need for insulin and appeared to preserve β-cell function among these patients.1
“It is tremendously exciting for us to be the first group anywhere in the world to test the efficacy of baricitinib as a potential type 1 diabetes treatment,” said principal investigator Thomas Kay, MBBS, PhD, director of and head of the Tom Mandel Islet Transplant Program at St Vincent's Institute in Melbourne.2 “Up until now, people with type 1 diabetes have been reliant on insulin delivered via injection or infusion pump. Our trial showed that, if started early enough after diagnosis, and while the participants remained on the medication, their production of insulin was maintained.”
In the 100 years after the discovery of insulin, the management of type 1 diabetes underwent relatively little significant changes. Although technology and management practices had improved, it was not until late 2022 when the FDA approved teplizumab (Tzield) as the first agent to delay the onset of type 1 diabetes.3 The year 2023 has brought forth even further progress in this arena, with the FDA approving donislecel (Lantidra) for treatment of adults with type 1 diabetes and new data from abatacept purporting benefit for preservation of β-cell function in type 1 diabetes.4,5
A Janus kinase (JAK) inhibitor from Eli Lilly and Company, baricitinib received approval from the FDA for the treatment of moderately-to-severely active rheumatoid arthritis in 2018. In the half-decade since its initial approval, the agent went on to receive approval and as the first systemic medicine to receive approval for adults with severe alopecia areata.6 A class known for its ability to block cytokine signaling and with a growing reputation for its effects on several autoimmune diseases, preclinical data from animal models suggest use of JAK inhibitors might have an effect on β-cell function in type 1 diabetes.1
Known as the Baricitinib in Newly Diagnosed Type 1 Diabetes (BANDIT) trial, the phase 2, double-blind, randomized, placebo-controlled study conducted at 4 trial sites in Australia. With enrollment occurring between November 2020 and February 2022, investigators identified 106 patients who underwent screening. Of these, 91 underwent randomization, with 60 randomized to baricitinib and 31 randomized to placebo.1
To be eligible for inclusion in the trial, patients need to be between 10 and 30 years of age, have a diagnosis of type 1 diabetes within 100 days before starting baricitinib or placebo, the presence of at least one islet autoantibody, and either a random C-peptide level of more than 0.3 nmol/Lor a C-peptide level of more than 0.2 nmol/L during a 2-hour mixed-meal tolerance test.1
Per trial protocol, participants were randomized in a 2:1 ratio to once-daily 4 mg baricitinib or matching placebo for 48 weeks. The primary outcome of interest for the trial was the mean C-peptide level during a 2-hour mixed-meal tolerance test at week 48, which was assessed using area under the concentration–time curve. The trial also included change from baseline in the glycated hemoglobin level, the daily insulin dose, and measures of glycemia as secondary outcomes of interest.1
Results of the trial suggested the median of the mixed-meal–stimulated mean C-peptide level at week 48 was 0.65 nmol/L per minute (interquartile range [IQR], 0.31 to 0.82) in the baricitinib group and 0.43 nmol/L per minute (IQR, 0.13 to 0.63) in the placebo group (P=.001). Investigators pointed out these figures represent decreases of 4.2% (95% Confidence Interval [CI], −6.3 to 14.9)and 29.9% (95% CI, 17.1 to 42.7) relative to baseline in the baricitinib and placebo groups, respectively.1
At week 48, the mean daily insulin dose was 0.41 U per kilogram of body weight per day (95% CI, 0.35 to 0.48) in the baricitinib group and 0.52 U per kilogram per day (95% CI, 0.44 to 0.60) in the placebo group. Investigators highlighted mean daily insulin dose in the baricitinib group at weeks 12 and 24 was less than that at baseline. In contrast, the mean daily insulin dose in the placebo group at week 24 was greater than at baseline. Investigators also pointed out similar between-group differences were observed for basal and mealtime insulin doses.1
Analysis of glycemic measures revealed the mean HbA1c was 7.0% (95% CI, 6.6 to 7.4)in the baricitinib group and 7.5% (95% CI, 6.9 to 8.0) in the placebo group at week 48. However, investigators noted the mean coefficient of variation of the glucose level at 48 weeks was 29.6% (95% CI, 27.8 to 31.3) in the baricitinib group and 33.8% (95% CI, 31.5 to 36.2) in the placebo group.1
Analysis of adverse events indicated the frequency and severity of adverse events were similar among the trial groups. A total of 7 serious adverse events occurred in the trial, but none were attributed to baricitinib or placebo therapy.1
Although the trial’s primary funder was JDRF and Eli Lilly and Company provided baricitinib and identical placebo tablets for use, investigators underlined neither was involved in the conduct of the trial, interpretation of data, or decision to submit the manuscript for publication.1
“We are very optimistic that this treatment will become clinically available. This would be a huge step-change in how type 1 diabetes is managed and we believe it shows promise as a fundamental improvement in the ability to control type 1 diabetes,” said study investigator Helen Thomas, PhD, head of the Immunology and Diabetes Unit at St Vincent's Institute in Melbourne.2