The oral Janus kinase inhibitor baricitinib (Olumiant) preserved beta-cell function in people with new-onset type 1 diabetes over 48 weeks, new phase 2 data show. 

But, as with the intravenously administered monoclonal antibody teplizumab (Tzield), there were no significant improvements in A1c and all study participants continued to require exogenous insulin. Both drugs are currently on the US market — baricitinib for rheumatoid arthritis, alopecia areata, and COVID-19 and teplizumab for delaying the onset of type 1 diabetes in those with preclinical (stage 2) disease. 

A randomized, placebo-controlled trial examined baricitinib vs placebo in 91 people with type 1 diabetes onset during the previous 100 days. Published in The New England Journal of Medicine (NEJM) on December 7, 2023, the research was performed by Michaela Waibel, PhD, of St. Vincent’s Institute of Medical Research, Melbourne, Australia, and colleagues. 

A phase 3 teplizumab trial, of two 12-day courses or placebo given to 328 young people with new-onset type 1 diabetes, was also published in the December 7, 2023, issue of NEJM. That study appeared online on October 18, 2023, and was reported by Medscape Medical News. 

In an editorial in the same issue, Johnny Ludvigsson, MD, PhD, of Crown Princess Victoria Children’s Hospital and the Division of Pediatrics, Linköping University, Linköping, Sweden, writes that the two trials together “indicate that, finally, we have promising treatments that may soon be offered to patients with type 1 diabetes at the onset of their disease. With sufficient health care resources, these treatments will be pragmatically feasible.”

Ludvigsson also points out that even though thus far, these interventions aren’t cures and patients must still administer exogenous insulin, preserved residual beta-cell secretion of even small amounts of insulin can help minimize glucose fluctuations and thereby potentially reduce the risk for long-term complications. 

However, he questions whether clinicians, patients, or their parents will see these treatments as justified because other options for improving glycemia are available. “For patients with type 1 diabetes, immunologic interventions to preserve β-cell function arrive in parallel with glucose sensors, smart insulin pumps, and even closed-loop systems…immunologic interventions can be expected to be accepted and successful if clinicians are able to explain the great value for the patient of residual insulin secretion.”

At the same time, he notes, “the interventions to preserve β-cell function must be proved to be safe and to not cause serious adverse events in both the short and the long term. If patients with type 1 diabetes, who already have a chance for a good-quality, long life with modern conventional treatment, are to start receiving such therapy, it should not add to their already heavy burden.”

In the baricitinib study, 60 patients were randomly assigned to receive the drug at 4 mg/da and 31 to receive matched oral placebo. The primary outcome, mean C-peptide level determined by area under the curve during a 2-hour mixed meal tolerance test at week 48, was 0.65 nmol/L/min with baricitinib vs 0.43 nmol/L/min with placebo — a significant difference (P = .001). 

There were no significant differences in daily insulin dose or A1c, but the mean coefficient of variation in glucose levels, as measured by continuous glucose monitoring, was lower with baricitinib: 29.6% vs 33.8% with placebo. 

Waibel and colleagues write, “We speculate that the initiation of baricitinib earlier, when the C-peptide level is higher, either immediately after the diagnosis of symptomatic clinical type 1 diabetes or during presymptomatic stage 2 or stage 3A disease identified through the screening of relatives of patients with type 1 diabetes or through the screening of the general population, may be more effective in decreasing the need for injected insulin.”

Adverse event frequency and severity didn’t differ between the two groups, and there were no severe treatment-associated adverse events.

In the teplizumab trial, participants randomly assigned to receive teplizumab had significantly higher stimulated C-peptide levels than did those assigned to placebo at week 78, with a difference of 0.13 pmol/mL (P <  .001).

There were no significant differences in other endpoints, including insulin doses required to meet glycemic goals, A1c, time in range, or significant hypoglycemic events. 

And with teplizumab, despite premedication in anticipation of discomfort and adverse events, some patients still experienced headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome. Two patients had severe cytokine release syndrome that resolved within a week but led to treatment discontinuation. 

Ludvigsson concludes, “As clinicians, we need to learn how best to combine therapies to preserve β cells and to control type 1 diabetes. Furthermore, we must learn to which patient a certain immunologic therapy should be given, and for how long. With increasing knowledge from treatment trials involving patients with early stage 3 (clinical) diabetes, we should learn whether such therapy can contribute to a cure and possibly prevent clinical disease if used in earlier stages of type 1 diabetes.”