Two studies and an editorial explore the use of Janus kinase (JAK) inhibitors for preserving pancreatic β-cell function and preventing disease progression in type 1 diabetes. A phase 2 trial tests the effects of baricitinib in patients diagnosed with type 1 diabetes during the prior 100 days, while a phase 3 trial assesses the effects of teplizumab in patients who are newly diagnosed with type 1 diabetes.
Baricitinib 4 mg once daily or placebo was administered to 91 patients in a trial with a primary outcome of the mean C-peptide level during a 2-hour mixed-meal tolerance test after 48 weeks: “The median of the mixed-meal–stimulated mean C-peptide level at week 48 was 0.65 nmol per liter per minute (interquartile range, 0.31 to 0.82) in the baricitinib group and 0.43 nmol per liter per minute (interquartile range, 0.13 to 0.63) in the placebo group (P = 0.001). The mean daily insulin dose at 48 weeks was 0.41 U per kilogram of body weight per day (95% confidence interval [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. The levels of glycated hemoglobin were similar in the two trial groups. However, the mean coefficient of variation of the glucose level at 48 weeks, as measured by continuous glucose monitoring, 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. The frequency and severity of adverse events were similar in the two trial groups, and no serious adverse events were attributed to baricitinib or placebo.”
The change from baseline in β-cell function, as measured by stimulated C-peptide levels at week 78, was examined in the teplizumab trial: “Patients treated with teplizumab (217 patients) had significantly higher stimulated C-peptide levels than patients receiving placebo (111 patients) at week 78 (least-squares mean difference, 0.13 pmol per milliliter; 95% confidence interval [CI], 0.09 to 0.17; P <0.001), and 94.9% (95% CI, 89.5 to 97.6) of patients treated with teplizumab maintained a clinically meaningful peak C-peptide level of 0.2 pmol per milliliter or greater, as compared with 79.2% (95% CI, 67.7 to 87.4) of those receiving placebo. The groups did not differ significantly with regard to the key secondary end points. Adverse events occurred primarily in association with administration of teplizumab or placebo and included headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome.”
Editorial: “Taken together, these trials indicate that, finally, we have promising treatments that may soon be offered to patients with type 1 diabetes at the onset of their disease, and more studies are on their way,” writes an editorialist. “With sufficient health care resources, these treatments will be pragmatically feasible. Will clinicians, patients, or parents of children with diabetes see these treatments as justified? For patients with cancer, the alternative to treatment is death, and for some patients with certain autoimmune diseases, treatment is the only way to decrease suffering. 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. Although modern devices are expensive and not an option for all patients, 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. In addition, 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.”