Baricitinib may preserve beta-cell function in early stages of type 1 diabetes
An editorial noted that increasing knowledge developed from trials of patients with early type 1 diabetes could eventually enable treatment to prevent clinical disease.
Baricitinib daily for 48 weeks appeared to preserve beta-cell function in patients with recent onset of type 1 diabetes, a study found.
Researchers conducted a phase 2, double-blind trial in which patients with type 1 diabetes diagnosed within the past 100 days were randomized to baricitinib, 4 mg per day, or placebo for 48 weeks. The primary outcome was mean C-peptide level during a two-hour mixed-meal tolerance test at week 48. Secondary outcomes included change from baseline in HbA1c level, daily insulin dose, and measures of glycemic control assessed by continuous glucose monitoring. Results were published Dec. 7 by The New England Journal of Medicine.
Ninety-one patients were assigned to receive baricitinib (n=60) or placebo (n=31). The median of the mixed-meal-stimulated mean C-peptide level at week 48 was 0.65 nmol/L per minute (interquartile range, 0.31 to 0.82) in the baricitinib group compared to 0.43 nmol/L 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/kg of body weight per day (95% CI, 0.35 to 0.48) in the baricitinib group and 0.52 U/kg per day (95% CI, 0.44 to 0.60) in the placebo group.
HbA1c levels were similar in the two groups, although 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 as measured by continuous glucose monitoring. Frequency and severity of adverse events were similar in the two trial groups, with no serious adverse events attributed to the drug or to placebo.
The researchers wrote that starting 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, may be more effective in decreasing the need for injected insulin.
An editorial noted that diabetes care has focused almost completely on the consequences of diabetes, such as blood glucose control, with very limited attention to pancreatic beta cells, comparing this to treating thyroid disease without measuring thyroid hormones. Immunologic interventions to preserve beta-cell function arrived in parallel with glucose sensors, smart insulin pumps, and closed-loop systems, the editorial noted.
“As clinicians, we need to learn how best to combine therapies to preserve β cells and to control type 1 diabetes,” the editorial concluded. “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.”
ACP Diabetes Monthly reported on other new therapeutics to prevent beta-cell loss in last month's issue.