• Michaela Waibel, John M Wentworth, Michelle So, Jennifer J Couper, Fergus J Cameron, Richard J MacIsaac, Gabby Atlas, Alexandra Gorelik, Sara Litwak, Laura Sanz-Villanueva, Prerak Trivedi, Simi Ahmed, Francis J Martin, Madeleine E Doyle, Jessica E Harbison, Candice Hall, Balasubramanian Krishnamurthy, Peter G Colman, Leonard C Harrison, Helen E Thomas, KayThomas W HTWHFrom St. Vincent's Institute of Medical Research (M.W., M.S., S.L., L.S.-V., P.T., M.E.D., C.H., B.K., H.E.T., T.W.H.K.), St. Vincent's Hospital Melbourne (R.J.M., B.K., T.W.H.K.), and the Department of Medicine at St. Vincent's Hospital, , and BANDIT Study Group.
• From St. Vincent's Institute of Medical Research (M.W., M.S., S.L., L.S.-V., P.T., M.E.D., C.H., B.K., H.E.T., T.W.H.K.), St. Vincent's Hospital Melbourne (R.J.M., B.K., T.W.H.K.), and the Department of Medicine at St. Vincent's Hospital, University of Melbourne (R.J.M., L.S.-V., M.E.D., B.K., H.E.T., T.W.H.K.), Fitzroy, the Walter and Eliza Hall Institute of Medical Research (J.M.W., P.G.C., L.C.H.), the Departments of Medical Biology (J.M.W., L.C.H.) and Medicine (A.G.), University of Melbourne, the Royal Melbourne Hospital (J.M.W., M.S., C.H., P.G.C., L.C.H.), the Royal Children's Hospital (F.J.C., G.A.), and the Murdoch Children's Research Institute (F.J.C.), Parkville, and the School of Public Health and Preventive Medicine, Monash University, Melbourne (A.G.), VIC, and Women's and Children's Hospital (J.J.C., J.E.H.) and the University of Adelaide (J.J.C.), Adelaide, SA - all in Australia; the New York Stem Cell Foundation, New York (S.A.); and Macromoltek, Austin, TX (F.J.M.).
• N. Engl. J. Med. 2023 Dec 7; 389 (23): 214021502140-2150.

BackgroundJanus kinase (JAK) inhibitors, including baricitinib, block cytokine signaling and are effective disease-modifying treatments for several autoimmune diseases. Whether baricitinib preserves β-cell function in type 1 diabetes is unclear.MethodsIn this phase 2, double-blind, randomized, placebo-controlled trial, we assigned patients with type 1 diabetes diagnosed during the previous 100 days to receive baricitinib (4 mg once per day) or matched placebo orally for 48 weeks. The primary outcome was the mean C-peptide level, determined from the area under the concentration-time curve, during a 2-hour mixed-meal tolerance test at week 48. Secondary outcomes included the change from baseline in the glycated hemoglobin level, the daily insulin dose, and measures of glycemic control assessed with the use of continuous glucose monitoring.ResultsA total of 91 patients received baricitinib (60 patients) or placebo (31 patients). 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.ConclusionsIn patients with type 1 diabetes of recent onset, daily treatment with baricitinib over 48 weeks appeared to preserve β-cell function as estimated by the mixed-meal-stimulated mean C-peptide level. (Funded by JDRF International and others; BANDIT Australian New Zealand Clinical Trials Registry number, ACTRN12620000239965.).Copyright © 2023 Massachusetts Medical Society.

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