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Publications

Journal Article Ahead of print

PubMed: 42627334 DOI: 10.2337/dc26-1072

β-Cell Function and Diabetes Outcomes 1 Year After Stopping Oral Baricitinib Immunotherapy for Type 1 Diabetes.

Diabetes Care

Authors: Michelle So, Michaela Waibel, Jennifer J Couper, Fergus J Cameron, Richard J MacIsaac, Gabby Atlas, Alexandra Gorelik, Sara Vogrin, Sara Litwak, Laura Sanz-Villanueva, Prerak Trivedi, Jessica E Harbison, Candice Hall, Balasubramanian Krishnamurthy, Peter G Colman, Leonard C Harrison, Helen E Thomas, Thomas W H Kay, John M Wentworth

Affiliations

  • St Vincent's Institute of Medical Research, Fitzroy, Australia.
  • Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Parkville, Australia.
  • Womens and Children's Hospital, North Adelaide, Australia.
  • Adelaide University, Adelaide, Australia.
  • Department of Diabetes and Endocrinology, The Royal Children's Hospital, Parkville, Australia.
  • The Murdoch Children's Research Institute, Parkville, Australia.
  • Department of Paediatrics, University of Melbourne, Parkville, Australia.
  • Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, Fitzroy, Australia.
  • Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Fitzroy, Australia.
  • Australian Centre for Accelerating Diabetes Innovations, Melbourne Medical School, University of Melbourne, Parkville, Australia.
  • School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
  • Department of Medicine, University of Melbourne, Parkville, Australia.
  • School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
  • The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Department of Medical Biology, The University of Melbourne, Parkville, Australia.

Abstract

OBJECTIVE

The Baricitinib in New-Onset Type 1 Diabetes (BANDIT) trial showed that baricitinib treatment for 48 weeks preserved β-cell function and lowered insulin requirements and glucose in recent-onset type 1 diabetes. We aimed to determine the durability of these effects following treatment cessation.

RESEARCH DESIGN AND METHODS

The following posttreatment outcomes of the randomized, double-blind, placebo-controlled BANDIT trial were analyzed: C-peptide and glucagon responses to a mixed meal, HbA1c, continuous glucose monitoring (CGM) measures, CD8+ T-cell phenotype and function, and adverse events.

RESULTS

Of 91 randomized participants, 88 (58 baricitinib and 30 placebo) completed the week 96 follow-up. Mean ± SEM C-peptide was significantly greater in baricitinib-treated participants at week 72 (0.54 ± 0.05 vs. 0.38 ± 0.06 pmol/mL; P = 0.015) but not at week 96 (0.43 ± 0.05 vs. 0.35 ± 0.06 nmol/L; P = 0.336). No significant between-group differences in insulin dose, HbA1c, or CGM measures were observed during follow-up. Post hoc comparisons showed that when the study drug was ceased at week 48, baricitinib-treated adults (n = 28) experienced full preservation of β-cell function whereas C-peptide decreased relative to baseline by 0.09 pmol/mL in baricitinib-treated children (n = 32; P = 0.022). Baricitinib did not resolve paradoxical glucagon increase after a mixed meal. Decreased frequency and cytokine signaling of effector memory CD8+ T cells observed at week 48 resolved by week 96.

CONCLUSIONS

The benefits of oral baricitinib in type 1 diabetes wane over 48 weeks following treatment cessation. Durable benefit is likely to require continuous treatment.

MeSH

Diabetes Mellitus, Cells, Insulin, Withholding Treatment, Immunotherapy, Glucagon, Therapeutics, Meals, Diabetes Mellitus, Type 1