Diabetes Dialogue: Baricitinib & the Potential Disease-Modifying Therapies in Type 1 Diabetes

For a century, since the introduction of insulin, the diabetes community yearned for the advent of a disease-modifying therapy for type 1 diabetes. Practitioners and patients had their wish granted in 2022 with the US Food and Drug Administration’s approval of teplizumab (Tzield) for delaying the progression of type 1 diabetes. In 2023, the community was offered a glimpse into what the future might hold for type 1 diabetes management.

In December 2023, the results of the BANDIT trial published in the New England Journal of Medicine suggested use of baricitinib (Olumiant) was associated with a reduction in need for insulin and preservation of β-cell function among adults with type 1 diabetes. With a population of 91 patients randomized 2:1 to baricitinib or placebo for 48 weeks, results of the trial indicated use of the JAK inhibitor from Eli Lilly and Company was associated with a reduced need for daily insulin relative to placebo and greater mixed-meal–stimulated mean C-peptide level, which was used to estimate impact on β-cell function.¹

This New England Journal of Medicine study is not the first piece of data purporting benefit for patients with type 1 diabetes in the form of beta cell preservation or eliminating the need for insulin. During 2023, the community welcomed new data from teplizumab (Tzield) in the PROTECT trial, results of a phase 1/2 trial examining a stem cell-derived therapy from Vertex Therapeutics, and a case series on semaglutide use in newly diagnosed type 1 diabetes.^2,3,4

In PROTECT, which was a phase 3, randomized, placebo-controlled trial, patients with stage 3 type 1 diabetes were randomized them in a 2:1 ratio to teplizumab or matching placebo for 2, 12-day courses. The primary outcome of interest for the trial was change from baseline in β-cell function, as measured by stimulated C-peptide levels at week 78.²

Results of the PROTECT trial suggested was associated with a significant slowing of the decline of C-peptide levels relative to placebo therapy in people with stage 3 autoimmune type 1 diabetes, but further analysis indicated numerical trends for key secondary endpoints, such as time in range, HbA1c, and total insulin doses, failed to reach statistical significance.²

At the 2023 Annual Meeting of the European Association for the Study of Diabetes, Trevor Reichman, MD, a professor in the department of surgery at the University of Toronto, presented data from parts A and B of a phase 1/2 trial examining use of VX-880 in people with type 1 diabetes. Data from this trial suggest all participants dosed with VX-880 and 90 days of follow-up demonstrated engraftment of islet cells, produced endogenous insulin, and had improved glycemic control while reducing or eliminating insulin use.³

In September 2023, a case series published in the New England Journal of Medicine detailed benefit from use of semagltuide 1.0 mg in patients with newly diagnosed type 1 diabetes. A case series of 10 patients, data in the report indicates use of semaglutide eliminated the need for mealtime insulin doses among the entire study cohort and allowed 70% to eliminate basal insulin use within 6 months, with the mean HbA1c decreasing from 11.7% at baseline to 5.9% at 6 months and 5.7% at 12 months.⁴

In this episode of Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives, hosts hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, discuss the study on baricitinib, how these results compare to other data in this arena, and what all of these studies mean for future of type 1 diabetes management.

Relevant disclosures for Dr. Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Dr. Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.

References:

1. Waibel M, Wentworth JM, So M, et al. Baricitinib and β-Cell Function in Patients with New-Onset Type 1 Diabetes. N Engl J Med. 2023;389(23):2140-2150. doi:10.1056/NEJMoa2306691
2. Ramos EL, Dayan CM, Chatenoud L, et al. Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes. N Engl J Med. 2023;389(23):2151-2161. doi:10.1056/NEJMoa2308743
3. Iapoce C. Stem cell-derived therapy improves glucose control in type 1 diabetes. HCP Live. October 4, 2023. Accessed January 2, 2024. https://www.hcplive.com/view/stem-cell-derived-therapy-improves-glucose-control-type-1-diabetes.
4. Dandona P, Chaudhuri A, Ghanim H. Semaglutide in Early Type 1 Diabetes. N Engl J Med. 2023;389(10):958-959. doi:10.1056/NEJMc2302677