American Diabetes Association
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Hydroxychloroquine in Stage 1 Type 1 Diabetes

Version 2 2023-10-12, 19:30
Version 1 2023-09-14, 19:36
posted on 2023-10-12, 19:30 authored by Ingrid Libman, Polly J. Bingley, Dorothy Becker, Jane H. Buckner, Linda A DiMeglio, Stephen E. Gitelman, Carla Greenbaum, Michael J. Haller, Heba M. Ismail, Jeffrey Krischer, Wayne V Moore, Antoinette M. Moran, Andrew B. Muir, Vana Raman, Andrea K Steck, Frederico GS Toledo, John WentworthJohn Wentworth, Diane K. Wherrett, Perrin C White, Lu You, Kevan C. Herold

Objective: Innate immune responses may be involved in the earliest phases of type 1 diabetes.

Research Design and Methods: To test whether blocking innate immune cells modulated progression of the disease we randomized 273 individuals with stage 1 type 1 diabetes to treatment with hydroxychloroquine (n=183, 5 mg/kg/d to a maximum of 400 mg) or placebo (n=90) and assessed whether hydroxychloroquine treatment delayed or prevented progression to stage 2 T1D (i.e. two or more islet autoantibodies with abnormal glucose tolerance).

Results: After median follow up of 23.3 months, the trial was stopped prematurely by the Data Safety Monitoring Board because of futility. There were no safety concerns in the hydroxychloroquine arm, including in annual ophthalmologic exams. Preplanned secondary analyses showed a transient decrease in the glucose average area under the curve to oral glucose in the hydroxychloroquine-treated arm at month 6 and a reduced titer of anti-GAD and anti-insulin autoantibodies and acquisition of positive autoantibodies in the hydroxychloroquine arm (p=0.032).

Conclusions: We conclude that hydroxychloroquine does not delay the progression to stage 2 type 1 diabetes in individuals with stage 1 disease. Drug treatment reduces the acquisition of additional autoantibodies and the titers of autoantibodies to GAD and insulin.


The Type 1 Diabetes TrialNet Study Group is a clinical trials network currently funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), through the cooperative agreements U01 DK061042, U01 DK061058, U01 DK084565, U01 DK085453, U01 DK085461, UC4 DK085466, U01 DK085476, U01 DK085504, U01 DK085509, U01 DK103282, U01 DK106984, UC4 DK106993, U01 DK106994, U01 DK107013, U01 DK107014. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


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