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Hydroxychloroquine for stage-1 T1D prevention

Generic

A cheap, oral immune-modulating drug tested by TrialNet in people with stage-1 type 1 diabetes (multiple autoantibodies but normal glucose). The TN-22 randomized trial was stopped early for futility: hydroxychloroquine did not delay progression to abnormal glucose tolerance or diabetes.

DiscontinuedModerate evidenceimmunotherapyoralnegative-trialstage-1

The scorecard

Delay of onset5

TN-22 showed no meaningful delay in progression to abnormal glucose tolerance or diabetes (HR 0.95, 95% CI 0.56-1.61; 34 of 183 on hydroxychloroquine vs 17 of 90 on placebo).[1]

Durability5

There was no clinical prevention effect to sustain, despite some immune marker changes.[1]

Safety75

The TrialNet study reported no retinal toxicity on annual eye exams and overall reassuring safety, but prevention use would still treat otherwise well people.[1]

Stage breadth25

Tested only in stage-1, multiple-autoantibody-positive people with normal glucose tolerance; not shown useful in later stages.[2]

Access & cost20

The pill is inexpensive and widely available for other diseases, but it is not approved or clinically useful for T1D prevention after the negative TrialNet result.[1]

Editor’s take

This belongs in the database precisely because it failed. Negative prevention trials are part of the map: hydroxychloroquine changed autoantibody signals but not the disease timeline, so it should not be treated as an active prevention option.

The full picture

Hydroxychloroquine is an old, inexpensive oral drug used in malaria and autoimmune diseases such as lupus. TrialNet tested it because it can dampen immune activation and might have been a practical early-stage prevention therapy if it slowed the autoimmune attack behind type 1 diabetes.1

What TN-22 tested

TN-22 enrolled people aged 3 and older with stage-1 T1D: two or more islet autoantibodies on repeated testing, but normal glucose tolerance. Participants were randomized 2:1 to hydroxychloroquine (5 mg/kg/day, maximum 400 mg/day) or placebo and followed with oral glucose tolerance testing every 6 months.12

Result

The trial was stopped early for futility after a median follow-up of about 23 months. Hydroxychloroquine did not delay progression to abnormal glucose tolerance or diabetes, with a hazard ratio of 0.95 (95% CI 0.56-1.61). Thirty-four drug-treated and 17 placebo participants progressed.1

The drug was reassuringly safe in the trial, including no retinal toxicity on annual eye exams. It also changed some immune markers — anti-GAD and anti-insulin autoantibody titers were lower, and fewer new autoantibodies appeared — but those signals did not translate into clinical benefit.1

What it means

Hydroxychloroquine is not a T1D prevention therapy. Its value here is as a clear negative result: broad, gentle immune modulation at stage 1 was not enough to delay abnormal glucose tolerance or clinical diabetes. That helps narrow the prevention pipeline toward more targeted immune approaches and better stage-specific trial design.

References

  1. Libman I, Bingley PJ, Becker D, et al.; Type 1 Diabetes TrialNet Study Group. Hydroxychloroquine in Stage 1 Type 1 Diabetes. Diabetes Care (2023);46(11):2035-2043. https://doi.org/10.2337/dc23-1096 ↩ ↩2 ↩3 ↩4

  2. National Institute of Diabetes and Digestive and Kidney Diseases. Hydroxychloroquine in Individuals At-risk for Type 1 Diabetes Mellitus (TN-22), NCT03428945. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT03428945 ↩

Sources

  1. [1]Hydroxychloroquine in Stage 1 Type 1 Diabetes · peer-reviewed · 2023-09-06 — Libman et al., Diabetes Care 2023;46:2035-2043. Trial stopped early for futility; HR 0.95 for progression to abnormal glucose tolerance or diabetes.
  2. [2]Hydroxychloroquine in Individuals At-risk for Type 1 Diabetes Mellitus · registry — TrialNet TN-22 registry record.