TN-10: Teplizumab to delay clinical type 1 diabetes in at-risk relatives (Stage 2)

What this trial tested, and why it matters

For decades, type 1 diabetes could only be treated after it was diagnosed — once the immune system had already destroyed most insulin-producing beta cells. This trial, known as TN-10, asked a more ambitious question: in people who are clearly on the path to type 1 diabetes but don't yet have it, can a short drug course slow the immune attack and push back the day they need insulin?¹ It is the single most important prevention trial in the field, because it produced the first therapy ever shown to delay type 1 diabetes.²

Who it was for

The trial enrolled relatives of people with type 1 diabetes, aged 8 to 45, who were at very high risk: they had two or more diabetes-related autoantibodies (a sign the immune attack is already underway) together with abnormal blood-sugar handling on a glucose-tolerance test — what is now called Stage 2 disease.¹ Most participants (about 72%) were 18 or younger.¹

How it was designed

This was a Phase 2, randomized, double-blind, placebo-controlled trial run by the NIH-funded TrialNet network.¹³ A total of 76 participants were randomly assigned — 44 to teplizumab and 32 to placebo — and given a single 14-day course by intravenous infusion.¹ Teplizumab is an anti-CD3 antibody that dampens the T cells driving the attack on beta cells.¹ Participants were then followed with glucose-tolerance tests every 6 months to see who progressed to clinical (Stage 3) diabetes.¹

Key results

The single course meaningfully delayed disease. In the 2019 primary report, the median time to a type 1 diabetes diagnosis was 48.4 months with teplizumab versus 24.4 months with placebo — about a 2-year delay — with a hazard ratio of 0.41.¹ Diabetes developed in 43% of treated participants versus 72% on placebo.¹ On longer follow-up (median ~923 days), the gap widened to a median of 59.6 versus 27.1 months, and half of treated participants still had not developed diabetes, compared with 22% on placebo.⁴ The drug also improved and stabilized beta-cell (C-peptide) function.⁴ Side effects were manageable — mainly rash and a temporary drop in lymphocytes.¹

What it means and what's next

These results directly supported the FDA's November 2022 approval of teplizumab (brand name Tzield) — the first drug cleared to delay the onset of Stage 3 type 1 diabetes in people aged 8 and older with Stage 2 disease.⁵⁶ This makes early screening valuable: finding at-risk people before symptoms now opens a real treatment option. Research continues on giving teplizumab earlier and on combining it with other therapies to extend the delay further.⁶

References

1. Herold KC, Bundy BN, Long SA, et al. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med (2019). https://doi.org/10.1056/NEJMoa1902226 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰

2. U.S. Food and Drug Administration. FDA approves first drug that can delay onset of type 1 diabetes (FDA Update, Jan 1, 2023; original approval Nov 17, 2022). https://www.fda.gov/media/164864/download ↩

3. National Library of Medicine. AntiCD3 Mab (Teplizumab) For Prevention of Diabetes In Relatives At-Risk for Type 1 Diabetes Mellitus (NCT01030861). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT01030861 ↩

4. Sims EK, Bundy BN, Stier K, et al. Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med (2021). https://doi.org/10.1126/scitranslmed.abc8980 ↩ ↩²

5. U.S. Food and Drug Administration. FDA approves first drug that can delay onset of type 1 diabetes (FDA Update, Jan 1, 2023; original approval Nov 17, 2022). https://www.fda.gov/media/164864/download ↩

6. U.S. Food and Drug Administration. Drug Trials Snapshots: TZIELD. FDA (2022). https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-tzield ↩ ↩²