TN-09: Abatacept (CTLA4-Ig) in recent-onset type 1 diabetes
What this study tests
A randomized, double-blind, placebo-controlled Phase 2 trial (TrialNet TN-09) testing whether the T-cell co-stimulation modulator abatacept could slow the loss of insulin-producing beta cells in people recently diagnosed with type 1 diabetes. Two years of abatacept preserved C-peptide and delayed its decline by about 9.6 months, but the benefit plateaued after the first 6 months of dosing.
Editorial review: .
Registry checked: 2026-09-17. Registry’s own update: 2020-05-06.
Most recent recorded citation date: 2020-03-12. Only explicit date metadata is included; an undated citation may be newer. This does not mean every claim was reviewed on that date.
Trial status, labels and access can change between reviews. How we review the evidence · How to read the evidence
Evidence at a glance
- Who can enter the study?
- For people aged 6–45 diagnosed with type 1 diabetes within the previous 100 days who had at least one diabetes-related autoantibody and detectable insulin production (stimulated C-peptide above 0.2 pmol/mL). People with immune deficiency, active or chronic infection (including HIV or hepatitis B/C), a positive TB test, prior cancer, or who were pregnant/breastfeeding were excluded. Registered eligibility ↗Enrollment criteria describe who may enter. They do not establish who was analyzed or the denominator for a reported result.
- Reported benefit and results
- Over 2 years, abatacept slowed the loss of beta-cell function: adjusted C-peptide was 59% higher than placebo (95% CI 6.1–112%; p=0.0029), equivalent to delaying C-peptide decline by about 9.6 months. Notably, the decline ran parallel to placebo after the first ~6 months, suggesting the drug acts mainly early. One year after infusions stopped (3 years from diagnosis), the gap persisted: C-peptide 0.217 vs 0.141 nmol/L (p=0.046), about a 9.5-month delay, with lower HbA1c (7.64% vs 8.55%; p<0.005). Insulin dose differences had evened out by year 3. The trial reported no excess infections or neutropenia.Read the result sources and their limitations →
- Important harms
- Read the reported results, safety discussion and original sources. A separate harms summary is not available; this does not establish safety.
- Research access and approval
- Study regions: United States, Canada. A trial listing does not establish product approval or current recruitment at a particular site. Check the study’s current entry requirements.
- What remains uncertain?
- Read the full discussion and original sources for study limitations. Planned endpoints and completion dates are not results.
Research status alone does not establish approval, clinical benefit or local availability.
Primary endpoints
- Baseline-adjusted geometric mean 2-hour area-under-the-curve (AUC) serum C-peptide after a mixed-meal tolerance test at 2 years
The full picture
What was tested and why it matters
Type 1 diabetes happens when the immune system's T cells mistakenly destroy the insulin-producing beta cells in the pancreas. For a T cell to switch fully "on," it needs two signals: it must see its target, and it must receive a second "co-stimulation" signal. Abatacept (CTLA4-Ig) is a fusion protein that blocks that second signal, so wandering T cells never become fully activated.1 This trial — TrialNet study TN-09 — asked a simple question: if you dampen T-cell activation soon after diagnosis, can you protect the beta cells that are still alive?1
This matters because people newly diagnosed with type 1 diabetes usually still make some of their own insulin, and holding onto even a little is linked to steadier glucose and fewer complications. A therapy that preserves that capacity could make the disease milder and easier to manage.2
Who it was for
The trial enrolled people aged 6–45 who had been diagnosed within the previous ~100 days, still had measurable insulin production, and carried at least one diabetes-related autoantibody.3
How it was designed
This was a multicenter, double-blind, randomized, placebo-controlled Phase 2 trial at sites across the United States and Canada.13 112 participants were randomly assigned 2:1 to abatacept (77 people) or placebo (35 people) and received 27 intravenous infusions over 2 years.1 Neither participants nor staff knew who got which.1 The main measure was how much insulin (gauged by C-peptide) people still made during a standardized meal test after 2 years.1
Key results
Abatacept clearly slowed beta-cell loss. At 2 years, C-peptide was 59% higher with abatacept than placebo (95% CI 6.1–112%; p=0.0029) — roughly a 9.6-month delay in the decline of insulin production.1 A striking detail: after the first ~6 months of treatment, beta-cell function fell at the same rate in both groups, hinting that the drug does most of its work early, when T-cell activation is most intense.1 Safety was reassuring — no excess infections or low white-blood-cell counts.1
A follow-up one year after infusions stopped (3 years from diagnosis) found the benefit endured rather than rebounding: C-peptide was 0.217 vs 0.141 nmol/L (p=0.046), about a 9.5-month delay, and HbA1c stayed lower with abatacept (7.64% vs 8.55%; p<0.005), though insulin doses had evened out.4
What it means and what's next
TN-09 was an early proof that the immune attack is still active and treatable around the time of diagnosis. But the plateau after 6 months suggests a single agent given continuously isn't enough — the benefit waned even while dosing continued.1 These findings point toward earlier intervention (before diagnosis) and combination strategies, and abatacept has since been tested in a prevention trial in at-risk relatives.2
Sources
- [1]Orban T, Bundy B, Becker DJ, et al. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. *Lancet* (2011);378(9789):412–419 · Peer-reviewed study
Orban T, Bundy B, Becker DJ, et al. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet (2011);378(9789):412–419.
- [2]CTLA4-Ig (abatacept): a promising investigational drug for use in type 1 diabetes. · Peer-reviewed study · 2020-03-12
Rachid O, Osman A, Abdi R, Haik Y. CTLA4-Ig (abatacept): a promising investigational drug for use in type 1 diabetes. Expert Opinion on Investigational Drugs (2020);29(3):221–236.
- [3]U.S. National Library of Medicine. Intravenous CTLA4-Ig Treatment in Recent Onset Type 1 Diabetes Mellitus (NCT00505375). *ClinicalTrials.gov* · Trial registry
U.S. National Library of Medicine. Intravenous CTLA4-Ig Treatment in Recent Onset Type 1 Diabetes Mellitus (NCT00505375). ClinicalTrials.gov.
- [4]Orban T, Bundy B, Becker DJ, et al. Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: follow-up 1 year after cessation of treatment. *Diabetes Care* (2014);37(4):1069–1075 · Peer-reviewed study
Orban T, Bundy B, Becker DJ, et al. Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: follow-up 1 year after cessation of treatment. Diabetes Care (2014);37(4):1069–1075.