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Phase 3CompletedNCT00004984

DPT-1: Diabetes Prevention Trial-Type 1 (parenteral and oral insulin)

What this study tests

A landmark NIH prevention trial that screened over 100,000 relatives of people with type 1 diabetes to test whether giving insulin (by injection or by mouth) before diagnosis could delay or prevent the disease. Neither approach worked overall, but a subgroup signal from the oral-insulin arm seeded the later TrialNet oral insulin study (TN-07).

Editorial review: .

Registry checked: 2026-09-17. Registry’s own update: 2020-04-24.

Most recent recorded citation date: 2002-07-01. 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

Full sources ↓Full discussion ↓Report an issue →

Evidence at a glance

Who can enter the study?
Nondiabetic first-degree relatives (ages 3-45) or second-degree relatives (ages 3-20) of someone with type 1 diabetes who tested positive for islet-cell antibodies and then completed genetic, immune, and metabolic risk staging. The higher-risk relatives (projected 5-year risk over 50%) entered the parenteral-insulin trial; intermediate-risk relatives (5-year risk roughly 26-50%) who were also positive for insulin autoantibodies entered the oral-insulin trial. People who already had diabetes, had used insulin/diabetes medication, or carried the protective HLA-DQA1*0102/DQB1*0602 haplotype 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
Neither approach prevented type 1 diabetes overall. In the injected-insulin trial (339 high-risk relatives), diabetes developed in 69 of the insulin group versus 70 of the observation group, with nearly identical yearly progression rates (15.1% vs 14.6%) and no overall benefit (relative risk 0.96). In the oral-insulin trial (372 relatives), diabetes developed in 44 on oral insulin versus 53 on placebo (6.4% vs 8.2% per year; hazard ratio 0.764, not significant, P=0.189). However, in an exploratory, post hoc subgroup with confirmed high insulin autoantibody levels (IAA at or above 80 nU/ml on two occasions), oral insulin appeared to slow progression (6.2% vs 10.4% per year; hazard ratio 0.566, P=0.015) - a hypothesis-generating signal that motivated a follow-up trial.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

  • Diagnosis of type 1 diabetes (development of clinical diabetes), assessed by oral glucose tolerance testing every 6 months
  • Annualized rate of progression to type 1 diabetes

The full picture

What was tested and why it matters. The Diabetes Prevention Trial-Type 1 (DPT-1) asked a bold question: if you find people who are on the path to type 1 diabetes before they get sick, can giving them insulin early teach the immune system to stand down and delay or prevent the disease?1 This was one of the first large trials to test prevention using the body's own target molecule (insulin) as a kind of "tolerance" therapy.2

Who it was for. DPT-1 enrolled close relatives of people with type 1 diabetes, because they carry higher genetic risk. Researchers screened 84,228 relatives for the injected-insulin study and 103,391 for the oral-insulin study, looking for islet-cell antibodies (an early sign of immune attack), then narrowed down with genetic, immune, and metabolic tests to find those most likely to progress.13 Eligible relatives were ages 3-45 (first-degree) or 3-20 (second-degree).4

Design. DPT-1 was really two NIH-funded, randomized Phase 3 trials run in parallel across 15 sites in the US and Canada.4 Higher-risk relatives (over 50% projected 5-year risk) were randomized to low-dose injected insulin (with annual intravenous insulin infusions) or to close observation - 339 people, followed a median of 3.7 years.1 Intermediate-risk relatives with insulin autoantibodies were randomized to an oral insulin capsule (7.5 mg/day) or placebo - 372 people, followed a median of 4.3 years.3 The goal in both was to see who developed diabetes, checked every 6 months.13

Key results. Neither approach prevented diabetes overall. Injected insulin: 69 cases vs 70 in the observation group; yearly progression 15.1% vs 14.6% (relative risk 0.96).1 Oral insulin: 44 cases vs 53 on placebo (6.4% vs 8.2% per year; hazard ratio 0.764, not statistically significant).3 But in an exploratory, post hoc subgroup with confirmed high insulin-autoantibody levels (IAA at or above 80 nU/ml on two occasions), oral insulin appeared to slow progression (6.2% vs 10.4% per year; hazard ratio 0.566, P=0.015).3

What it means / what's next. DPT-1 showed that high-risk relatives could be identified and enrolled in a large, multisite prevention trial, with most new cases caught while still asymptomatic.13 The oral-insulin subgroup signal was promising enough to seed a dedicated follow-up trial in TrialNet (the oral insulin study, TN-07).3

Sources

  1. [1]
    Diabetes Prevention Trial-Type 1 Diabetes Study Group. Effects of insulin in relatives of patients with type 1 diabetes mellitus. *N Engl J Med* (2002), via PubMed · Peer-reviewed study

    Diabetes Prevention Trial-Type 1 Diabetes Study Group. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med (2002), via PubMed.

    Diabetes Prevention Trial-Type 1 Diabetes Study Group. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 346:1685-1691 (2002), via PubMed.

  2. [2]
    The DPT-1 trial: a negative result with lessons for future type 1 diabetes prevention. · Peer-reviewed study · 2002-07-01

    Pozzilli P. The DPT-1 trial: a negative result with lessons for future type 1 diabetes prevention. Diabetes Metab Res Rev (2002), via PubMed.

  3. [3]
    Skyler JS, Krischer JP, Wolfsdorf J, et al. Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial-Type 1. *Diabetes Care* 28:1068-1076 (2005), via PubMed · Peer-reviewed study

    Skyler JS, Krischer JP, Wolfsdorf J, et al. Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial-Type 1. Diabetes Care 28:1068-1076 (2005), via PubMed.

  4. [4]
    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The Diabetes Prevention Trial of Type 1 Diabetes (DPT-1). *ClinicalTrials.gov* (NCT00004984) · Trial registry

    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The Diabetes Prevention Trial of Type 1 Diabetes (DPT-1). ClinicalTrials.gov (NCT00004984).