Table 2.
Secondary prevention studies.
| Trial acronym | Population | Intervention | Multi-center? | Blinding | Primary Outcome | Follow-up duration | Positive? | Hazard ratio (95%CI) vs. control |
|---|---|---|---|---|---|---|---|---|
| Näntö-Salonen 200826 | 264 infants with high-risk HLA genotype and their siblings with high-risk HLA and multiple Aab+ | Intranasal daily recombinant human short-acting insulin vs. placebo | Yes | Double | Time to diabetes |
Insulin: 1.7 years (IQR 0.7–3.0) Placebo: 2.0 years (IQR 0.8–3.2) |
No |
• Infants: 1.2 (0.68–2.0) • Infants + siblings: 0.98 (0.67–1.4) |
| Lampeter 199825 (DENIS) | 55 Islet-cell Aab+ siblings of individuals with T1D | 1.2 g/m2/day Endur-Amide (nicotinamide) vs. placebo | Yes | Double | Time to diabetes | 2.1 years, maximum 3.8 | No | 0.79 (0.25–3.4) |
| Gale 200420 (ENDIT) | 552 Islet-cell Aab+ relatives with nondiabetic OGTT | 1.2 g/m2 po modified release nicotinamide x 5 years vs. placebo | Yes | Double | Time to diabetes | 5 years (intended for all, but only reached by 88%) | No | 1.1 (0.78, 1.5) |
| Skyler 200217 (DPT-1) | 339 Islet-cell Aab+ first-degree relatives with the absence of low-risk HLA and low first-phase insulin response or dysglycemia | 0.25U/kg ultralente + annual 4-day continuous insulin infusion vs. no intervention | Yes | None | Time to diabetes | 1345 days, IQR 784–1737 | No | 0.96 (0.69–1.3) |
| Skyler 200528 (DPT-1) | 372 Islet-cell and insulin Aab + relatives with the absence of low-risk HLA, higher first-phase insulin response, and normal OGTT | Oral insulin (7.5 mg/day) vs. placebo | Yes | Double | Time to diabetes | 4.3 years (IQR: 928–1988 days) | No | 0.76 (0.51‚1.1) |
| • Vehik 201131 (F/u) | • 303/372 | • 9.1 years | ||||||
| • Butty 200818 (Precision) | • 638 from parenteral and oral insulin trials | • n/a | ||||||
| Krischer 201724 (TN07) | 560 Multiple Aab+ relatives with insulin Aab + and high or low first-phase insulin response | 7.5 mg daily po recombinant human insulin vs. placebo | Yes | Double | Time to diabetes | 2.7 years (IQR 1.5–4.7 years) | No | 0.83 (0–1.07) |
| • Sosenko 202029 (Precision: DPT-1 and TN07) | • 208 with high DPTRS | • n/a | • DPT-1: 0.494 (0.26, 0.96) TN07: 0.70 (0.43, 1.2) | |||||
| EldingLarsson 201819 (DiAPREV-IT) | 50 Multiple Aab+ children with GAD Ab+ | 20 ug sc injections of GAD-Alum monthly x 2 vs. placebo | No | Double | Other: safety | 4.92 years (range: 0.47–5.0) | n/a | 0.77 (0.30, 1.9) |
| Herold 201921 (TN10) | 76 Multiple Aab+ relatives with dysglycemia | 14-day course of IV Teplizumab vs. placebo | Yes | Double | Time to diabetes | 745 days (range 74–2683) | Yes | 0.41(0.22–0.78) |
| • Sims 202127 (F/u) | • 923 days | • 0.457 |
Follow-up or precision studies describing a randomized trial that is already included in the table are listed as bulleted subheadings.
T1D type 1 diabetes, HLA human leukocyte antigen, Aab autoantibody, n/a not applicable, Aab+ autoantibody-positive, DENIS The Dutch Nicotinamide Intervention Study, ENDIT European Nicotinamide Diabetes Intervention Trial, OGTT oral glucose tolerance test, Po per oral/orally, DPT-1 Diabetes Prevention Trial Type 1 Diabetes, F/u follow-up, TN07 TrialNet 07 trial, DPTRS diabetes prevention trial-type 1 risk score, DiAPREV-IT diabetes prevention–immune tolerance trial, GAD glutamic acid decarboxylase, Sc subcutaneous, TN10 TrialNet 10 trial, IV intravenous.