Preserving beta cell function in children and adolescents with newly diagnosed stage 3 type 1 diabetes: per-protocol population analysis from the PROTECT randomised trial.

In 30 seconds

This pre-specified per-protocol analysis of the multicentre, randomised PROTECT trial assessed teplizumab in children and adolescents aged 8–17 years with newly diagnosed stage 3 type 1 diabetes. Among 275 participants meeting per-protocol criteria, two 12-day intravenous courses of teplizumab were compared with placebo. At week 78, the between-group least-squares mean difference in change in stimulated C-peptide from baseline was 0.14 nmol/l (95% CI 0.10, 0.18; p<0.001), favouring teplizumab. Insulin dose was lower and time in range higher with teplizumab; C-peptide findings were consistent across the reported subgroups.

Key findings

• At week 78, the stimulated C-peptide change favoured teplizumab by 0.14 nmol/l (95% CI 0.10, 0.18; p<0.001).
• Teplizumab reduced exogenous insulin dose versus placebo at week 78 (LS mean difference -0.17 U kg -1 day -1 ; 95% CI -0.26, -0.08; p<0.001).
• Time in range was higher with teplizumab at week 78 (LS mean difference 6.17%; 95% CI 0.13, 12.2; p<0.05).
• Higher C-peptide levels with teplizumab were observed regardless of HLA-DR3/HLA-DR4 status or baseline type 1 diabetes autoantibodies.

Why it matters

Preserving endogenous beta cell function after diagnosis may accompany lower insulin requirements and improved time in range, outcomes relevant to diabetes management in young people. This analysis also suggests that the C-peptide benefit was not confined to the HLA or autoantibody subgroups examined. The findings add detail to the trial’s efficacy assessment but should be interpreted in the context of its per-protocol population.

What to keep in mind

The per-protocol analysis excluded participants who did not meet treatment-adherence and other eligibility criteria, so its findings may not fully reflect outcomes in all randomised participants.