{
  "abstract": "Objectives To assess the beneficial and harmful effects of regular human insulins versus rapid-acting insulin analogues in children and adolescents with type 1 diabetes.Design Systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.Data sources CENTRAL, MEDLINE, Embase, LILACS and other sources from inception to 30 January 2026.Study selection Randomised clinical trials comparing regular human insulins versus rapid-acting insulin analogues (insulin aspart, lispro, glulisine) in children and adolescents with type 1 diabetes.Analyses Data were analysed using meta-analysis and trial sequential analysis. Risk of bias was assessed using the Cochrane Risk of Bias tool, V.2, and the certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.Primary outcomes Severe hypoglycaemia, ketoacidosis and serious adverse events.Results 10 trials randomising 1107 participants were included. The certainty of evidence was very low mainly due to high risk of bias and small sample sizes. Meta-analysis showed no evidence of a difference between regular human insulins and rapid-acting insulin analogues on severe hypoglycaemia (risk ratio (RR) 1.28, 95% CI 0.81 to 2.03; I 2=0.0%; p=0.2851; nine trials), ketoacidosis (RR 0.88, 95% CI 0.26 to 2.93; I2=0.0%; p=0.8593; two trials) and serious adverse events (RR 1.00, 95% CI 0.44 to 2.25; I2=0.0%; p=0.9958; two trials). Trial sequential analysis showed that all meta-analyses of primary outcomes were underpowered.Conclusions Current research shows no differential effects between regular human insulins and rapid-acting insulin analogues for children and adolescents with type 1 diabetes, but the evidence is very uncertain.PROSPERO registration number CRD42024508625.",
  "authors": [
    {
      "affiliations": [
        "Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark",
        "Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"
      ],
      "name": "Johanne Juul Petersen"
    },
    {
      "affiliations": [
        "Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark"
      ],
      "name": "Pascal Faltermeier"
    },
    {
      "affiliations": [
        "Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark",
        "Mental Health Services in the Capital Region of Denmark, Psykoterapeutisk Center Stolpegard, Gentofte, Denmark",
        "Department of Psychology, University of Copenhagen, Copenhagen, Denmark"
      ],
      "name": "Sophie Juul"
    },
    {
      "affiliations": [
        "Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark"
      ],
      "name": "Caroline Barkholt Kamp"
    },
    {
      "affiliations": [
        "Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark",
        "Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark",
        "Department of Cardiology, Central and West Zealand Hospital, Slagelse, Denmark"
      ],
      "name": "Christina Dam Bjerregaard Sillassen"
    },
    {
      "affiliations": [
        "Unit of Pediatrics, Hospital Vithas Almería, Instituto Hispalense de Pediatría SL, Seville, Spain",
        "Department of Nursing Physiotherapy and Medicine, Faculty of Health Sciences, University of Almeria, Almería, Spain"
      ],
      "name": "Tiago Jeronimo Dos Santos"
    },
    {
      "affiliations": [
        "Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark",
        "Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark"
      ],
      "name": "Janus Christian Jakobsen"
    }
  ],
  "title": "Regular human insulins versus rapid-acting insulin analogues in children and adolescents with type 1 diabetes: a systematic review with meta-analysis and trial sequential analysis",
  "uid": "4fd42f50-807f-5f3d-ac0c-f23c9d57ae83"
}