{
  "abstract": "Introduction Type 2 diabetes (T2D) presents a global healthcare burden. Despite widespread use of non-insulin glucose lowering therapies, many individuals still require insulin to achieve recommended target glycated haemoglobin (HbA1c). Insulin injections improve HbA1c but can lead to problematic hypoglycaemia. The objective of this study is to determine whether fully closed-loop insulin delivery improves HbA1c at 26 weeks compared with standard insulin therapy with continuous glucose monitoring (CGM) in adults with T2D.Methods and analysis This study adopts an open-label, multinational, randomised, single-period parallel design and aims to randomise 224 adults with T2D to either standard insulin therapy with CGM (control group) or fully closed-loop insulin delivery (intervention group) for a period of 26 weeks. Participants will complete a run-in period of 2–3 weeks wearing a masked CGM followed by randomisation to either the control or intervention group. The primary endpoint is the between-group difference in HbA1c at 26 weeks. Key endpoints include time in target glucose range (3.9–10.0 mmol/L), mean sensor glucose, time above range (>10.0 mmol/L) and non-inferiority for time below target (<3.9 mmol/L) over the 26-week study period. Secondary outcomes include standard CGM metrics, binary metrics for HbA1c, total daily insulin dose, body mass index, blood pressure, fasted lipid profile, renal function and liver function. Safety will be assessed by the frequency of severe hypoglycaemic episodes and other adverse events. Utility will be assessed by CGM and closed-loop system use. The impact of fully closed-loop will be assessed using validated questionnaires and interviews.Ethics and dissemination The study has received ethical approval from the East of England Cambridgeshire and Hertfordshire Research Ethics Committee (24/EE/0149) in the UK. Ethical approval for non-UK site has been obtained by local Research Ethics Committees.Results will be disseminated by peer-reviewed publications and conference presentations, and findings will be shared with people living with diabetes, healthcare providers and relevant stakeholders.Trial registration number NCT06579404.",
  "authors": [
    {
      "affiliations": [
        "Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, England, UK"
      ],
      "name": "R Seese"
    },
    {
      "affiliations": [
        "Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, England, UK",
        "Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"
      ],
      "name": "CK Boughton"
    },
    {
      "affiliations": [
        "Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, England, UK"
      ],
      "name": "FT Tseung"
    },
    {
      "affiliations": [
        "Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, England, UK"
      ],
      "name": "R Uy"
    },
    {
      "affiliations": [
        "Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, England, UK"
      ],
      "name": "ME Wilinska"
    },
    {
      "affiliations": [
        "Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK",
        "Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"
      ],
      "name": "H Thabit"
    },
    {
      "affiliations": [
        "King’s College Hospital, King’s College Hospital NHS Foundation Trust, London, UK"
      ],
      "name": "YS Cheah"
    },
    {
      "affiliations": [
        "Norwich Medicine School, University of East Anglia, Norwich, UK",
        "Norfolk and Norwich University Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK"
      ],
      "name": "S Neupane"
    },
    {
      "affiliations": [
        "Department of Diabetes, School of Cardiovascular, Metabolic Medicine and Sciences, King’s College London, London, UK",
        "Department of Diabetes and Endocrinology, Guy’s & St Thomas’ NHS Foundation Trust, London, UK",
        "Institute of Diabetes, Endocrinology and Obesity, King’s Health Partners, London, UK"
      ],
      "name": "S Hussain"
    },
    {
      "affiliations": [
        "Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester, UK"
      ],
      "name": "P Choudhary"
    },
    {
      "affiliations": [
        "School of Medicine, University of Nottingham, Nottingham, UK",
        "University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK"
      ],
      "name": "EG Wilmot"
    },
    {
      "affiliations": [
        "Inselspital University Hospital Bern, Bern, Switzerland"
      ],
      "name": "L Bally"
    },
    {
      "affiliations": [
        "University of Toulouse, Toulouse, France"
      ],
      "name": "H Hanaire"
    },
    {
      "affiliations": [
        "Medical University of Graz, Graz, Austria"
      ],
      "name": "JK Mader"
    },
    {
      "affiliations": [
        "Institute for Clinical and Experimental Medicine, Prague, Czech Republic"
      ],
      "name": "M Haluzík"
    },
    {
      "affiliations": [
        "Department of Medicine St. Vincent’s Hospital Melbourne, The University of Melbourne, Melbourne, Victoria, Australia",
        "Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia"
      ],
      "name": "D O’Neal"
    },
    {
      "affiliations": [
        "School of Population Health Sciences, The University of Edinburgh Usher Institute, Edinburgh, UK"
      ],
      "name": "J Lawton"
    },
    {
      "affiliations": [
        "School of Population Health Sciences, The University of Edinburgh Usher Institute, Edinburgh, UK"
      ],
      "name": "D Rankin"
    },
    {
      "affiliations": [
        "The Jaeb Center for Health Research, Tampa, Florida, USA"
      ],
      "name": "C Kollman"
    },
    {
      "affiliations": [
        "Diabetes Research Group, Swansea University, Swansea, UK"
      ],
      "name": "G Dunseath"
    },
    {
      "affiliations": [
        "Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, England, UK"
      ],
      "name": "R Hovorka"
    }
  ],
  "title": "Assessing the efficacy, safety and utility of fully closed-loop insulin delivery compared to standard insulin therapy with a continuous glucose monitor in adults with type 2 diabetes (COYOTE study): a randomised parallel study protocol",
  "uid": "ce7581e2-8593-5e9a-98ed-9914b5889ef4"
}