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.

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.