Journal Article

Randomised, cOntrolled Multicentre trial of 26 weeks subcutaneous liraglutide (a glucagon-like peptide-1 receptor Agonist), with or without contiNuous positive airway pressure (CPAP), in patients with type 2 diabetes mellitus (T2DM) and obstructive sleep apnoEa (OSA) (ROMANCE): study protocol assessing the effects of weight loss on the apnea–hypnoea index (AHI)

Schwab, Richard J, Needham, Alexander J, Adams, Valerie, Kemp, Graham J, Cuthbertson, Daniel J, Burgess, Malcolm, Manuel, Ari, Wilding, John PH, Weimken, Andrew, Thomas, Matthew, Craig, Sonya E, Sprung, Victoria S, Murphy, Kieran, Emegbo, Stephen

2020

Overview

IntroductionObstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM) often occur concurrently, and untreated OSA may potentially amplify the high risk of cardiovascular disease in T2DM. Compliance with continuous positive airway pressure (CPAP), the conventional treatment for OSA, can be poor and considering weight loss is the most effective treatment for OSA. This trial examines whether the glucagon-like peptide-1 receptor agonist liraglutide, a glucose-lowering therapy associated with significant weight loss used in T2DM, can improve the severity and symptoms of OSA.Methods and analysisThis is an outpatient, single-centred, open-labelled, prospective, phase IV randomised controlled trial in a two-by-two factorial design. One hundred and thirty-two patients with newly diagnosed OSA (apnoea–hypopnoea index (AHI) ≥15 events/hour), and existing obesity and T2DM (glycated haemoglobin (HbA1c) ≥47 mmol/mol), will be recruited from diabetes and sleep medicine outpatient clinics in primary and secondary care settings across Liverpool. Patients will be allocated equally, using computer-generated random, permuted blocks of unequal sizes, to each of the four treatment arms for 26 weeks: (i) liraglutide (1.8 mg once per day) alone, (ii) liraglutide 1.8 mg once per day with CPAP, (iii) CPAP alone (conventional care) or (iv) no treatment (control). The primary outcome measure is change in OSA severity, determined by AHI. Secondary outcome measures include effects on glycaemic control (glycated haemoglobin (HbA1c)), body weight and quality of life measures. Exploratory measures include measures of physical activity, MRI-derived measures of regional body composition including fat mass (abdominal subcutaneous, visceral, neck and liver fat) and skeletal muscle mass (cross-sectional analysis of thigh), indices of cardiac function (using transthoracic echocardiography) and endothelial function.Ethical approvalThe study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/1019) and it is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice.Trial registration numbersISRCTN16250774. EUDRACT No. 2014-000988-41. UTN U1111-1139-0677.

• Publisher: British Medical Journal Publishing Group,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Antidiabetics / Body composition / Body mass index / Continuous Positive Airway Pressure / Cross-Sectional Studies / Diabetes / diabetes & endocrinology / Diabetes and Endocrinology / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - drug therapy / GLP-1 receptor agonists / Glucagon / Glucagon-Like Peptide-1 Receptor / Humans / Hypertension / Insulin resistance / Liraglutide - therapeutic use / Metabolism / Multicenter Studies as Topic / Obesity / Patients / Peptides / Prospective Studies / protocols & guidelines / Quality of Life / Randomized Controlled Trials as Topic / Sleep apnea / Sleep Apnea, Obstructive - complications / Sleep Apnea, Obstructive - therapy / sleep medicine / Treatment Outcome / Weight control / Weight Loss