Danish Trial of Weight Loss to Reduce Atrial Fibrillation Progression

Trial details

Who runs it

Axel Brandes

Trial code

NCT07816744

Record updated

5 October 2026

Original description

Obesity is an important risk factor for the development and progression of atrial fibrillation. Sustainable weight loss likely reduces the burden of atrial fibrillation, which has yet to be proven in adequately sized randomised trials.Read full original descriptionShow less

The Danish Trial of Weight Loss to Reduce Atrial Fibrillation Progression

Obesity is an important risk factor for the development and progression of atrial fibrillation. Sustainable weight loss likely reduces the burden of atrial fibrillation, which has yet to be proven in adequately sized randomised trials.

In a national, multicentre randomised trial we will test, whether a sustainable weight loss of more than 10% reduces atrial fibrillation progression and burden in patients with symptomatic paroxysmal or early persistent atrial fibrillation and a body mass index ≥27 kg/m2. A total of 480 patients will be randomised in a 1:1 fashion to either a comprehensive weight loss programme of behavioural support, meal replacement and/or pharmacotherapy with a glucagon-like peptide-1 receptor agonist on top of standard care aiming at more than 10% weight loss or standard care alone. Standard care will include guideline-directed anticoagulant therapy for stroke prevention, rate and/or rhythm control treatment, and management of risk factors and underlying cardiovascular conditions. Patients in the standard care group will receive information on weight management, but no active treatment for weight loss. Patients will be enrolled during a period of two and a half years and will be followed for one year with an equal number of study visits in both study arms. All patients will receive a 14-day continuous electrocardiographic monitoring at baseline, four, eight, and 12 months.

The study endpoints will be assessed after a 4-months blanking period from month four to 12 to allow for weight loss. The primary endpoint will be a hierarchical composite of atrial fibrillation progression, symptom burden, and treatment escalation. Secondary endpoints will be a change in weight, total atrial fibrillation burden, quality of life, and metabolic and cardiovascular biomarkers from baseline to 12 months. Safety endpoints will be adverse events related to treatment with glucagon-like peptide-1 receptor agonists and weight loss. Endpoint adjudication will be blinded.

Inclusion: Symptomatic paroxysmal* or persistent** AF; Sinus rhythm at inclusion (Visit 1); BMI ≥27 kg/m2; Age>18 years; At least one 12-lead ECG or other single- or multiple-lead ECG device (e.g. Holter monitor-ing or ECG-providing wearables) documented episode during 6 months prior to inclusion; Paroxysmal AF in this trial is defined as at least 2 episodes, either self-terminating or cardioverted within 7 days, during 6 months prior to in-clusion; **Persistent AF in this study is defined as the following:; Duration of an AF episode >7 days and < 6 months; Total documented AF history < 5 years.

Exclusion: Atrial flutter as the primary arrhythmia. (Patients with previous or isolated episodes of atrial flutter may be included, provided that AF is the dominant arrhythmia and the primary target of clinical management); Incretin-based therapy (GLP-1 receptor agonists or DPP-IV inhibitors) within 30 days prior to randomization (visit 1); Scheduled for bariatric surgery during the study period; Chronic or previous acute pancreatitis; Type 1 diabetes or Type 2 diabetes on insulin treatment; History of catheter ablation for AF; Personal or family history of medullary thyroid carcinoma (MTC); History of MEN2 (Multiple Endocrine Neoplasia type 2); Severe heart failure (LVEF <40%); Severe kidney disease (eGFR<30); Implanted electronic device (pacemaker/ICD/ICM); Inability to sign informed consent; Scheduled to receive catheter ablation for AF during the study period (next 1 year); Hypertrophic cardiomyopathy, ARVC/D, non-compaction or amyloidosis; Current participation in any other clinical intervention trial that may result in changes to med-ical management during the study period; Women of childbearing potential who are not on an acceptable form of contraception; Pregnant or breastfeeding women.

ClinicalTrials.gov NCT07816744