SOCRATES-AF

WithdrawnPhase 3

Semaglutide for the Reduction of Arrhythmia Burden in Overweight AF Patients

Semaglutide for the Reduction of Arrhythmia Burden in Overweight and Obese Patients With Atrial Fibrillation (Pilot Study)

Lead sponsor

Axel Brandes

Assets

GLP-1 / incretin class catch-all / Semaglutide

Listed sites

Recruiting sites

—

Enrollment

—

actual

Study population

Atrial fibrillation, Obesity / overweight

Key I/E criterion

•BMI ≥30

Primary endpoints

•Number of Participants to Complete Recruitment•Number of Participants to Complete Follow-up•Total Resource Requirement

Identifiers

Registered as

NCT IDNCT04885634

Org study ID2021-SOCRATES-AF

Secondary ID2021-002017-34

Timeline

Milestones

Study first posted2021-05-13actual

Last update posted2023-11-03actual

Study start2022-10estimated (month precision)

Primary completion2024-01estimated (month precision)

Study completion2024-11estimated (month precision)

Assets

Investigational agents

GLP-1 / incretin class catch-all Semaglutide

Study populations

Who this study enrolls

Atrial fibrillationObesity / overweight

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Signed informed consent before any study-related activity

•≥ 18 years of age at the time of signing informed consent

•Body mass index (BMI) ≥ 30 kg/m2

•Body mass index (BMI) ≥ 27 kg/m2 and at least 1 concomitant cardiometabolic risk factor (hypertension, dyslipidemia, or obstructive sleep apnea)

•Symptomatic paroxysmal or early persistent atrial fibrillation (Paroxysmal AF: Self- terminating, in most cases within 48 hours up to 7 days. AF episodes that are cardioverted within 7 days with a documented 12 lead ECG showing sinus rhythm within the last 12 months; early persistent AF: AF episodes lasting longer than 7 days, including episodes that are terminated by cardioversion, either with drugs or by direct current cardioversion, after 7 days or more. Early persistent AF in this trial is defined as persistent AF with first-time electrical cardioversion (ECV) or a maximum of 1 previous ECVs.)

Exclusion criteria

•General exclusion criteria

–Age ≥75 years

–History of type 1 or 2 diabetes (history of gestational diabetes is allowed)

–Known or suspected hypersensitivity to study medication or related products

–Treatment with GLP-1 receptor agonists within the last 3 months before randomisation

–Treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors

–Alcohol/drug abuse

–Pregnant or breastfeeding women

–Fertile women not using chemical (tablet/pill, depot injection of progesterone, sub- dermal gestagen implantation, hormonal vaginal ring or transdermal hormonal patch) or mechanical (spirals) contraceptives

–Active malignancy, unless in complete remission for ≥5 years

–Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC)

–Personal history of non-familial medullary thyroid carcinoma

–Inflammatory bowel diseases

–Acute or chronic pancreatitis

–Obesity induced by other endocrinologic disorders (e.g. Cushing's Syndrome)

–Current history of treatment with medications that may cause significant weight gain, within the last 3 months before screening, including systemic corticosteroids (except for a short course of treatment, i.e. 7-10 days), tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g. imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium)

–Diet attempts using herbal supplements or over-the-counter medications within 3 months before screening

–Current participation (or within the last 3 months) in an organised weight reduction programme or currently using or used within 3 months before screening: pramlintide, sibutramine, orlistat, zonisamide, topiramate, phentermine (either by prescription or as part of a clinical trial)

–Severe chronic obstructive pulmonary disease

–Uncontrolled treated/untreated hypertension (systolic >180 mmHg and/or diastolic >105 mmHg)

–Previous or planned surgical treatment for obesity

–Life expectancy <2.5 years

–Other concomitant disease or treatment that according to the investigator's assessment makes the subject unsuitable for study participation

–Participation in any other clinical intervention trial

–Previous participation in the SOCRATES-AF pilot study

–Inability to sign informed consent

•Exclusion criteria related to a cardiac condition

–Previous or planned AF ablation

–Previous use of continuous prophylactic class I or III antiarrhythmic drugs

–Long-standing persistent or permanent AF

–Overall clinical history of persistent AF ≥5 years

–ECG suggestive of malignant ventricular arrhythmia

–Prolonged corrected QT-interval (>500 ms), unless caused by bundle branch block

–Myocardial infarction (MI) within the last 3 months before screening

–Coronary revascularization within the last 3 months before screening

–Planned coronary revascularisation

–Cardiac surgery within the last 12 months before screening

–Obstructive hypertrophic cardiomyopathy

–Clinically significant valvular heart disease

–Left ventricular (LV) dysfunction (HFrEF with left ventricular ejection fraction (LVEF) <45%) unless elicited by AF

–Hospitalization due to decompensated heart disease within 30 days prior to randomization

–Congestive heart failure (NYHA class IV)

–Current myocardial or pericardial infection

–Permanent pacemaker (PM) in use or implantable cardioverter defibrillator (ICD)

–Patient cannot be prescribed non-vitamin K oral anticoagulant (NOAC)

–perform physical exercise for medical or personal reasons

•Exclusion criteria based on laboratory abnormalities

–Liver disease with increased plasma alanine aminotransferase (ALAT) levels of more than three times the upper limit of normal

–Renal dysfunction (eGFR <30 ml/min), dialysis or kidney transplant

–Clinically manifest thyroid dysfunction requiring therapy. After successful treatment of thyroid dysfunction, subjects may be enrolled, when thyroid function is controlled.

–HbA1c >6.5% measured at screening

Endpoints (5)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Cardiovascular outcomes

Safety / tolerability / PK

Cardiovascular outcomes

1 endpoint

Secondary/protocol endpoint

Efficacy of Semaglutide in Reducing AF Recurrences in Obese AF Patients

Time frame:Up to 75 weeks, until final follow-up

Atrial-fibrillation composite

event count, event

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

Incidence of adverse effects of Semaglutide in overweight and obese AF patients

Time frame:Up to 75 weeks, until final follow-up

Treatment-emergent AEs (any)

event count, event

Other (unclassified)

3 endpoints

Primary/protocol endpoint

Number of Participants to Complete Recruitment

Time frame:Up to 68 weeks, until end of treatment

descriptive

Primary/protocol endpoint

Number of Participants to Complete Follow-up

Time frame:Up to 75 weeks, until final follow-up

threshold achievement, descriptive

Primary/protocol endpoint/low confidence

Total Resource Requirement

Time frame:Up to 75 weeks, until final follow-up

descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.