Hemodynamic Changes in Response to GLP-1 Treatment in ICD and CRT Patients: Insights From HeartLogic Sensor Data

Abstract Background Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy is increasingly used, but the physiological effects in patients with heart failure and reduced ejection fraction (HFrEF) remain uncertain. Continuously collected data from implantable cardiac devices may enable evaluation of drug effects in a real-world setting. Methods In a nationwide Danish retrospective matched cohort study, GLP-1RA initiators with implantable cardiac devices were matched 1:5 to unexposed device recipients by sex and age. Sensor data were assessed from 30 days before to 30 days after initiation. Primary outcomes were changes in heart rate and thoracic impedance. Analyses were adjusted for baseline sensor value, BMI category, hypertension, and type 2 diabetes. Prespecified subgroup analyses were performed in patients with HFrEF. Results In 666 patients (111 GLP-1RA initiators, 555 matched controls), semaglutide was used in 95% of initiators. Compared with controls, GLP-1RA initiation was associated with higher night heart rate (adjusted difference 2.12 bpm; 95% CI, 1.38 to 2.87), higher daily heart rate (1.46 bpm; 95% CI, 0.65 to 2.06), and higher thoracic impedance (0.66 Ω; 95% CI, 0.17 to 1.15) (all P0.01). S1 amplitude decreased (-0.09 mG; 95% CI, -0.14 to -0.04; P0.01). Heart rate increases followed a stepwise pattern across semaglutide dose levels, with an average increase of 2.5 bpm per dose escalation. Findings were directionally consistent in patients with HFrEF (GLP-1RA n=80), with no evidence of effect modification. Conclusion GLP-1RA initiation was associated with measurable changes in device-derived physiology. Larger studies are needed to evaluate clinical implications, including in HFrEF. Trial registration Clinicaltrials.gov (NCT06099158).