Prevalence of Baseline Cardiac Arrhythmias in Participants with Overweight or Obesity in Phase 1 Clinical Trials: Analysis of 24-Hour Holter Electrocardiogram Recordings

Although estimates of the prevalence of cardiac arrhythmias in healthy volunteers exist, there is a lack of baseline data in other specific populations, such as people living with overweight and obesity, who are increasingly involved in clinical trials. This study investigated the baseline prevalence of arrhythmias in participants with overweight or obesity in 2 phase 1 trials of weight management medications (NCT03661879, NCT03308721). Participants aged 18-55 years, without a history of cardiovascular disease, and with body mass index (BMI) of 25.0-39.9 kg/m(2), were screened for abnormalities in vital signs, electrocardiogram (ECG) recordings, and electrolytes. Baseline 24-hour ECG (Holter) data were collected and manually reviewed by a cardiologist. The primary endpoint was the proportion of participants with >= 1 episode of the predefined cardiac arrhythmias. Continuous 12-lead ECG data were obtained from 207 participants. Most arrhythmias occurred in <3% of participants. Atrioventricular blocks and other potentially malignant arrhythmias were uncommon. There were no associations with age, sex, or BMI. Prevalence of atrioventricular blocks, nonsustained ventricular tachycardia, and other potentially malignant arrhythmias mirrored those reported in healthy participants with normal weight. In clinical trials of weight management medication, knowledge of the baseline prevalence of arrhythmias in people with overweight and obesity may inform trial eligibility criteria, improve on-trial decisions, and could be useful in discussions with health authorities. Baseline Holter readings and real-time ECG telemetry monitoring should be considered in such trials if arrhythmia risk is intrinsic to the molecule, or when signals have been observed in preclinical studies.

Automated summary

Although prevalence of cardiac arrhythmias in healthy volunteers has been estimated, there is limited baseline data for populations such as overweight and obese individuals, who are increasingly participating in clinical trials. This study examined the baseline prevalence of arrhythmias in overweight or obese participants in two phase 1 trials of weight management medications. The findings showed that most arrhythmias were rare, and the prevalence mirrored that of healthy participants with normal weight. Knowledge of the baseline prevalence of arrhythmias in overweight and obese individuals can inform trial eligibility criteria and improve decision-making in weight management clinical trials.