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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/m2, 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. [ABSTRACT FROM AUTHOR]

Abstract: Glomerular filtration rate (GFR) is routinely used as a surrogate endpoint for the development of investigational drugs in clinical trials. GFR and staging of chronic kidney disease are typically assessed by measuring the concentration of endogenous serum biomarkers such as albumin and creatinine. However, creatinine is subject to high biological variability, and levels of creatinine do not rise until nearly 50% of kidney function is damaged, leading to inaccurate chronic kidney disease staging and false negatives. A newer biomarker for GFR, cystatin C, has been shown to be subject to less biological interference and more sensitive to early declines in kidney function. Cystatin C has also been shown to outperform creatinine as an indicator of true GFR and to add information about the occurrence of acute kidney injury. Comparison studies of cystatin C and creatinine continue to demonstrate its increased accuracy and sensitivity for changes in true GFR. While challenges remain for use of cystatin C, international agencies and working groups continue to validate cystatin C as a biomarker and accompanying GFR estimating equations for diagnostic and drug development use. In this review, we summarize these comparison studies, regulatory and industry guidelines, and clinical trial case studies for use of cystatin C in drug development. [ABSTRACT FROM AUTHOR]