GLP-1 receptor agonists in patients with chronic kidney disease and either overweight or obesity.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as game-changers across the cardiovascular-kidney-metabolic (CKM) spectrum: overweight/obesity, type 2 diabetes mellitus (T2DM) and associated chronic kidney disease (CKD) and cardiovascular disease (CVD). Liraglutide, semaglutide and tirzepatide are European Medicines Agency approved to improve metabolic control in T2DM and to decrease weight in persons with obesity [body mass index (BMI) ≥30 kg/m²] or with overweight (BMI ≥27 kg/m²) associated with weight-related comorbidities such as hypertension, dyslipidaemia, CVD and others. Additionally, liraglutide and semaglutide are approved to reduce CVD risk in patients with CVD and T2DM. Semaglutide is also approved to reduce CVD risk in patients with CVD and either obesity or overweight and in phase 3 clinical trials showed kidney and cardiovascular protection in patients with T2DM and albuminuric CKD (FLOW trial) as well as in persons without diabetes that had CVD and overweight/obesity (SELECT trial). Thus, nephrologists should consider prescribing GLP-1 RAs to improve metabolic control, reduce CVD risk or improve kidney outcomes in three scenarios: patients with overweight and a related comorbid condition such as hypertension, dyslipidaemia or CVD, patients with obesity and patients with T2DM. This review addresses the promising landscape of GLP-1 RAs to treat persons with overweight or obesity, with or without T2DM, within the context of CKD, assessing their safety and impact on weight, metabolic control, blood pressure and kidney and cardiovascular outcomes, as part of a holistic patient-centred approach to preserve CKM health.