How to individualize renoprotective therapy in obese patients with chronic kidney disease: a commentary by the Diabesity Working Group of the ERA

The interrelated pandemics of obesity and type 2 diabetes mellitus (T2DM) are fuelling an increase in the prevalence of chronic kidney disease (CKD), which amplifies the risk of cardiovascular events and may progress to end-stage kidney disease (ESKD). Treatment options for such patients have rapidly expanded over the past decade and continue to evolve. Herein, we primarily focus on glucagon-like peptide-1 receptor agonists (GLP-1RAs) and their role in the management of CKD in the setting of overweight/obesity and T2DM. Recommendations from the recent Kidney Disease: Improving Global Outcomes CKD guidelines are summarized and new evidence arising since publication of these guidelines is highlighted. We review clinical studies supporting the role of GLP-1RAs in patients with diabesity and CKD, including the FLOW trial, as well as exploring potential mechanisms of their nephroprotective effects. Their role in the management of patients with ESKD on maintenance dialysis and after kidney transplantation, while less evidence-based, is also discussed. The potential for other gut hormone-based therapies, including GLP-1/glucose-dependent insulinotropic polypeptide dual agonists (tirzepatide), triple agonists (incorporating glucagon agonism) and amylin analogues to improve cardiovascular and kidney outcomes in patients with CKD, is explored. We highlight the role of novel therapies distinct from the gut-kidney axis, including non-steroidal mineralocorticoid receptor antagonists (nsMRAs). We outline the potential for multitarget therapy incorporating renin-angiotensin-aldosterone system inhibitors, sodium-glucose co-transporter-2 inhibitors, incretin-based treatments and nsMRAs to improve cardiovascular and kidney outcomes in patients with overweight/obesity and T2DM. Current unknowns in the timing and sequence of multitarget therapy in patients with CKD are emphasized. Priority research questions for the future are highlighted throughout the review.