Beyond Obesity: The Expanding Role of Glucagon-Like Peptide-1 Agonists in Chronic Kidney Disease, Pre- and Post-Renal Transplantation

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are an established class of antidiabetic agents that have gained expanding indications in obesity and metabolic syndrome management. By mimicking endogenous incretin activity, these agents enhance glucose-dependent insulin secretion, suppress glucagon release, delay gastric emptying and promote satiety, resulting in improved glycaemic control and clinically meaningful weight reduction. Agents within this class – including semaglutide, liraglutide, dulaglutide, exenatide and tirzepatide – have demonstrated reductions in glycated haemoglobin, body weight and major adverse cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Emerging evidence further highlights their role in hepatic steatosis improvement and cardiometabolic risk modification. Obesity is a well-established risk factor for chronic kidney disease (CKD), contributing through mechanisms such as glomerular hyperfiltration, renin–angiotensin–aldosterone system activation, lipotoxicity, hypertension and worsening proteinuria. Weight reduction has been associated with improvements in albuminuria and renal parameters, underscoring the therapeutic importance of metabolic optimisation in CKD populations. Beyond metabolic benefits, GLP-1 RAs have demonstrated significant renoprotective effects. Cardiovascular outcome trials – including LEADER, SUSTAIN-6 and REWIND – reported approximately a 21% relative risk reduction in composite renal outcomes, largely driven by decreased progression of albuminuria. The dedicated FLOW trial further confirmed a 24% reduction in major kidney disease events with semaglutide in patients with type 2 diabetes mellitus and CKD, establishing robust evidence for renal benefit on hard clinical endpoints. In patients with advanced CKD awaiting renal transplantation, obesity frequently limits transplant eligibility. GLP-1 RAs provide an effective pharmacologic strategy for weight reduction in this setting, facilitating achievement of institutional body mass index thresholds and potentially preserving residual renal function while on transplant waiting lists. Early observational studies suggest favourable safety and tolerability profiles in CKD stages 3–5 without increased risk of acute kidney injury. Post–renal transplantation, GLP-1 RAs have shown promise in managing new-onset manageable pharmacokinetic considerations with appropriate monitoring. Gastrointestinal adverse effects remain the most common limitation. This narrative review synthesises current evidence regarding the efficacy, safety and clinical applicability of GLP-1 RAs across the CKD spectrum – from pre-dialysis and dialysis populations to transplant candidates and recipients.