The role of combining exercise with pharmacologic management of CKD: From SGLT2 and GLP-1 to broader therapeutic strategies.

Abstract

Given the exceptional evolution of pharmacological approaches to chronic kidney disease (CKD) management and their potential interactions with lifestyle, in this review, we describe the intersection of exercise and pharmacotherapy, and the possible role of exercise training as an adjunct management option to optimise glucose-lowering therapies (GLTs) in people living with diabetes and CKD. Exercise remains a cornerstone intervention for individuals living with CKD and diabetes, providing well-established benefits for cardiovascular health, metabolic regulation, and preservation of physical function. While GLTs, including sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs), offer significant promise, these pharmacologic advances must be contextualised within a broader lifestyle framework to achieve optimal outcomes. Exercise and GLTs share complementary mechanisms, such as improvements in insulin sensitivity, inflammation, and body composition. Yet, the synergistic potential of combining these interventions warrants further investigation through high-quality trials and mechanistic studies. Current evidence is encouraging but insufficient to confidently guide clinical practice. Future research should prioritise strategies that integrate pharmacotherapy with structured exercise programs, while accounting for patient-specific factors such as comorbidities, frailty, and functional limitations. Implementation science will be critical to translate these findings into routine care, leveraging multidisciplinary teams, digital health tools, and behavioural support. Ultimately, success will depend on integrative, person-centred care models that align pharmacologic and lifestyle interventions to enhance quality of life, reduce disease burden, and improve long-term outcomes for people with CKD and diabetes.