SGLT2 Inhibitors in Elderly Patients: Clinical Perspectives from Metabolic and Cardiorenal Protection to Implementation

Figures

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  Figure 1. PRISMA flow diagram of study selection. The diagram illustrates the process of study identification, screening, eligibility assessment, and inclusion in this systematic review. A total of 2488 records were identified through database searching, with no duplicates removed. After title and abstract screening, 2441 records were excluded. Overall, 47 full-text articles were assessed for eligibility, of which 37 were excluded due to lack of age-specific data, absence of relevant CV or renal outcomes, non-original study design, or insufficient full-text availability. Ultimately, 10 studies were included in the qualitative synthesis.

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  Figure 2. Cardiorenal and systemic mechanisms of SGLT2 inhibition. Sodium–glucose co-transporter-2 (SGLT2) inhibitors induce glycosuria and natriuresis, generating an “energy–sodium drain” that contributes to coordinated cardiovascular, renal, and vascular benefits. At the cardiac level, mild osmotic diuresis and reduced intracellular sodium, partly mediated by inhibition of the Na+/H+ exchanger, promote hemodynamic unloading and improve myocardial energetics by enhancing mitochondrial efficiency. In the kidney, restoration of tubuloglomerular feedback reduces intraglomerular pressure, attenuates hyperfiltration, and limits albuminuria, thereby protecting against progressive renal injury. Systemically, SGLT2 inhibition is associated with reductions in oxidative stress and uric acid levels, improved endothelial function, and modest decreases in arterial stiffness and blood pressure, contributing to overall CV and renal protection.

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  Figure 3. Endpoint-specific cardiovascular and renal effects of SGLT2 inhibitors across the cardiorenal continuum. The symbol “↓” indicates a reduction/decrease.

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  Figure 4. GLT2 inhibitors as a counterbalancing mechanism in cardiometabolic ageing.

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  Figure 5. Practical algorithm for the initiation and monitoring of SGLT2 inhibitors across cardiometabolic phenotypes. This figure illustrates a pragmatic framework for the safe initiation and clinical management of SGLT2i inhibitors in patients with cardiometabolic diseases. The algorithm is structured into three sequential phases. In the “Select and Start” phase, clinicians identify appropriate candidates, including patients with T2DM, HF, or CKD, verify renal eligibility according to the approved indication and the specific SGLT2 inhibitor, while also assessing volume status, frailty, nutritional reserve, and concomitant diuretic therapy. The “Pause and Adjust” phase highlights situations requiring caution or dose adjustment, such as concomitant loop diuretic therapy, low systolic blood pressure, or the expected transient decline in estimated glomerular filtration rate during the first weeks of treatment. The “Stop and Educate” phase emphasises temporary treatment interruption during acute illness or severe dehydration, as well as the importance of patient education, including sick-day rules and genital hygiene. The lower matrix integrates these principles into a phenotype-oriented…