Sodium-glucose co-transporter 2 inhibitors: A review of their use in older people with type 2 diabetes mellitus

Traditional treatment options for type 2 diabetes mellitus (T2DM) target the primary pathophysiological defects of increased insulin resistance, hepatic glucose overproduction and progressive pancreatic beta-cell dysfunction. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are the newest class of medication for T2DM and provide an alternative, insulin-independent, pathway for addressing hyperglycaemia, by reducing renal glucose reabsorption. SGLT2 inhibitors are associated with a low risk of hypoglycaemia and recent trials have indicated, for empagliflozin at least, reductions in cardiovascular morbidity and mortality and a slower progression of kidney disease. These characteristics make SGLT2 inhibitors attractive second-line agents. Adverse effects include an increased risk of genitourinary tract infections, hypotension, fractures and acute renal impairment. Common events in hospitalised older patients, such as volume depletion, indwelling catheter use, potential renal insults (e.g. aminoglycosides or intravenous contrast administration) and unpredictable haemodynamics, may exacerbate these adverse effects, suggesting SGLT2 inhibitors may be best avoided in this setting. Clinical heterogeneity of the older patient cohort calls for individualised management. As there is a lack of evidence to guide diabetes management in older people, this review aims to summarise the available evidence from clinical trials and meta-analyses and provide a practical perspective on how best to use SGLT2 inhibitors in older patients.