Efficacy and safety profile of SGLT2 inhibitors in the elderly: How is the benefit/risk balance?

Type 2 diabetes mellitus (T2DM) is a highly prevalent health condition in the aging population. Older adults with T2DM have higher risks of cardiovascular disease, heart failure (long underestimated) and premature death than those without diabetes. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have proven their ability to improve cardiovascular prognosis and reduce the risk of hospitalization for heart failure (hHF). However, several adverse events have been reported, whose incidence and severity might be increased in the elderly population. The aims of this comprehensive review were to analyze the benefit-risk ratio of SGLT2i therapy in older patients with T2DM by collecting data from (i) large prospective placebo-controlled cardiovascular outcome trials (including those dedicated to heart failure), using both original publications and dedicated post-hoc analyses across different age groups and (ii) observational cohort studies, describing the effects of SGLT2is versus other glucose-lowering agents on cardiovascular outcomes and hHF in elderly patients or these effects in different age groups. Overall, consistent results showed a similar relative risk reduction in cardiovascular mortality and hHF with SGLT2is independently of age. The absolute risk reduction may be greater in elderly because of a higher background risk in older versus younger patients. Similarly, the safety profile of SGLT2is appeared comparable in older versus younger patients. In conclusion, the benefit/risk balance favors the use of SGLT2is in older patients at risk of cardiovascular disease and/or heart failure. Caution may be required in very old frail patients, especially those exposed to an increased risk of volume depletion.