Anna Kochanowska

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have proven their favorable cardiovascular and nephroprotective benefits in large randomized-controlled trials (RCTs). Given that older adults constitute a substantial part of patients with type 2 diabetes mellitus (T2DM), heart failure (HF), and chronic kidney disease (CKD), they are the primary target population for SGLT2 inhibitor therapy. However, their representation in clinical trials remains low and it does not reflect the real-life heterogeneity of this group of patients. As chronological age alone does not adequately reflect the biological age, it is important to evaluate older adults using a multidimensional approach, particularly with regard to frailty. This review aims to summarize and critically appraise the available evidence regarding the efficacy of SGLT2 inhibitors in older and frail adults, with a focus on age-specific outcomes, such as cognitive outcomes, risk of sarcopenia, functional activity and current gaps in evidence related to frailty.

Sodium–glucose cotransporter 2 inhibitors (SGLT2is) are glucose-lowering agents whose positive impact on cardiovascular risk has been described extensively. Not only do they influence lipid profile, blood pressure, atherosclerosis risk, hemoglobin level, and insulin resistance, but they also reduce cardiovascular events, all-cause mortality, and hospitalization rates. Some of these effects may be due to their impact on serum uric acid (SUA) concentration. Findings from nine meta-analyses showed that, indeed, SGLT2is significantly reduce SUA. The data on the drug- and dose-dependency of this effect were inconclusive. Several factors alternating the beneficial effects of SGLT2is on SUA, such as glycated hemoglobin concentration (HbA1c), presence of diabetes, and baseline SUA level, were described. Even though there is a consensus that the lowering of SUA by SGLT2is might be due to the increased urinary excretion rate of uric acid (UEUA) rather than its altered metabolism, the exact mechanism remains unknown. The influence of SGLT2is on SUA may not only be used in gout treatment but may also be of huge importance in explaining the observed pleiotropic effects of SGLT2is.

Coronary artery disease (CAD) is the leading cause of death worldwide. Patients with pre-existing CAD were shown to have a more severe course of COVID-19, but this association has not been clarified. We performed a meta-analysis to determine the association between CAD and COVID-19 outcomes. We searched Scopus, Medline (PubMed), Web of Science, Embase, and Cochrane databases up to 2 November 2021. There were 62 studies with a total population of 49,286 patients included in the meta-analysis. CAD occurrence in survivor vs. non-survivor groups varied and amounted to 9.2% vs. 22.9%, respectively (OR = 0.33; 95%CI: 0.29 to 0.39; I² = 70%; p < 0.001). CAD was also associated with increased severity of COVID-19 disease and was (10.8% vs. 5.6%, respectively, for severe vs. non-severe groups (OR = 2.28; 95%CI: 1.59 to 3.27; I² = 72%; p < 0.001). The role of history of CAD in mortality and severe condition in COVID-19 presents itself as prominent—although a risk of bias in retrospective trials needs to be assessed, in case of our meta-analysis the statistically significant results when it comes to higher mortality among patients with CAD compared to non-CAD patients, a more severe condition observed in patients with CAD, and a visibly more frequent admission to intensive care unit in patients with CAD, it seems that an incidence of cardiovascular events plays a role in COVID-19 prognosis.