Comparative safety of sodium-glucose co-transporter 2 inhibitors in elderly patients with type 2 diabetes mellitus and diabetic kidney disease: a systematic review and meta-analysis

The safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors in elderly patients with diabetic kidney disease (DKD) is still controversial. This study aimed to analyze the safety of SGLT2 inhibitors in elderly patients with type 2 diabetes mellitus (T2DM) and DKD. We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to March 2023. Randomized controlled trials (RCTs) were included. Data including patient characteristics and interesting outcomes were extracted, and the dichotomous data and continuous variables were evaluated using risk ratio (RR) with 95% confidence intervals (CIs) and mean difference (MD) with 95% CIs, respectively. A total of 14 RCTs with 59874 participants were finally included. There were 38,252 males (63.9%) and 21,622 females (36.1%). The patients' mean age was > 64.6 years. SGLT2 inhibitors could delay the further decline of estimated glomerular filtration rate (eGFR) when eGFR >= 60 ml/min/1.73m(2) (MD: 2.36; 95%CI [1.15-3.57]). SGLT2 inhibitors in elderly patients with eGFR < 60 ml/min/1.73m(2) (RR: 0.86; 95%CI [0.67-1.11]) may have a relatively increased risk of acute kidney injury compared to eGFR >= 60 ml/min/1.73m(2). SGLT2 inhibitors increased the incidence of genital mycotic infections (RR: 3.47; 95%CI [2.97-4.04]) and diabetic ketoacidosis (RR: 2.25; 95%CI [1.57-3.24]). Except for genital mycotic infections and diabetic ketoacidosis, other adverse reactions were few, indicating that SGLT2 inhibitors are relatively safe for elderly patients with T2DM and DKD. Safety and renoprotection may be diminished when SGLT2 inhibitors are used in elderly patients with eGFR < 60 ml/min/1.73m(2).