Update on the Efficacy and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Chronic Diseases: A Systematic Review and Meta-Analysis

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have emerged as vital medications for the management of type 2 diabetes mellitus (T2DM). Numerous studies have highlighted the cardioprotective and renal protective benefits of SGLT2 inhibitors. Consequently, it is essential to assess their efficacy and safety in patients with chronic diseases. Method: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the effects of SGLT2 inhibitors on major cardiovascular and safety outcomes in patients with T2DM, heart failure (HF), and chronic kidney disease (CKD). We searched the PubMed, Cochrane, and Embase databases for trials published between 30 September 2021 and 17 May 2023. The primary outcomes of interest included nonfatal myocardial infarction (MI), hospitalization for heart failure (HHF), cardiovascular death, and nonfatal stroke. The safety outcomes assessed were hypoglycemia, urinary tract infections (UTIs), and acute kidney injury (AKI). Result: We identified 13 RCTs involving 90,413 participants. In patients with T2DM, SGLT2 inhibitors significantly reduced the risk of nonfatal MI by 12% (hazard ratio [HR] = 0.88, 95% confidence interval [CI]: 0.78-0.98), HHF by 33% (HR = 0.67, 95% CI: 0.62-0.74), and cardiac death by 15% (HR = 0.95, 95% CI: 0.80-1.13). However, they did not significantly reduce the risk of nonfatal stroke (HR = 0.85, 95% CI: 0.75-0.95). In patients with HF, SGLT2 inhibitors reduced the risk of HHF by 28% (HR = 0.72, 95% CI: 0.66-0.77) and cardiac death by 12% (HR = 0.88, 95% CI: 0.80-0.96). For patients with CKD, SGLT2 inhibitors reduced the risk of HHF by 35% (HR = 0.65, 95% CI: 0.55-0.76) and cardiac death by 16% (HR = 0.84, 95% CI: 0.73-0.96). Regarding safety outcomes, SGLT2 inhibitors did not significantly increase the risk of hypoglycemia in patients with T2DM, HF, or CKD, nor did they increase the risk of urinary tract infections (UTIs) in patients with HF or CKD, or the risk of acute kidney injury (AKI) in patients with HF. However, they did increase the risk of UTIs by 8% (risk ratio [RR] = 1.08, 95% CI: 1.01-1.16) in patients with T2DM and reduced the risk of AKI by 22% (RR = 0.78, 95% CI: 0.67-0.89) and 19% (RR = 0.81, 95% CI: 0.69-0.97) in patients with T2DM and CKD, respectively. Conclusions: SGLT2 inhibitors have demonstrated a significant improvement in cardiovascular outcomes for patients with T2DM, HF, and CKD while also maintaining a favorable safety profile. These findings advocate for the broader application of SGLT2 inhibitors in the management of chronic diseases, particularly in reducing the incidence of nonfatal MI, HHF, and cardiac death. Further research is essential to optimize their use across diverse patient populations and stages of disease.