SGLT-2 inhibitors in heart failure: An updated systematic review and meta-analysis of 13 randomized clinical trials including 14618 patients with heart failure.

ABSTRACT Sodium-glucose co-transporter-2 (SGLT-2) inhibitors showed benefit in patients with heart failure. In this updated meta-analysis, we evaluate the therapeutic efficacy and safety of SGLT-2 inhibitors in heart failure patients. Different electronic databases were searched to find relevant articles. RevMan 5.4 was used for pooling data using a random/fixed-effect model, complemented by several sensitivity and subgroup analyses. A total of 13 randomized clinical trials including 14618 patients with heart failure were included in analysis among 6797 studies screened. The overall mortality rate was 12.45% in the SGLT-2 group and 14.67% among the placebo group with 18% lower odds of overall mortality (OR, 0.82; CI, 0.75-0.91) in the SGLT-2 group. Odds of cardiovascular mortality was 18% lower (OR, 0.82; CI, 0.74-0.92) in the SGLT-2 group. The odds of hospitalization for heart failure (HHF) was 38% lower during the study period (OR, 0.62; CI, 0.56-0.68) in the SGLT-2 group. Additionally, a benefit was seen for composite outcome HHF or mortality and considering subgrouping based on diabetes status, gender, and age groups. Though genital infection was significantly higher in the SGLT-2 group, the occurrence of severe adverse events, hypoglycemia, urinary tract infection, bone fracture, volume depletion, and other renal events did not differ between the two groups. Thus, SGLT-2 inhibitors improved cardiovascular outcomes among patients with heart failure with no significant difference in adverse events. Clinical benefit was comparable in diabetic and non-diabetic individuals, males and females, people in younger and older age groups with underlying heart failure, and HF with reduced ejection fraction.