Risk: Benefit Profile of Sodium-Glucose Cotransporter 2 Inhibitors: JCEM
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are first-line antidiabetic agents with demonstrated cardiovascular benefits. In a recent meta-analysis, researchers have reported that SGLT2 inhibitors are safe but increase the risk of infections and ketoacidosis and decrease the risk of Acute Kidney Injury (AKI). The study findings were published in The Journal of Clinical Endocrinology & Metabolism on April 25, 2021.
Prior meta-analyses have examined AEs associated with these drugs in general, but such knowledge needs to be updated with the results of more recent trials. In addition, the occurrence of various AEs with different underlying diseases is unknown. Therefore, researchers of the National Taiwan University Hospital conducted a study to investigate the occurrence of various adverse events (AEs) associated with sodium-glucose cotransporter 2 inhibitors (SGLT2i). They further examined the level of risk of AEs in patients with different underlying diseases.
It was a quantitative meta-analysis of randomized controlled trials (RCTs) retrieved from the MEDLINE and EMBASE databases and the Cochrane library and included 71,553 participants. The outcomes assessed were 4 overall safety outcomes (AEs) and 12 specified safety outcomes. They also performed further analyses on various subgroups, which were defined based on the status of diabetes mellitus (DM), atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease, and congestive heart failure, and by the dosage of SGLT2i (high dose versus low dose).
Key findings of the study were:
- Upon analysis, the researchers found that SGLT2i led to increased risks of a genital infection (risk ratio [RR] 3.56), urinary tract infection (RR 1.06), diabetic ketoacidosis (RR 2.23), and volume depletion (RR 1.14).
- They also found that the use of SGLT2i was associated with reduced risks of any serious AE (RR 0.92), acute kidney injury (AKI) (RR 0.84), and hyperkalemia (RR 0.84).
- In a subgroup analysis, they noted that the risk of amputation was higher in patients with ASCVD than in those without ASCVD (RR 1.44 vs 0.96).
The authors concluded, "The use of SGLT2i is generally safe. SGLT2i may be associated with increased risks of genital infection but is protective against AKI. Of note, the risk of amputation was higher in patients with ASCVD."
They further noted, "The key to the safe use of SGLT2i lies in the identification of high-risk populations and close surveillance of patients after treatment."
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