Safety outcomes reported in landmark randomized controlled trials of SGLT2 inhibitors.
Study
Important safety findings
Clinical interpretation
EMPA-KIDNEY
Serious adverse events, acute kidney injury, dehydration, hyperkalemia, urinary tract infection, and fracture occurred at similar rates between treatment groups.
Supported the safety of empagliflozin across a broad CKD population.
DAPA-CKD
No cases of diabetic ketoacidosis with dapagliflozin; rates of amputation and fracture were similar between treatment groups.
Demonstrated an acceptable safety profile even among patients with advanced CKD and those without diabetes.
CREDENCE
No significant increase in amputation or fracture compared with placebo.
Provided reassurance regarding the safety of canagliflozin in patients with diabetic CKD.
EMPA-REG OUTCOME
Increased incidence of genital infections; no increase in hypoglycemia, acute kidney injury, diabetic ketoacidosis, fracture, or volume depletion.
Empagliflozin demonstrated a favorable overall safety profile, with genital mycotic infections representing the most consistent adverse event.
CANVAS Program
Increased risk of lower-limb amputation; small number of diabetic ketoacidosis events; increased fracture risk reported in CANVAS but not consistently across CANVAS-R.
Although an amputation signal was observed, subsequent trials did not consistently reproduce this finding, suggesting that the overall cardiorenal benefits should be weighed against individual patient risk factors.
DECLARE-TIMI 58
Higher incidence of diabetic ketoacidosis and serious genital infections leading to treatment discontinuation compared with placebo.
Serious adverse events remained uncommon, and the overall safety profile was considered acceptable.
SGLT2: sodium-glucose cotransporter-2; CKD: chronic kidney disease. Summary of the principal safety findings reported in the landmark randomized controlled trials evaluating SGLT2 inhibitors in chronic kidney disease and type 2 diabetes. References: [1–6].
The authors declare that they have no conflicts of interest.
Ethical approval
Not applicable.
Consent to participate
Not applicable.
Consent to publication
Not applicable.
Availability of data and materials
The data supporting the findings of this study are derived from publicly available published articles included in this systematic review. Additional data extracted and analyzed during the current study are available from the corresponding author upon reasonable request.
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References
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