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Recently, Lin and colleagues assessed the safety of sodium-glucose cotransporter 2 inhibitors (SGLT2is) by a meta-analysis [1], in which the authors assessed 16 kinds of adverse events (AE) reported in the published articles based on 10 randomized controlled trials. We conducted a further meta-analysis and targeted the association between use of SGLT2is and occurrences of various kinds of serious AE published in the Clinical Trials website (clinicaltrials.gov). Our meta-analysis revealed that use of SGLT2is was not significantly associated with occurrences of 980 kinds of serious AE but was significantly associated with lower risks of 29 kinds of serious AE, especially including several important respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease, sleep apnoea syndrome, and pneumonia). These findings may cause more studies to evaluate the possibilities of gliflozins being used for prevention of these specific diseases.

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The cardiorenal benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) are established, whereas those in patients without T2DM are not established. We sought to assess the cardiorenal efficacy and safety of SGLT2 inhibitors in non-T2DM patients by performing a meta-analysis based on the subgroup data of non-T2DM patients from relevant secondary analysis articles in which subgroup analyses were done according to the status of diabetes. Compared to placebo, SGLT2 inhibitors significantly reduced heart failure hospitalization [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.59–0.83] and kidney-specific composite outcome (RR 0.55, 95% CI 0.40–0.75) and increased Kansas City Cardiomyopathy Questionnaire total score by 1.15 (95% CI 1.05–1.25) in patients without T2DM with heart failure (HF) or chronic kidney disease (CKD), whereas gliflozins did not significantly affect cardiovascular death, all-cause mortality, volume depletion, fracture, and amputation in this vulnerable population. There was no event of major hypoglycemia or diabetic ketoacidosis observed in the non-T2DM subgroup in included trials. These findings will further prompt gliflozins to be used for the prevention of HF and renal failure events and for the improvement of life quality in patients without T2DM with HF or CKD.

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