Aronow WS, et al. - A comparative scrutiny was pursued of the effectiveness of empagliflozin on the mortality and cardiovascular morbidity in type 2 diabetes. A reduction was noted in the all-cause and cardiovascular mortality due to empagliflozin in patients with established cardiovascular disease and type 2 diabetes. The sparse direct evidence did not reveal any variation between empagliflozin and metformin, glimepiride, linagliptin, or sitagliptin in terms of mortality. Long-term comparative safety was yet to be established.

Methods

• Random-effects direct frequentist meta-analyses were performed of the aggregate data and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.
• Data search was carried out of the PubMed, EMBASE, the Cochrane Library, clinicaltrials.gov, and PharmaPendium up to May 2017.
• Researchers selected 11 meta-analyses, multiple publications, and unpublished data from 29 randomized controlled trials (RCTs).

Results

• A reduction was noted all-cause mortality [relative risk (RR) of death, 0.69; 95% confidence interval (CI): 0.58-0.82; number needed to treat (NNT) to postpone mortality in one patient, 39; 95% CI: 26-79; 1 RCT of 7,020 patients) due to empagliflozin, in patients with but not without (RR, 0.90; 95% CI: 0.36-2.23; 14 RCTs of 7,707 patients) established cardiovascular disease when compared with placebo.
• It also caused a reduction in the cardiovascular mortality (RR, 0.62; 95% CI: 0.50-0.78; NNT, 45; 95% CI: 30-90; 1 RCT of 7,020 patients) in patients with but not without (RR, 0.98; 95% CI: 0.29-3.33; 10 RCTs of 5,429 patients) established cardiovascular disease when compared with placebo.
• No variations were reported in the cardiovascular morbidity and mortality and all-cause mortality between empagliflozin and metformin (4 RCTs of 1,344 patients), glimepiride (1 RCT of 1,549 patients), linagliptin (2 RCTs of 1,348 patients), or sitagliptin (3 RCTs of 1,483 patients).
• Sodium-glucose cotransporter 2 (SGLT2) inhibitors, mostly due to empagliflozin, led to a decrease all-cause and cardiovascular mortality, as revealed by two network meta-analyses.
• However, these increased the risk of nonfatal stroke, genital infection, and volume depletion.