The risk of all-cause death with dapagliflozin versus placebo: a systematic review and meta-analysis of phase III randomized controlled trials

ABSTRACT

Background

Dapagliflozin has proven cardioprotective and nephroprotective effects. However, the risk of all-cause death with dapagliflozin remains unclear.

Research design and methods

We performed a meta-analysis of phase III randomized controlled trials (RCTs) for the risk of all-cause death and safety events with dapagliflozin compared to placebo. PubMed and EMBASE were searched from inception to 20 September 2022.

Results

Five trials were included in the final analysis. Compared with the placebo, dapagliflozin demonstrated an 11.2% reduction in the risk of all-cause death (OR 0.88, 95% CI 0.81–0.94). No statistically significant difference in urinary tract infection (OR: 0.95, 95% CI: 0.78 to 1.17), bone fracture (OR: 1.06, 95% CI: 0.94 to 1.20), and amputation (OR: 1.01, 95% CI: 0.82 to 1.23) was observed between patients treated with dapagliflozin and placebo. Compared with placebo, dapagliflozin was associated with a significant reduction in acute kidney injury (OR: 0.71, 95% CI: 0.60 to 0.83), and increased the risk of genital infection (OR: 8.21, 95% CI: 4.19 to 16.12).

Conclusions

Dapagliflozin was associated with significantly reduced all-cause death and increased genital infection. Dapagliflozin was safe concerning urinary tract infection, bone fracture, amputation, and acute kidney injury, compared with the placebo.

KEYWORDS:

• SGLT2 inhibitors
• dapagliflozin
• all-cause death
• urinary tract infection

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

HB Chen conceived the research idea and drafted the manuscript, HB Chen and RS Meng performed study selection, YL Yang and TH Yu extracted data from all included studies, and RS Meng performed the statistical analysis.

Data availability statement

All the original data supporting the findings of this study are available in the supplementary appendixes of this paper.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2182290

Additional information

Funding

This paper was not funded.