Long-Term Cardiovascular Benefits Associated With Sodium-Glucose Cotransporter 2 Inhibitors

cardiovascular system
cardiovascular system
Use of sodium-glucose cotransporter inhibitors resulted in significant reductions in hemoglobin A1c, fasting blood glucose, and body weight.

The use of sodium-glucose cotransporter 2 (SGLT2) inhibitors is associated with significant cardiovascular and renal benefits as well as favorable long-term noncardiovascular safety, according to a meta-analysis published in Journal of the American Heart Association.

A meta-analysis of randomized controlled trials and adjusted observational studies was performed to evaluate cardiovascular outcomes associated with SGLT2 inhibitors. Studies included in this analysis featured a minimum duration of 26 weeks and 2000 patient-years of follow-up, whereas long-term noncardiovascular safety and efficacy outcomes were evaluated from studies featuring a minimum duration of 2 years and 1000 patient-years’ follow-up.

In the cardiovascular outcomes assessment, a total of 5 studies (n=351,476) were included. The use of SGLT2 inhibitors was associated with a significantly reduced risk for nonfatal myocardial infarction (hazard ratio [HR], 0.86; 95% CI, 0.76-0.98; P =.02), heart failure-related hospitalization (HR, 0.62; 95% CI, 0.55-0.69; P <.001), albuminuria progression (HR, 0.68; 95% CI, 0.58-0.81; P <.001), major adverse cardiac events (HR, 0.80; 95% CI, 0.69-0.92; P =.002), cardiovascular mortality (HR, 0.77; 95% CI, 0.60-0.98; P =.03), and all-cause mortality (HR, 0.67; 95% CI, 0.54-0.84; P <.001) when compared with placebo.

Overall, SGLT2 inhibitors did not provide a significant effect on reducing nonfatal stroke (HR, 0.96; 95% CI, 0.82-1.12; P =.67). A trial sequential analysis demonstrated an association between SGLT2 inhibitors and a 20% reduction in major adverse cardiac events.

Also, SGLT2 inhibitors were associated with reduced risk for hypoglycemia and acute kidney injury; however, an increased risk for urinary tract and genital infections was observed with therapy.

Researchers also found that SGLT2 inhibitors resulted in significant reductions in hemoglobin A1c levels (weighted mean difference [WMD], −0.39%; 95% CI, −0.52% to −0.26%), fasting blood glucose (WMD, −0.71 mmol/L; 95% CI, −0.88 to −0.55 mmol/L), and body weight (WMD, −2.90 kg; 95% CI, −3.72 to −2.07 kg) vs placebo.

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The investigators noted that they were unable to analyze patient-level data, which limits the findings to study-level data only. In addition, the findings may not be generalizable, as most of the trials included mainly white participants.

Findings from this analysis support the clinical use of SGLT2 inhibitors “either as alternative therapy or as adjuncts to metformin, other oral antiglycemic agents, or insulin.”


Zhang XL, Zhu QQ, Chen YH, et al. Cardiovascular safety, long-term noncardiovascular safety, and efficacy of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systemic review and meta-analysis with trial sequential analysis [published online January 20, 2018]. J Am Heart Assoc. doi:10.1161/JAHA.117.007165