Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access
Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc
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Review

Volume 12, Number 4, August 2021, pages 210-218


Update on the Cardiovascular Benefits of Sodium-Glucose Co-Transporter-2 Inhibitors: Mechanism of Action, Available Agents and Comprehensive Review of Literature

Table

Table 1. A Summary for SGLT2 Inhibitors Clinical Trials Including the Studied Drug, Primary Outcome, NNT for the Primary Outcome, and the Reported Adverse Events in Each Trial
 
Trial nameSGLT2 inhibitorPrimary outcome measureNNT for the primary outcomeAdverse events
SGLT2: sodium-glucose co-transporter-2; NNT: number needed to treat; MI: myocardial infarction; UTI: urinary tract infection; ESRD: end-stage renal disease; DKA: diabetic ketoacidosis; MACE: major adverse cardiovascular event; HF: heart failure; MRI: magnetic resonance imaging; NT-proBNP: N-terminal pro-B-type natriuretic peptide; KCCQ: Kansas City Cardiomyopathy Questionnaire; LVESV: left ventricular end-systolic volume.
1. EMPA-REG OUTCOMEEmpagliflozin 10 and 25 mgA composite of cardiovascular death, nonfatal MI (excluding silent MI), or nonfatal strokesNNT = 63/3.1 years or NNT = 195/1 yearGenital infections, and urosepsis without an increase in the overall rate of UTI, complicated UTI or pyelonephritis)
2. CANVASCanagliflozin 100 and 300 mgA composite cardiovascular deaths, nonfatal MI, or nonfatal strokesNNT = 220/1 yearGenital infections, increased rate of amputation, and increased bone fracture (statistically insignificant)
3. CREDENCECanagliflozin 100 mgA composite of ESRD, serum creatinine baseline doubling, or renal and cardiovascular deathsNNT = 22/2.5 yearsDKA
4. DECLARE-TIMI 58Dapagliflozin 10 mgMACE for safety; MACE and cardiovascular death or HF hospitalization for efficacyNot superior for safety, however, NNT = 112/4.2 years or NNT = 470/1 year for efficacyGenital infections and DKA
5. VERTIS-CVErtugliflozin 5 and 15 mgMACEN/A as there was no difference in risk reductionGenital infections and UTI (statistically significant), with more DKA and amputation events in the ertugliflozin arms
6. EMPA-HEARTEmpagliflozin 10 mgThe delta in left ventricular mass index as noted on cardiac MRIN/AN/A
7. DEFINE-HFDapagliflozin 10 mgDifference in mean NT-proBNP; improvement of ≥ 5 points in the KCCQ or a ≥ 20% decrease in NT-proBNPN/AN/A
8. PRESERVED-HFDapagliflozin 10 mgSymptomatic and physical limitations as measured by the KCCQN/AN/A
9. DAPA-HFDapagliflozin 10 mgDeaths from cardiovascular causes, HF hospitalization, or urgent HF visitNNT = 20.4/18 monthsNo statistically significant difference in adverse events
10. EMPEROR-REDUCEDEmpagliflozin 10 mgCardiovascular death or HF hospitalizationNNT = 19/1.3 yearsUncomplicated genital tract infection
11. EMPEROR-PRESERVEDEmpagliflozin 10 mgTime-to-first-event analysis of the combined risk for cardiovascular death and HF hospitalizationStudy is not completed yetStudy is not completed yet
12. EMBRACE-HFEmpagliflozin 10 mgThe delta change in pulmonary artery pressure from baseline to end of treatmentN/AN/A
13. REFORMDapagliflozin 10 mgThe difference in LVESV using cardiac MRIN/ADecline in renal function, which was transient and resolved after reduction of loop diuretic dose without dapagliflozin dose change
14. EMPAEmpagliflozin 10 mgDetermining if empagliflozin would improve the loop diuretic’s natriuretic effectN/ANot reported
15. SOLOIST-WHFSotagliflozin 400 mg titrated from 200 mg if no side effectsCardiovascular death, HF hospitalizations, and urgent HF visitsNNT = 7/9 monthsDiarrhea, genital fungal infections, and severe hypoglycemia