Current Drug Therapy

The role of SGLT-2 inhibitors in managing type 2 diabetes

Yumiko Tsushima, MD, M. Cecilia Lansang, MD, MPH and Vinni Makin, MBBS, MD, FACE
Cleveland Clinic Journal of Medicine January 2021, 88 (1) 47-58; DOI: https://doi.org/10.3949/ccjm.88a.20088

Article Figures & Data

Tables

  • TABLE 1

    Absolute change in hemoglobin A1c with SGLT-2 inhibitor monotherapy compared with placebo

    EmpagliflozinaCanagliflozinbDapagliflozincErtugloflozind
    Low doseHigh doseLow doseHigh doseLow doseHigh doseLow doseHigh dose
    −0.74%−0.85%−0.90%−1.20%−0.54%−0.60%−0.50%−0.50%

    • ↵a Empagliflozin low dose = 10 mg, high dose = 25 mg.6

    • ↵b Canagliflozin low dose = 100 mg, high dose = 300 mg.5

    • ↵c Dapagliflozin low dose = 5 mg, high dose = 10 mg.7

    • ↵d Ertugloflozin low dose = 5 mg, high dose = 15 mg.8

  • TABLE 2

    Cardiovascular outcomes in 4 major trials of SGLT-2 inhibitors

    EMPA-REG OUTCOME21CANVAS22DECLARE-TIMI 5823VERTIS-CV24
    PopulationType 2 diabetes + cardiovascular diseaseType 2 diabetes + cardiovascular disease or multiple risk factors for itType 2 diabetes + cardiovascular disease or multiple risk factors for itType 2 diabetes + cardiovascular disease
    Number of patients7,02010,14217,1608,246
    History of cardiovascular disease99%65.6%40.6%100%
    History of heart failure10.1%14.4%10.2%23.7%
    Outcomes with SGLT-2 inhibitor
    MACE (relative risk reduction)14%14%Not significantNot significant
    MACE (number needed to treat)63217Not availableNot available
    Cardiovascular death (relative risk reduction)38% NotsignificantNot significantNot significant
    Hospitalization for heart failure (relative risk reduction)35%35%27%30%
    Hospitalization for heart failure (number needed to treat)7131212591

    • CANVAS = Canagliflozin Cardiovascular Assessment Study; DECLARE-TIMI 58 = Dapagliflozin Effect on Cardiovascular Events; EMPA-REG OUTCOME = Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; MACE = major atherosclerotic cardiovascular events; VERTIS CV = Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes

  • TABLE 3

    Risks and benefits of SGLT-2 inhibitors

    BenefitsRisks
    Hemoglobin A1cWeight and blood pressureHeart failure hospitalizationsCardiovascular eventsProgression of renal diseaseFracture, amputationGenital infection
    EmpagliflozinDecreaseDecreaseDecreaseDecreaseDecreaseNo changeIncrease
    CanagliflozinDecreaseDecreaseDecreaseNo changeDecreaseNo changeaIncrease
    DapagliflozinDecreaseDecreaseDecreaseNo changeDecreaseNo changeIncrease
    ErtugliflozinDecreaseDecreaseDecreaseNo changeNo changeNo changeIncrease

    • ↵a Changed from “increases risk” to “no change” after the removal of the black box warning by the US Food and Drug Administration.

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