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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
Yumiko Tsushima
Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic
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M. Cecilia Lansang
Director, Main Campus Department of Endocrinology, Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic; Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH
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Vinni Makin
Director, East Region, Department of Endocrinology Diabetes, and Metabolism, Cleveland Clinic; Assistant Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH
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  • For correspondence: makinv@ccf.org
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    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

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    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

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    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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Cleveland Clinic Journal of Medicine: 88 (1)
Cleveland Clinic Journal of Medicine
Vol. 88, Issue 1
1 Jan 2021
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The role of SGLT-2 inhibitors in managing type 2 diabetes
Yumiko Tsushima, M. Cecilia Lansang, Vinni Makin
Cleveland Clinic Journal of Medicine Jan 2021, 88 (1) 47-58; DOI: 10.3949/ccjm.88a.20088

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The role of SGLT-2 inhibitors in managing type 2 diabetes
Yumiko Tsushima, M. Cecilia Lansang, Vinni Makin
Cleveland Clinic Journal of Medicine Jan 2021, 88 (1) 47-58; DOI: 10.3949/ccjm.88a.20088
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  • Article
    • ABSTRACT
    • SODIUM-GLUCOSE COTRANSPORTER-2
    • EFFECT ON GLYCEMIC CONTROL
    • EFFECT ON CARDIOVASCULAR OUTCOMES
    • POSSIBLE MECHANISMS OF CARDIOVASCULAR BENEFIT
    • EFFECT ON RENAL OUTCOMES
    • MECHANISM OF RENAL PROTECTION
    • EFFECT ON METABOLIC OUTCOMES
    • STUDIES IN NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)
    • ADVERSE EFFECTS OF SGLT-2 INHIBITORS
    • REVIEW OF THE GUIDELINES
    • FUTURE DIRECTIONS
    • DISCLOSURES
    • REFERENCES
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