Department of Internal Medicine, Jeju National University College of Medicine, Jeju, Korea
Copyright © 2024 Korean Diabetes Association
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CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
Trial |
Agent |
|||||
---|---|---|---|---|---|---|
Empagliflozin |
Canagliflozin |
Dapagliflozin |
Ertugliflozin |
Sotagliflozin |
||
EMPA-REG OUTCOME [4] | CANVAS [5] | CREDENCE [6] | DECLARE-TIMI 58 [7] | VERTIS-CV [8] | SCORED [9] | |
3-P MACEa | 0.86 (0.74–0.99) | 0.86 (0.75–0.97) | 0.80 (0.67–0.95) | 0.93 (0.84–1.03) | 0.97 (0.85–1.11) | 0.84 (0.72–0.99) |
Non-fatal MI | 0.87 (0.70–1.09) | 0.90 (0.71–1.15) | NA | 1.01 (0.84–1.21) | 1.00 (0.76–1.32) | 0.68 (0.52–0.89) |
Non-fatal stroke | 1.24 (0.92–1.67) | 0.85 (0.69–1.05) | NA | 0.89 (0.77–1.01) | 1.00 (0.86–1.27) | 0.66 (0.48–0.91) |
CV death | 0.62 (0.49–0.77) | 0.87 (0.72−1.06) | 0.78 (0.61−1.00) | 0.98 (0.82−1.17) | 0.92 (0.77–1.11) | 0.90 (0.73–1.12) |
HHF | 0.65 (0.50–0.85) | 0.67 (0.52–0.87) | 0.61 (0.47–0.80) | 0.73 (0.61–0.88) | 0.70 (0.54–0.90) | 0.67 (0.55–0.82) |
Renal composite outcomeb | 0.54 (0.40–0.75) | 0.60 (0.47–0.77) | 0.70 (0.59–0.82) | 0.53 (0.43–0.66) | 0.81 (0.64–1.03) | 0.71 (0.46–1.08) |
HR, hazard ratio; CI, confidence interval; CVOT, cardiovascular outcome trial; SGLT2i, sodium-glucose cotransporter 2 inhibitor; EMPA-REG OUTCOME, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; CANVAS, Canagliflozin Cardiovascular Assessment Study; CREDENCE, Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation; DECLARETIMI 58, Dapagliflozin Effect on Cardiovascular Events-Thrombolysis In Myocardial Infarction 58; VERTIS-CV, Evaluation of Ertugliflozin EffIcacy and Safety Cardiovascular Outcomes Trial; SCORED, Effect of Sotagliflozin on Cardiovascular and Renal Events in Participants With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk; 3-P MACE, 3-point major adverse cardiovascular events; MI, myocardial infarction; NA, not available; CV, cardiovascular; HHF, hospitalization for heart failure.
a 3-P MACE: a composite of death from CV causes, nonfatal MI, or nonfatal stroke,
b The definition varies according to the trial. EMPA-REG OUTCOME, CANVAS, and DECLARE-TIMI 58: ≥40% decrease in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2, end-stage renal disease, or death from renal cause; CREDENCE: doubling of serum creatinine level, end-stage kidney disease, renal death or CV death; VERTIS-CV: doubling of serum creatinine level, end-stage kidney disease, renal death; SCORED: ≥50% decrease in the eGFR from baseline for ≥30 days, long-term dialysis, renal transplantation, or sustained eGFR of <15 mL/min/1.73 m2 for ≥30 days.
Agent |
Lixisenatide |
Liraglutide |
Semaglutide |
Exenatide QW |
Albigutide |
Dulaglutide |
Oral Semaglutide |
Efpeglenatide |
ITCA 650 (Exenatide) |
---|---|---|---|---|---|---|---|---|---|
Trial | ELIXA [10] | LEADER [11] | SUSTAIN 6 [12] | EXSCEL [13] | HARMONY [14] | REWIND [15] | PIONEER 6 [16] | AMPLITUDE-O [17] | FREEDOM-CVO [18] |
3-P MACEa | 1.02 (0.89–1.17) | 0.87 (0.78–0.97) | 0.74 (0.58–0.95) | 0.91 (0.83–1.00) | 0.78 (0.68–0.90) | 0.88 (0.79–0.99) | 0.79 (0.57–1.11) | 0.73 (0.58–0.92) | 1.24 (0.90–1.70) |
Non-fatal MI | 1.03 (0.87–1.22) | 0.88 (0.75–1.03) | 0.74 (0.51–1.08) | 0.97 (0.85–1.10) | 0.75 (0.61–0.90) | 0.96 (0.79–1.16) | 1.18 (0.73–1.90) | 0.78 (0.55–1.10) | 1.33 (0.82–2.17) |
Non-fatal stroke | 1.12 (0.79–1.58) | 0.89 (0.72–1.11) | 0.61 (0.38–0.99) | 0.85 (0.70–1.03) | 0.86 (0.66–1.14) | 0.76 (0.61–0.95) | 0.74 (0.35–1.57) | 0.74 (0.47–1.17) | 1.00 (0.56–1.79) |
CV death | 1.02 (0.89–1.17) | 0.87 (0.78–0.97) | 0.74 (0.58–0.95) | 0.91 (0.83–1.00) | 0.78 (0.68–0.90) | 0.88 (0.79–0.99) | 0.79 (0.57–1.11) | 0.72 (0.50–1.03) | 1.22 (0.70–2.12) |
HHF | 0.96 (0.75–1.23) | 0.87 (0.73–1.05) | 1.11 (0.77–1.61) | 0.94 (0.78–1.13) | 0.93 (0.82–1.04) | 0.93 (0.77–1.12) | 0.86 (0.48–1.55) | 0.61 (0.38–0.98) | 0.95 (0.48–1.88) |
Renal composite outcomeb | NA | 0.78 (0.67–0.92) | 0.64 (0.46–0.88) | NA | NA | 0.85 (0.77–0.93) | NA | 0.68 (0.57–0.79) | NA |
HR, hazard ratio; CI, confidence interval; CVOT, cardiovascular outcome trial; GLP-1RA, glucagon-like peptide 1 receptor agonist; QW, quaque week; ITCA, Implantable Therapeutic Continuous Administration; ELIXA, The Evaluation of Lixisenatide in Acute Coronary Syndrome; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; SUSTAIN 6, Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes 6; EXSCEL, Exenatide Study of Cardiovascular Event Lowering; HARMONY, Albiglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Cardiovascular Disease; REWIND, Researching Cardiovascular Events with a Weekly Incretin in Diabetes; PIONEER 6, Peptide Innovation for Early Diabetes Treatment 6; AMPLITUDE-O, A cardiovascular outcomes study to evaluate the potential of efpeglenatide to reduce cardiovascular risk in adults with type 2 diabetes at high cardiovascular risk; FREEDOM-CVO, Cardiovascular Outcomes Study of ITCA 650 (exenatide) in Adults with Type 2 Diabetes at High Cardiovascular Risk; 3-P MACE, 3-point major adverse cardiovascular events; MI, myocardial infarction; CV, cardiovascular; HHF, hospitalization for heart failure; NA, not available.
a 3-P MACE: a composite of death from CV causes, nonfatal MI, or nonfatal stroke,
b The definition varies according to the trial. LEADER: the new onset of macroalbuminuria or a doubling of the serum creatinine level and an estimated glomerular filtration rate (eGFR) of ≤45 mL/min/1.73 m2, the need for continuous renal-replacement therapy, or death from renal disease; SUSTAIN 6: new or worsening nephropathy includes persistent macroalbuminuria, persistent doubling of the serum creatinine level and a creatinine clearance of less than 45 mL/min/1.73 m2 of body-surface area, or the need for continuous renal-replacement therapy; REWIND: new macroalbuminuria, a sustained decline in estimated glomerular filtration rate of 30% or more from baseline, or chronic renal replacement therapy; AMPLITUDE-O: new macroalbuminuria, ≥30% increase in urine albumin‐to‐creatinine ratio ≥40% decrease in eGFR, or end-stage renal disease.
Trial | Agent |
|||||
---|---|---|---|---|---|---|
Empagliflozin |
Canagliflozin |
Dapagliflozin |
Ertugliflozin |
Sotagliflozin |
||
EMPA-REG OUTCOME [4] | CANVAS [5] | CREDENCE [6] | DECLARE-TIMI 58 [7] | VERTIS-CV [8] | SCORED [9] | |
3-P MACE |
0.86 (0.74–0.99) | 0.86 (0.75–0.97) | 0.80 (0.67–0.95) | 0.93 (0.84–1.03) | 0.97 (0.85–1.11) | 0.84 (0.72–0.99) |
Non-fatal MI | 0.87 (0.70–1.09) | 0.90 (0.71–1.15) | NA | 1.01 (0.84–1.21) | 1.00 (0.76–1.32) | 0.68 (0.52–0.89) |
Non-fatal stroke | 1.24 (0.92–1.67) | 0.85 (0.69–1.05) | NA | 0.89 (0.77–1.01) | 1.00 (0.86–1.27) | 0.66 (0.48–0.91) |
CV death | 0.62 (0.49–0.77) | 0.87 (0.72−1.06) | 0.78 (0.61−1.00) | 0.98 (0.82−1.17) | 0.92 (0.77–1.11) | 0.90 (0.73–1.12) |
HHF | 0.65 (0.50–0.85) | 0.67 (0.52–0.87) | 0.61 (0.47–0.80) | 0.73 (0.61–0.88) | 0.70 (0.54–0.90) | 0.67 (0.55–0.82) |
Renal composite outcome |
0.54 (0.40–0.75) | 0.60 (0.47–0.77) | 0.70 (0.59–0.82) | 0.53 (0.43–0.66) | 0.81 (0.64–1.03) | 0.71 (0.46–1.08) |
Agent |
Lixisenatide |
Liraglutide |
Semaglutide |
Exenatide QW |
Albigutide |
Dulaglutide |
Oral Semaglutide |
Efpeglenatide |
ITCA 650 (Exenatide) |
---|---|---|---|---|---|---|---|---|---|
Trial | ELIXA [10] | LEADER [11] | SUSTAIN 6 [12] | EXSCEL [13] | HARMONY [14] | REWIND [15] | PIONEER 6 [16] | AMPLITUDE-O [17] | FREEDOM-CVO [18] |
3-P MACE |
1.02 (0.89–1.17) | 0.87 (0.78–0.97) | 0.74 (0.58–0.95) | 0.91 (0.83–1.00) | 0.78 (0.68–0.90) | 0.88 (0.79–0.99) | 0.79 (0.57–1.11) | 0.73 (0.58–0.92) | 1.24 (0.90–1.70) |
Non-fatal MI | 1.03 (0.87–1.22) | 0.88 (0.75–1.03) | 0.74 (0.51–1.08) | 0.97 (0.85–1.10) | 0.75 (0.61–0.90) | 0.96 (0.79–1.16) | 1.18 (0.73–1.90) | 0.78 (0.55–1.10) | 1.33 (0.82–2.17) |
Non-fatal stroke | 1.12 (0.79–1.58) | 0.89 (0.72–1.11) | 0.61 (0.38–0.99) | 0.85 (0.70–1.03) | 0.86 (0.66–1.14) | 0.76 (0.61–0.95) | 0.74 (0.35–1.57) | 0.74 (0.47–1.17) | 1.00 (0.56–1.79) |
CV death | 1.02 (0.89–1.17) | 0.87 (0.78–0.97) | 0.74 (0.58–0.95) | 0.91 (0.83–1.00) | 0.78 (0.68–0.90) | 0.88 (0.79–0.99) | 0.79 (0.57–1.11) | 0.72 (0.50–1.03) | 1.22 (0.70–2.12) |
HHF | 0.96 (0.75–1.23) | 0.87 (0.73–1.05) | 1.11 (0.77–1.61) | 0.94 (0.78–1.13) | 0.93 (0.82–1.04) | 0.93 (0.77–1.12) | 0.86 (0.48–1.55) | 0.61 (0.38–0.98) | 0.95 (0.48–1.88) |
Renal composite outcome |
NA | 0.78 (0.67–0.92) | 0.64 (0.46–0.88) | NA | NA | 0.85 (0.77–0.93) | NA | 0.68 (0.57–0.79) | NA |
HR, hazard ratio; CI, confidence interval; CVOT, cardiovascular outcome trial; SGLT2i, sodium-glucose cotransporter 2 inhibitor; EMPA-REG OUTCOME, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; CANVAS, Canagliflozin Cardiovascular Assessment Study; CREDENCE, Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation; DECLARETIMI 58, Dapagliflozin Effect on Cardiovascular Events-Thrombolysis In Myocardial Infarction 58; VERTIS-CV, Evaluation of Ertugliflozin EffIcacy and Safety Cardiovascular Outcomes Trial; SCORED, Effect of Sotagliflozin on Cardiovascular and Renal Events in Participants With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk; 3-P MACE, 3-point major adverse cardiovascular events; MI, myocardial infarction; NA, not available; CV, cardiovascular; HHF, hospitalization for heart failure. 3-P MACE: a composite of death from CV causes, nonfatal MI, or nonfatal stroke, The definition varies according to the trial. EMPA-REG OUTCOME, CANVAS, and DECLARE-TIMI 58: ≥40% decrease in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2, end-stage renal disease, or death from renal cause; CREDENCE: doubling of serum creatinine level, end-stage kidney disease, renal death or CV death; VERTIS-CV: doubling of serum creatinine level, end-stage kidney disease, renal death; SCORED: ≥50% decrease in the eGFR from baseline for ≥30 days, long-term dialysis, renal transplantation, or sustained eGFR of <15 mL/min/1.73 m2 for ≥30 days.
HR, hazard ratio; CI, confidence interval; CVOT, cardiovascular outcome trial; GLP-1RA, glucagon-like peptide 1 receptor agonist; QW, quaque week; ITCA, Implantable Therapeutic Continuous Administration; ELIXA, The Evaluation of Lixisenatide in Acute Coronary Syndrome; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; SUSTAIN 6, Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes 6; EXSCEL, Exenatide Study of Cardiovascular Event Lowering; HARMONY, Albiglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Cardiovascular Disease; REWIND, Researching Cardiovascular Events with a Weekly Incretin in Diabetes; PIONEER 6, Peptide Innovation for Early Diabetes Treatment 6; AMPLITUDE-O, A cardiovascular outcomes study to evaluate the potential of efpeglenatide to reduce cardiovascular risk in adults with type 2 diabetes at high cardiovascular risk; FREEDOM-CVO, Cardiovascular Outcomes Study of ITCA 650 (exenatide) in Adults with Type 2 Diabetes at High Cardiovascular Risk; 3-P MACE, 3-point major adverse cardiovascular events; MI, myocardial infarction; CV, cardiovascular; HHF, hospitalization for heart failure; NA, not available. 3-P MACE: a composite of death from CV causes, nonfatal MI, or nonfatal stroke, The definition varies according to the trial. LEADER: the new onset of macroalbuminuria or a doubling of the serum creatinine level and an estimated glomerular filtration rate (eGFR) of ≤45 mL/min/1.73 m2, the need for continuous renal-replacement therapy, or death from renal disease; SUSTAIN 6: new or worsening nephropathy includes persistent macroalbuminuria, persistent doubling of the serum creatinine level and a creatinine clearance of less than 45 mL/min/1.73 m2 of body-surface area, or the need for continuous renal-replacement therapy; REWIND: new macroalbuminuria, a sustained decline in estimated glomerular filtration rate of 30% or more from baseline, or chronic renal replacement therapy; AMPLITUDE-O: new macroalbuminuria, ≥30% increase in urine albumin‐to‐creatinine ratio ≥40% decrease in eGFR, or end-stage renal disease.