Introduction
Class*† | SGLT2 inhibitors | GLP-1 receptor agonists | ||||
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Study | EMPA-REG OUTCOME Empagliflozin | CANVAS Programme Canagliflozin | AMPLITUDE-O Liraglutide | LEADER Liraglutide | SUSTAIN-6 Semaglutide | REWIND Dulaglutide |
MACE‡ HR (95% CI) ER drug vs placebo/1,000 PY | 0.86 (0.74–0.99) 37 vs 44 | 0.86 (0.75–0.97) 27 vs 32 | 0.73 (0.58–0.92) 39 vs 53 | 0.87 (0.78–0.97) 34 vs 39 | 0.74 (0.58–0.95) 32 vs 44 | 0.88 (0.79–0.99) 24 vs 27 |
CV death HR (95% CI) | 0.62 (0.49–0.77) All-cause death also reduced | 0.87 (0.72–1.06)–N.S | 0.72 (0.50–1.03)–N.S | 0.78 (0.66–0.93) All-cause death also reduced | 0.98 (0.65–1.48)–N.S | 0.91 (0.78–1.06)–N.S |
Nonfatal MI HR (95% CI) | 0.87 (0.70–1.09)–N.S | 0.85 (0.69–1.05)–N.S | 0.78 (0.55–1.10)–N.S | 0.88 (0.75–1.03)–N.S | 0.74 (0.51–1.08)–N.S | 0.96 (0.79–1.16)–N.S |
Nonfatal stroke HR (95% CI) | 1.24 (0.92–1.67)–N.S | 0.90 (0.71–1.15) – N.S | 0.80 (0.48–1.31) – N.S | 0.89 (0.72–1.11) – N.S | 0.61 (0.38–0.99) | 0.76 (0.61–0.95) |
Other cardiorenal benefits (individual secondary endpoints) | Protective effect on: • HHF • Impaired renal function • Albuminuria | Protective effect on: • HHF • Impaired renal function • Albuminuria | Protective effect on: • HF • A composite of impaired renal function or albuminuria • Albuminuria | Protective effect on albuminuria | Protective effect on albuminuria | Protective effect on: • Impaired renal function • Albuminuria |
Cohort composition | ||||||
Number of participants | 7020 | 10,142 | 4076 | 9340 | 3297 | 9901 |
Established CVD % pts | 99% | 65% | 91% | 82% | 83% | 31% |
Mean eGFR mL/min/1.73 m2 | 74 | 77 | 73 | 80 | 76 | 75 |
Key inclusion criteria (in addition to T2D) | Age ≥ 18 years with established CVD | • Age ≥ 30 years with symptomatic ASCVD • or ≥ 50 years with ≥ 2 CV risk factors | • Age ≥ 18 years with history of CVD • or ≥ 50 years (male) or ≥ 55 years (female) with kidney disease and ≥ 1 CV risk factor | • Age ≥ 50 years with ≥ 1 CV condition • or ≥ 60 years with ≥ 1 CV risk factor | • Age ≥ 50 years with established CVD, chronic HF or chronic kidney disease (> stage 3) • or ≥ 60 years with ≥ 1 CV risk factor | • Age ≥ 50 years with vascular disease • or ≥ 55 years with ≥ 1 cardiorenal condition • or ≥ 60 years with ≥ 2 CV risk factors |
Subgroup analyses | ||||||
Secondary vs primary CVD prevention MACE‡ HR (95% CI) | N/A | Secondary prevention group: 0.82 (0.72–0.95) Primary prevention group: 0.98 (0.74–1.30) P = 0.18 | Secondary prevention group: 0.71 (0.57–0.90) Primary prevention group: 1.71 (0.48–6.07) | Secondary prevention group: 0.83 (0.74–0.93) Primary prevention group: 1.20 (0.86–1.67) P = 0.04 | Secondary prevention group: 0.72 (0.55–0.93) Primary prevention group: 1.00 (0.41–2.46) P = 0.49 | Secondary prevention group: 0.87 (0.74–1.02) Primary prevention group: 0.87 (0.74–1.02) P = 0.97 |
Other subgroups | Relative risk reduction for 3P-MACE was in most cases broadly similar across demographic and clinical baseline characteristics, including a range of cardiovascular and renal characteristics |
Guidelines | Selected recommendations for CVD management based on diabetes CVOTs |
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ADA 2022 | For patients with T2D who have established ASCVD or high / very high CV risk, SGLT2 inhibitors or GLP-1 RA with proven cardiovascular benefit are recommended as part of glycaemic management:* • Either a GLP-1 RA with proven CVD benefit or an SGLT2 inhibitor with proven CVD benefit • If further intensification is required or the patient is now unable to tolerate a GLP-1 RA and/or SGLT2 inhibitor choose agents demonstrating CV safety; consider adding the other class (GLP-1 RA or SGLT2 inhibitor) with proven CVD benefit† |
ACC 2020 | For patients with T2D who have established or high risk of ASCVD consider an SGLT2 inhibitor or GLP-1 RA with proven CV benefit |
ADA and EASD 2019 | For patients with T2D who have established ASCVD, an SGLT2 inhibitor or GLP-1 RA with proven cardiovascular benefit is recommended as part of glycaemic management: • First-line therapy is metformin • Add an GLP-1 RA with proven CVD benefit or, if eGFR is adequate, an SGLT2 inhibitor with proven CVD benefit • If further intensification is required or the patient is now unable to tolerate a GLP-1 RA and/or SGLT2 inhibitor, choose agents demonstrating CV safety† |
ESC (in association with EASD) 2019 | Consider CV risk independently of Hb1Ac; for patients with T2D who have ASCVD, or high/very high CV risk (target organ damage or multiple risk factors) • SGLT2 inhibitor or GLP-1 RA (either as first add-on to metformin or as monotherapy; however, drug labels stipulate that metformin should be first line) • If HbA1c is above target, consider adding the other class (GLP-1 RA or SGLT2i) with proven CVD benefit |