Skip to main content

Table 2 Summary of cardiovascular outcome trials

From: Consensus recommendations for management of patients with type 2 diabetes mellitus and cardiovascular diseases

Drug class Trial/drug Inclusion criteria Prior CVD/CHF (%) No. of patients Primary endpoint [HR (95% CI)] Key secondary endpoints [HR (95% CI)]
Relative risk reduction (%) Relative risk reduction (%)
Unstable angina hospitalisation Stroked MId CV death HF hospitalisation All-cause mortality
Biguanide UKPDS/metformin Newly diagnosed T2DM patients aged 25–65 years and had a fasting plasma glucose > 6 mmol/L on two mornings, 1–3 weeks apart NR 1704 0.68 (0.53–0.87) NR 0.59 (0.29–1.18) 0.61 (0.41–0.69) 0.58 (0.37–0.91) 0.79 (0.27–1.07) 0.64 (0.45–0.91)
39 24
DPP4 inhibitors SAVOR TIMI 5325/saxagliptin T2DM and history of or multiple risk factors for CVD 78/13 16,492 3-point MACE
1.00 (0.89–1.12) 		1.27 (1.07–1.51) 1.11 (0.88–1.39) 0.95 (0.80–1.12) 1.03 (0.87–1.22) 1.27 (1.07–1.51) 1.11 (0.96–1.27)
CARMELINA/linagliptin T2DM and high CV risk [history of vascular disease and urine-albumin creatinine ratio > 200 mg/g)], and high renal risk (reduced eGFR and micro- or macroalbuminuria) 58/46 6991 3-point MACE
1.02 (0.89–1.17) 		0.87 (0.57–1.31) 0.88 (0.63–1.23) 1.15 (0.91–1.45) 0.96 (0.81–1.14) 0.90 (0.74–1.08) 0.98 (0.84–1.13)
EXAMINE/alogliptin T2DM and ACS within 15–90 days before randomization 100/28 5380 3-point MACE
0.96 (≤ 1.16)* 		0.90 (0.60–1.37) 0.91 (0.55–1.50) 1.08 (0.88–1.33) 0.85 (0.66–1.10) 1.19 (0.90–1.58) 0.88 (0.71–1.09)
TECOS/sitagliptin T2DM and pre-existing CVD 74/18 14,671 4-point MACE
0.98 (0.88–1.09) 		0.90 (0.70–1.16) 0.97 (0.79–1.19) 0.95 (0.81–1.11) 1.03 (0.89–1.19) 1.00 (0.83–1.20) 1.01 (0.90–1.14)
SGLT2 inhibitor EMPA-REG OUTCOME/empagliflozin T2DM and pre-existing CVD, with BMI ≤ 45 kg/m2 and eGFR ≥ 30 mL/min/1.73 m2 99/10 7020 3-point MACE
0.86 (0.74–0.99) 		0.99 (0.74–1.34) 1.18 (0.89–1.56) 0.87 (0.70–1.09) 0.62 (0.49–0.77) 0.65 (0.50–0.85) 0.68 (0.57–0.82)
14 24 13 38 35 32
Integrated CANVAS programme (CANVAS, CANVAS-R)/canagliflozin T2DM and pre-existing CVD at ≥ 30 years of age or ≥ 2 CV risk factors (T2DM ≥ 10 years, systolic blood pressure > 140 mmHg and on anti-hypertensive agents, current smoking, micro- or macroalbuminuria) at ≥ 50 years of age 65.6/14.4 10,142 3-point MACE
0.86 (0.75–0.97)b 		NR 0.87 (0.69–1.09)b 0.89 (0.73–1.09)b 0.96 (0.77–1.18)c, 0.87 (0.72–1.06)b 0.67 (0.52–0.87)b 0.87 (0.74–1.01), 0.90 (0.76–1.07)b
14 10 15 13 33 10
DECLARE-TIMI 58/dapagliflozin T2DM with creatinine clearance of ≥ 60 mL/min, eGFR < 60 mL/min/1.73 m2, had multiple risk factors for ASCVD or had established ASCVD (clinically evident ischemic heart disease, ischemic cerebrovascular disease, or peripheral artery disease) 41/10 17,160 Total cohort, 0.93 (0.84–1.03); ASCVD, 0.90 (0.79–1.02); multiple risk factors without ASCVD, 1.01 (0.86–1.20) NR 1.01 (0.84–1.21) 0.89 (0.77–1.01) Total cohort, 0.98 (0.82–1.17); ASCVD, 0.83 (0.71–0.98); multiple risk factors without ASCVD, 0.84 (0.67–1.04) Total cohort, 0.73 (0.61–0.88); ASCVD, 0.83 (0.71–0.98); multiple risk factors without ASCVD, 0.84 (0.67–1.04) 0.93 (0.82–1.04)
GLP1-receptor agonist LEADER/liraglutide T2DM and pre-existing CVD, kidney disease, or HF at ≥ 50 years of age or ≥ 1 CV risk factor at ≥ 60 years of age (microalbuminuria or proteinuria, hypertension and left ventricular hypertrophy, left ventricular systolic or diastolic dysfunction) 81/18 9340 3-point MACE 0.87 (0.78–0.97) 0.98 (0.76–1.26) 0.86 (0.71–1.06) 0.86 (0.73–1.00) 0.78 (0.66–0.93) 0.87 (0.73–1.05) 0.85 (0.74–0.97)
13 11 12 22 13 15
SUSTAIN-6/semaglutide T2DM and pre-existing CVD, HF, or CKD at ≥ 50 years 60/24 3297 3-point MACE
0.74 (0.58–0.95) 		0.82 (0.47–1.44) 0.61 (0.38–0.99) 0.74 (0.51–1.08) 0.98 (0.65–1.48) 1.11 (0.77–1.61) 1.05 (0.74–1.50)
6 39 26 2 11 5
ELIXA/lixisenatide T2DM and an acute coronary event within 180 days before screening 100/22 6068 4-point MACE
1.02 (0.89–1.17) 		1.11 (0.47–2.62) 1.12 (0.79–1.58) 1.03 (0.87–1.22) 0.98 (0.78–1.22) 0.96 (0.75–1.23) 0.94 (0.78–1.13)
EXSCEL/exenatide T2DM with or without pre-existing CVD 73.1/16.2 14,752 3-point MACE
0.91 (0.83–1.00) 		1.05 (0.94–1.18) 0.85 (0.70–1.03) 0.97 (0.85–1.10) 0.88 (0.76–1.02) 0.94 (0.78–1.13) 0.86 (0.77–0.97)
Harmony/albiglutide T2DM and established disease of MI, ≥ 50% carotid artery stenosis/peripheral artery circulation at ≥ 40 years 87/– 9463 3-point MACE
0.78 (0.68–0.90) 		NR NR 0.75 (0.61–0.90) 0.93 (0.73–1.19) 0.85 (0.70–1.04) (composite of CV death and HF hospitalization) 0.95 (0.79–1.16)
Thiazolidinediones IRIS/pioglitazone Insulin resistance but not diabetes + ischemic stroke or TIA in 6 months before randomization 100/– 3876 Composite of fatal and nonfatal stroke and MI
0.76 (0.62–0.93) 		NR 0.82 (0.61–1.10) NR NR – 0.93 (0.73–1.17)
18 20
PROactive/pioglitazone T2DM with history of pre-existing macrovascular disease (MI, stroke, percutaneous coronary intervention or coronary artery bypass surgery ≥ 6 months of study, ACS ≥ 3 months before study entry, or objective evidence of coronary artery disease or obstructive arterial disease in the leg) making the patient population at very high-risk for macrovascular disease 100/– 5238 Composite MACE
0.90 (0.80–1.02)a 		NR 0.80 (0.72–0.98) (composite of all-cause mortality, MI, stroke) 0.80 (0.72–0.98) 0.90 (0.80–1.02) NR 0.80 (0.72–0.98)
10 16 16 16
Insulin ORIGIN/insulin glargine T2DM with CV risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine 59/– 12,537 1.02 (0.94–1.11) 0.91 (0.76–1.08) 1.03 (0.89–1.21) 1.02 (0.88–1.19) 1.00 (0.89–1.13) 0.90 (0.77–1.05) 0.98 (0.90–1.08)
DEVOTE/degludec T2DM, age > 50 years + history of CVD and/or CKD, age > 60 years + > 1 CV risk factors 83/– 7637 3-point MACE 0.91 (0.78–1.06) 0.95 (0.68–1.31) 0.90 (0.65–1.23) 0.85 (0.68–1.06) 0.96 (0.76–1.21) NR 0.91 (0.76–1.11)
α-glucosidase inhibitors ACE/acarbose Coronary heart disease and impaired glucose tolerance (conducted in China) 100/3.7 6522 5-point MACE
0.98 (0.86–1.11) 		1.02 (0.82–1.26) 0.97 (0.70–1.33) 1.12 (0.87–1.46) 0.89 (0.71–1.11) 0.89 (0.63–1.24) 0.98 (0.81–1.19)
  1. ACS acute coronary syndrome, ASCVD atherosclerotic cardiovascular disease, MACE major adverse cardiovascular event, CKD chronic kidney disease, CVD cardiovascular disease, MI myocardial infarction, HF heart failure, HR hazard ratio, TIA transient ischaemic attack, T2DM type 2 diabetes mellitus, DPP4 dipeptidylpeptidase-4, GLP1 glucagon like peptide 1, NR not reported, SGLT2i sodium–glucose cotransporter 2 inhibitor. Full names of all the cardiovascular outcome trials have been mentioned in the ‘abbreviations’ section of the manuscript. Primary endpoints: 3-point MACE: CV death, non-fatal MI, non-fatal stroke, 4-point MACE: 3-point MACE + hospitalisation for unstable angina, 5-point MACE: 3-point MACE + hospitalization for HF or unstable angina, – not available
  2. aComposite MACE (PROactive trial): CV death, non-fatal MI (including silent MI), stroke acute coronary syndrome, coronary or leg artery revascularization, or above the ankle amputation
  3. bNon-truncated integrated data (refers to pooled data from CANVAS, including before 20 November 2012 plus CANVAS-R)
  4. cTruncated integrated data set (refers to pooled data from CANVAS after 20 November 2012 plus CANVAS-R; pre-specified in treating hierarchy as the principal data set for analysis for superiority of all-cause mortality and CV death in the CANVAS Program)
  5. dReported for fatal and nonfatal events in all trials except EXAMINE, ELIXA, and SUSTAIN-6, which reported for nonfatal events only
Back to article page

Diabetology & Metabolic Syndrome

ISSN: 1758-5996

Contact us