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. 2023 Apr 10;8:152. doi: 10.1038/s41392-023-01400-z

Table 1.

Cardiovascular outcomes trials (including stroke) in diabetes mellitus (2013–2022)

Clinical trial Clinical trials’ number Year Phase Participants (n) Intervention Follow-up Main outcome
Dipeptidyl peptidase-4 (DPP-4) inhibitors
CARMELINA475 NCT01897532 2013–2016 3 6991

I: Iinagliptin

C: placebo

 2.2 years Cardiovascular death, nonfatal myocardial infarction, nonfatal stroke
NA476 NCT01703208 2012–2016 3 4202

I: Omarigliptin

C: placebo

 1.84 years Major adverse cardiovascular event, hospitalization for heart failure
SAVOR-TIMI 5345 NCT01107886 2010-2011 3 16492

I: Saxagliptin

C: placebo

 2.1 years Composite of cardiovascular death, myocardial infarction, or ischemic stroke
TECOS477 NCT00790205 2008–2012 3 14671

I: Sitagliptin

C: placebo

 3 years Composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina
Glucagon-like peptide-1 receptor (GLP-1) agonists
REWIND478 NCT01394952 2011 3 9901

I: Dulaglutide

C: placebo

 5.4 years Nonfatal myocardial infarction, nonfatal stroke, and death from cardiovascular
SUSTAIN-644 NCT01720446 2013 3 3297

I: Semaglutide

C: placebo

 2.1 years Cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke
PIONEER 6479 NCT02692716 2017 3 3183

I: oral Semaglutide

C: placebo

 1.25years Death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke
EXSCEL480 NCT01144338 2010-2015 3 14752

I: Exenatide

C: placebo

 3.2 years Death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke
LEADER481 NCT01179048 2010–2012 3 9340

I: Liraglutide

C: placebo

 3.8 years Death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke
ELIXA482 NCT01147250 2010–2013 3 6991

I: Lixisenatide

C: placebo

 2.2 years Death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina
Sodium-glucose cotransporter-2 (SGLT2) inhibitors
EMPA-REG OUTCOME483 NCT01131676 2015 3 7020

I: Empagliflozin

C: placebo

 3.1 years MACE, cardiovascular, all-cause death, hospitalization for heart failure
CANVAS program484,485 NCT01032629 NCT01989754 2017 3 10142

I: Canagliflozin

C: placebo

 3.61 years Cardiovascular death or hospitalized Heart failure
DAPA-HF486 NCT03619213 2018–2022 3 3131

I: Dapagliflozin

C: placebo

 2.3 years Composite of worsening heart failure, cardiovascular death
Empa-HF100 NCT03485092 2018 3 150

I: Empagliflozin

C: placebo

 0.69 year Left ventricular volumes
CREDENCE487 NCT02065791 2014–2017 3 4401

I: Canagliflozin

C: placebo

 2.62 years Reduces the risk of kidney failure and cardiovascular events
DECLARE–TIMI 58488 NCT01730534 2013–2018 3 17160

I:Dapagliflozin

C: placebo

 4.2 years MACE, composite of cardiovascular death, hospitalization for heart failure
EMPA-REG489 NCT01131676 2010–2013 3 7020

I:Empagliflozin

C: placebo

 3.1 years Death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke
Others
SAVOR-TIMI 53490 NCT01107886 2010-2011 / 4894

I: Metformin

C:Other antidiabetic drugs

 2.1 years Composite of cardiovascular death, myocardial infarction, or ischemic stroke
TOSCA.IT491 NCT00700856 2008–2014 3 3028

I: pioglitazone add on metformin

C: sulfonylurea add on metformin

 5 years All-cause death, nonfatal myocardial infarction, nonfatal stroke, or urgent coronary revascularization
PROactive492 NCT00013208 2015 / 3606

I: Pioglitazone

C: placebo

 7.8 years All-cause mortality, nonfatal myocardial infarction, stroke, cardiovascular mortality, cardiac intervention, et al
PROFIT-J493 UMIN000000846 2007–2011 3 481

I: Pioglitazone

C: Other antidiabetic drugs

 1.53/1.64 years Composite of all-cause death, nonfatal cerebral infarction, and nonfatal myocardial infarction
DEVOTE494 NCT01959529 2013–2014 3 7637

I: Insulin Degludec

C: Insulin Glargine

 1.99 years Death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke
ORIGINALE495,496 NCT00069784 2012–2014 3 4718

C: Glargine

I: Standard care

 2.7 years Death from cardiovascular causes or myocardial infarction or stroke and any of these three outcomes or hospitalization for heart failure or carotid, coronary, or peripheral revascularization
ACCORD497 NCT00000620 2001–2005 3 10251

I: intensive glycemic control

C: standard glycemic control

 3.7 years Composite cardiovascular outcome, cardiovascular and total mortality, nonfatal myocardial infarction
Steno-2498,499 NCT00320008 1993–2006 3 160

I: intensive glycemic control

C: standard glycemic control

 13.3 years

Death from any cause

Stroke
VADT500 NCT00032487 2000–2008 3 1791

I: intensive glycemic control

C: standard glycemic control

 5.6 years Composite of major cardiovascular events
Look AHEAD77 NCT00017953 2001–2012 3 5145

I: intensive lifestyle intervention

C: receive diabetes support and education

 9.6 years Composite cardiovascular outcome
AleCardio501 NCT01042769 2010–2012 3 7226

I: Aleglitazar

C: placebo

 2.5 years Composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke

MACE major adverse cardiovascular events, NA no official trial name