GLP-1 Receptor Agonists and Cardiovascular Disease in Patients with Type 2 Diabetes

Table 2

Comparison of studies conducted to evaluate cardiovascular events in drugs for type 2 diabetes.

(a)

	Drug	Intervention	Primary endpoint\	N	Follow-up time; (years)	Mean age	Mean HbA1c levels (%)	Previous cardiovascular status of patients
SAVOR TIMI	Saxagliptin	Add saxagliptin versus placebo to standard of care	CV death, AMI, or stroke	18,206	2.1	≥40	≥6.5	CVD or high cardiovascular risk
EXAMINE	Alogliptin	Add alogliptin versus placebo to standard of care	CV death, AMI, or stroke	5380	1.5	≥18	6.5–11	Acute coronary syndrome within previous 15–90 days
TECOS	Sitagliptin	Sitagliptin versus placebo	CV death, AMI, unstable angina, or stroke	14,724	3	≥50	6.5–11	Preexisting CVD
ELIXA	Lixisenatide	Lixisenatide versus placebo	CV death, AMI, unstable angina, or stroke	6076	2.1	≥30	≥7	Acute coronary syndrome within previous 180 days
EMPA-REG; outcome	Empagliflozin	Empagliflozin 10 mg versus 25 mg versus placebo	CV death, AMI, or stroke	7000	3.1	≥18	7–10	Preexisting CVD
LEADER	Liraglutide	Liraglutide versus placebo	CV death, AMI, or stroke	9340	3.8	≥50	≥7	≥50 yrs with preexisting disease: CVD/cerebrovascular/renal disease/HF or ≥60 yrs with high CV risk
SUSTAIN-6	Semaglutide	Semaglutide 0.5 mg versus 1 mg versus placebo	CV death, AMI, or stroke	3299	1.99	≥50	≥7	≥50 yrs with preexisting CVD or ≥60 yrs with high cardiovascular risk
EXSCEL	Exenatide	Exenatide 2 mg weekly versus placebo	CV death, AMI, or stroke	14,752	3.2	≥50	6.5–10	70% preexisting CVD
CANVAS	Canagliflozin	CANVAS; Canagliflozin 300 mg versus canagliflozin 100 mg versus placebo	CV death, AMI, or stroke	10,142; (4330 CANVAS, 5812 CANVAS-R)	5.69 (CANVAS); 2 (CANVAS-R)	≥50	7–10.5	≥30 yrs with atherosclerotic disease or ≥50 yrs with 3 or more CV risk factors
		CANVAS-R; Canagliflozin 100 mg with optional increase to 300 mg versus placebo

(b)

Cardiovascular event endpoints

SAVOR TIMI

EXAMINE

TECOS

ELIXA

EMPA-REG

LEADER

SUSTAIN-6

EXSCEL

CANVAS

Class

HR

Class

HR

Class

HR

Class

HR

Class

HR

Class

HR

Class

HR

Class

HR

Class

Primary composite endpoint; MACE

CV death, AMI, or stroke

1 ()

CV death, AMI, or stroke

0.96 ()

CV death, AMI, unstable angina, or stroke

0.98 ()

CV death, AMI, unstable angina, or stroke

1.02 ()

CV death, AMI, or stroke

0.86 ()

CV death, AMI, or stroke

0.87 ()

CV death, AMI, or stroke

0.74; ()

CV death, AMI, or stroke

0.91; ()

CV death, AMI, or stroke

CV death

Primary endpoint

1.03 ()

Primary endpoint

0.85 ()

Primary endpoint

1.03 ()

Primary endpoint

0.98 ()

Primary endpoint

0.62 ()

Primary endpoint

0.78 ()

Primary endpoint

0.98 ()

Secondary endpoint

0.88; (ns)

Secondary endpoint

AMI

Primary endpoint

0.95 ()

Primary endpoint

1.08 ()

Primary endpoint

0.95 ()

Primary endpoint

1.03 ()

Primary endpoint

0.87 ()

Primary endpoint

0.86 ()

Primary endpoint

0.74 ()

Secondary endpoint

2.1; (ns)

Secondary endpoint

Stroke

Primary endpoint

1.11 ()

Primary endpoint

0.91 ()

Primary endpoint

0.97 ()

Primary endpoint

1.12 ()

Primary endpoint

1.18 ()

Primary endpoint

0.86 ()

Primary endpoint

0.61 ()

Secondary endpoint

0.9; (ns)

Secondary endpoint

Hospitalisation unstable angina

Secondary endpoint

1.19 ()

Secondary endpoint

0.90 ()

Primary endpoint

0.90 ()

Primary endpoint

1.11 ()

Secondary endpoint

0.99 ()

Expanded primary endpoint

0.98 ()

Expanded primary endpoint

0.82 ()

Secondary endpoint

2.5; (ns)

Hospitalization heart failure

Secondary endpoint

1.27 (7)

Expanded primary endpoint

1.19 ()

Secondary endpoint

1 ()

Secondary endpoint

0.96 ()

Secondary endpoint

0.65 ()

Expanded primary endpoint

0.87 ()

Expanded primary endpoint

1.11 (p = 0.57)

Secondary endpoint

1; (ns)

Secondary endpoint

AMI: acute myocardial infarction; CV: cardiovascular; CVD: cardiovascular disease; HF: heart failure; HR: hazard ratio; MACE: major adverse cardiovascular events.