Table 2.

Trial Data Investigating Change in CVD Risk With the Use of Glucagon‐Like Peptide‐1 Receptor Agonists in Patients With T2D

Study	Study design and population	Treatment arms	Median follow‐up period	Primary composite end point, time to first occurrence	Primary outcome, active trial drug vs placebo, % of patients
ELIXA 52	Double‐blind, randomized placebo‐controlled trial in people with T2D who had a recent acute coronary syndrome	Once‐daily subcutaneous lixisenatide 20 μg (n=3034) vs placebo (n=3034)	25 mo	Cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina	13.4% vs 13.2% (HR, 1.02 [95% CI, 0.89–1.17]; P<0.001 for noninferiority; P=0.81 for superiority)
LEADER 53	Double‐blind, randomized placebo‐controlled trial in people with T2D and high cardiovascular risk	Once‐daily subcutaneous liraglutide 1.8 mg (n=4668) vs placebo (n=4672)	3.8 y	Death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke	13.0% vs 14.9% (HR, 0.87 [95% CI, 0.78–0.97]; P<0.001 for noninferiority; P=0.01 for superiority)
SUSTAIN 6 54	Double‐blind, randomized placebo‐controlled trial in people with T2D at high cardiovascular risk	Once‐weekly subcutaneous semaglutide 0.5–1.0 mg (n=1648) vs placebo (n=1649)	2.1 y	Cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke	6.6% vs 8.9% (HR, 0.74 [95% CI, 0.58–0.95]; P<0.001 for noninferiority, P=0.02 for superiority)
PIONEER‐6 55	Double‐blind, randomized placebo‐controlled trial in people with T2D with high cardiovascular risk	Once‐daily oral semaglutide 14 mg (n=1591) vs placebo (n=1592)	15.9 mo	Major adverse cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke)	3.8% vs 4.8% (HR, 0.79 [95% CI, 0.57–1.11]; P<0.001 for noninferiority, P=0.17 for superiority)
EXSCEL 56	Double‐blind, randomized placebo‐controlled trial in people with T2D with or without previous CVD	Once‐weekly subcutaneous exenatide 2 mg (n=7356) vs placebo (n=7396)	3.2 y	Death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke	11.4% vs 12.2% (HR, 0.91 [95% CI, 0.83–1.00]; P<0.001 for noninferiority; P=0.06 for superiority)
Harmony Outcomes 58	Double‐blind, randomized placebo‐controlled trial in people with T2D and CVD	Once‐weekly subcutaneous albiglutide 30–50 mg (n=4731) vs placebo (n=4732)	1.6 y	Cardiovascular death, myocardial infarction, or stroke	7% vs 9% (HR, 0.78 [95% CI, 0.68–0.90]; P<0.0001 for noninferiority; P=0.0006 for superiority)
REWIND 59	Double‐blind, randomized placebo‐controlled trial in people with T2D with previous CVD or cardiovascular risk factors	Once‐weekly subcutaneous dulaglutide 1.5 mg (n=4949) vs placebo (n=4952)	5.4 y	Nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (including unknown causes)	12.0% vs 13.4% (HR, 0.88 [95% CI, 0.79–0.99]; P=0.026)
AMPLITUDE‐O 60	Blinded, randomized placebo‐controlled trial in people with T2D and a history of CVD or current kidney disease with at least 1 additional cardiovascular risk factor	Once‐weekly subcutaneous efpeglenatide 4 or 6 mg (n=2717) vs placebo (n=1359)	1.8 y	Major adverse cardiovascular event (nonfatal myocardial) infarction, nonfatal stroke, or death from cardiovascular or undetermined causes	7.0% vs 9.2% (HR, 0.73 [95% CI, 0.58–0.92]; P<0.001 for noninferiority; P=0.007 for superiority)

AMPLITUDE‐O indicates Effect of Efpeglenatide on Cardiovascular Outcomes; CVD, cardiovascular disease; ELIXA, Evaluation of Lixisenatide in Acute Coronary Syndrome; EXSCEL, Exenatide Study of Cardiovascular Event Lowering Trial; HR, hazard ratio; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; mo, months PIONEER‐6, Peptide Innovation for Early Diabetes Treatment 6; REWIND, Researching Cardiovascular Events With a Weekly Incretin in Diabetes; SUSTAIN 6, Trial to Evaluate Cardiovascular and Other Long‐term Outcomes With Semaglutide in Subjects With Type 2 Diabetes; T2D, type 2 diabetes; and y, years.