Practical guide: Glucagon-like peptide-1 and dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists in diabetes mellitus

Table 2 Cardiovascular outcome trials of glucagon-like peptide-1 and dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists

Trial name	No. of patients	Study population	Active comparator	Follow-up	Outcomes
LEADER	9340	T2DM, ≥ 50 yr with established CVD, or age ≥ 60 yr with CV risk factors	1.8 mg of liraglutide once-daily SC	3.8 yr	13% reduction in MACEs; 15% reduction in overall mortality; 22% reduction in CV-related deaths
SUSTAIN-6	3297	T2DM, ≥ 50 yr with established CVD, or CKD ≥ stage 3, or age ≥ 60 yr with CV risk factors	0.5 mg or 1.0 mg semaglutide once-weekly SC	2.1 yr	26% reduction in MACEs; 39% reduction in non-fatal stroke
PIONEER 6	3183	T2DM, ≥ 50 yr with established CVD, or CKD ≥ stage 3, or age ≥ 60 yr with CV risk factors	14 mg of semaglutide once-daily oral	1.3 yr	No significant reduction in MACEs; 51% significant reduction in CV-related deaths
AMPLITUDE-O	4076	T2DM, ≥ 50 yr with established CVD, or CKD ≥ stage 3 with CV risk factors	4 or 6 mg of efpeglenatide once-weekly SC	1.81 yr	27% reduction in MACEs; reduced risk of hospitalization for heart failure
HARMONY	9463	T2DM, age ≥ 40 yr with CVD	30-50 mg of albiglutide once-weekly SC	1.6 yr	22% reduction in MACEs
SURPASS-4	2002	T2DM, ≥ 18 yr with established CVD, or with CV risk factors	5 mg, 10 mg, or 15 mg of tirzepatide once-weekly SC	2 yr	Tirzepatide treatment was not associated with increased CV risk

MACEs: Major adverse cardiac events, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for unstable angina; CKD: Chronic kidney disease; CV: Cardiovascular; CVD: Cardiovascular disease; T2DM: Type 2 diabetes mellitus; SC: Subcutaneous; LEADER: Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; SUSTAIN-6: Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes 6.