The role of GLP-1 receptor agonists in managing type 2 diabetes

Article Figures & Data

TABLE 1

Glucagon-like peptide-1 receptor agonists approved for use in the United States

Drug	Available doses	Frequency and route	Dose approved for weight management
Exenatide	5 μg, 10 μg	Twice daily subcutaneously	Not approved
Liraglutide	0.6 mg, 1.2 mg, 1.8 mg	Once daily subcutaneously	0.6 mg once daily for 1 week, increase by 0.6 mg daily at weekly intervals to a target dose of 3 mg once daily
Exenatide extended-release	2 mg	Once weekly subcutaneously	Not approved
Dulaglutide	0.75 mg, 1.5 mg, 3 mg, 4.5 mg	Once weekly subcutaneously	Not approved
Semaglutide	0.25 mg, 0.5 mg, 1 mg, 2 mg	Once weekly	Titrate every 4 weeks: 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg once weekly
Semaglutide, oral	3 mg, 7 mg, 14 mg	Once daily by mouth	Not approved
Liraglutideinsulin degludec	0.36 mg-10 U 0.5 mg-16 U	Once daily subcutaneously	Not approved
Lixisenatideinsulin glargine	5 μg-15 U 10 μg-30 U	Once daily subcutaneously	Not approved
Tirzepatide	2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg	Once weekly subcutaneously	Not approved

TABLE 2

Effects of glucagon-like peptide-1 receptor agonistson major adverse cardiovascular events in clinical trials

Trial	Number of patients	Median follow-up	Cardiovascular disease at baseline^a	Treatment	Number needed to treat^b
REWIND¹⁵	9,901	5.4 years	31.5%	Dulaglutide 1.5 mg subcutaneously weekly	323
SUSTAIN-6¹⁶	3,297	2.1 years	2.1 years 60.5%	Semaglutide 0.5 or 1 mg subcutaneously weekly	83
LEADER¹⁷	9,340	3.8 years	81.3%	Liraglutide 1.6 mg subcutaneously daily	200
ELIXA¹⁸	6,068	2.1 years	100%	Lixisenatide 10 or 20 μg subcutaneously daily	No benefit
EXSCEL¹⁹	14,752	3.2 years	70%	Exenatide extended-release 2 mg subcutaneously weekly	No benefit
PIONEER-6²¹	3,183	1.3 years	85%	Semaglutide 14 mg by mouth daily	No benefit

↵a All patients had longstanding type 2 diabetes and also either had a history of cardiovascular disease or were at risk of it.
↵b Number of patients needed to be treated for 1 year to prevent 1 major adverse cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes, plus, in the ELIXA trial, hospitalization for heart failure), calculated as the inverse of the absolute risk reduction.
ELIXA = Lixisenatide in Patients With Type 2 Diabetes and Acute Coronary Syndrome; EXSCEL = Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes; LEADER = Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; PIONEER-6 = Oral Semaglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes; REWIND = Researching Cardiovascular Events With a Weekly Incretin in Diabetes; SUSTAIN-6 = Semaglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes