Alternative GLP-1 Receptor Agonist Options for Type 2 Diabetes

Primary Recommendation: Liraglutide

The American College of Cardiology recommends liraglutide as the preferred alternative GLP-1 receptor agonist for patients unable to take Jardiance, due to its demonstrated cardiovascular benefit in major outcome trials and its use across a wide range of kidney function 1, 2, 3
Liraglutide provides proven cardiovascular benefit with reduction in major adverse cardiovascular events (MACE) including cardiovascular deaths, nonfatal MI, and nonfatal strokes independent of glucose control 1, 3
Liraglutide offers kidney protection with reduced albuminuria and slowed eGFR decline, with particularly strong MACE risk reduction in patients with eGFR <60 mL/min/1.73 m² 2
No dose adjustment is required for patients with chronic kidney disease, including those with eGFR as low as 15 mL/min/1.73 m² 2
Liraglutide has a low hypoglycemia risk when used without sulfonylureas or insulin 2

Exenatide once-weekly at 2 mg subcutaneously weekly is an alternative option that has demonstrated cardiovascular safety, but it should not be used if eGFR <30 mL/min/1.73 m² 1, 2
Exenatide requires dose adjustment in moderate renal impairment 2

The American College of Cardiology advises avoiding all GLP-1 receptor agonists in patients with personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia type 2 (MEN2) 4
Active gallbladder disease, history of gastroparesis, and recent heart failure decompensation are also contraindications for GLP-1 receptor agonists 4, 5

The American College of Cardiology recommends monitoring glucose closely for the first 4 weeks after initiating liraglutide, especially if on insulin, sulfonylureas, or glinides 4
Consider reducing sulfonylurea dose or discontinuing it entirely to minimize hypoglycemia risk, and reduce total daily insulin dose by approximately 20% at initiation 4