GLP-1 Receptor Agonists in Medical Practice

Patient Selection

GLP-1 receptor agonists are absolutely contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2), as recommended by the American College of Cardiology and the American Thyroid Association 1, 2, 3, 4, 5, 6, 7, 8
Patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease (ESRD) should not use exenatide and lixisenatide, and caution is advised when using liraglutide and semaglutide in these patients 9, 1
Prior to treatment, patients should be evaluated for personal and family history of medullary thyroid carcinoma and multiple endocrine neoplasia syndrome type 2, and monitored for symptoms such as thyroid nodules, dysphagia, or persistent hoarseness, as recommended by clinical guidelines 2, 6
Patients should be assessed for pheochromocytoma and evaluated for hyperparathyroidism, as recommended by the National Comprehensive Cancer Network 10

The American College of Cardiology recommends using liraglutide with caution in patients with a history of pancreatitis, and exercising caution in patients with prior gastric surgery or severe renal impairment 1
Clinically meaningful gastroparesis may be delayed by shorter-acting GLP-1 RAs, and caution is advised when using GLP-1 RAs in patients with severe gastrointestinal disorders 1

The initial and maintenance doses of GLP-1 receptor agonists are as follows:

Diabetic retinopathy complications, particularly with rapid and marked glucose reductions, have been associated with semaglutide, and patients should be monitored for symptoms of pancreatitis and renal function when initiating or escalating doses of GLP-1 RAs 1, 9
Hypoglycemia risk increases when GLP-1 RAs are combined with insulin or insulin secretagogues, and patients should be monitored for symptoms of hypoglycemia 1
GLP-1 receptor agonists have several potential long-term side effects, including pancreatitis, thyroid C-cell tumors, gallbladder disease, gastrointestinal disorders, and diabetic retinopathy complications, though their cardiovascular and renal benefits often outweigh these risks for most patients, as noted by the American Diabetes Association and European Association for the Study of Diabetes 13

GLP-1 RAs have demonstrated cardiovascular benefits in patients with established cardiovascular disease, with significant reductions in major adverse cardiovascular events (MACE) by 13-26% in patients with type 2 diabetes and established cardiovascular disease, as noted by the American Diabetes Association and European Association for the Study of Diabetes 14
Specific MACE reductions include:
Statins and GLP-1 receptor agonists can be safely co-administered without dose adjustments, as there is no significant interaction between these medication classes, with a strength of evidence supporting this recommendation, as stated by the American College of Cardiology and American Heart Association 16
Patients should be screened for heart failure before initiating GLP-1 RAs, including directed clinical history, physical examination, echocardiogram, and natriuretic peptide measurement, and monitoring of renal function is recommended when initiating or escalating doses of GLP-1 receptor agonists, as recommended by the American Heart Association and European Association for the Study of Diabetes 15, 13