Switching Between Glucagon-Like Peptide-1 Receptor Agonists: Rationale and Practical Guidance

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of incretin-based therapies for the management of hyperglycemia and, in some cases, cardiovascular risk in people with type 2 diabetes. These agents act on multiple physiological pathways involved in type 2 diabetes with the effect of increasing insulin secretion and decreasing glucagon to control glucose levels (1,2). They also transiently slow gastric emptying, reduce appetite, and facilitate weight loss and other metabolic improvements (3). Consensus recommendations from the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) and American Association of Clinical Endocrinologists/American College of Endocrinology advocate that GLP-1 receptor agonists, among other therapies, should be considered as a second-line treatment option in people with type 2 diabetes when glucose levels are not well controlled on metformin (4–6). Additionally, in patients with type 2 diabetes and atherosclerotic cardiovascular disease or chronic kidney disease, a GLP-1 receptor agonist or sodium–glucose cotransporter 2 (SGLT2) inhibitor with proven cardiovascular benefit is recommended as a first-line therapy for the reduction of cardiovascular risk (4–6). GLP-1 receptor agonists may also be used as a first-line treatment in those who cannot use metformin or when reduced renal function precludes metformin use (human-based GLP-1 receptor agonists only) (4–6). In particular, the recommendations favor GLP-1 receptor agonists and SGLT2 inhibitors because they have a low risk of hypoglycemia and promote weight loss (5). Several GLP-1 receptor agonists are available in the United States and worldwide, some of which are analogs of human GLP-1 (dulaglutide, liraglutide, and semaglutide), whereas others are exendin-based (exenatide and lixisenatide) (7–13). The GLP-1 receptor agonist albiglutide was also approved, but has been withdrawn for commercial reasons. Until recently, all GLP-1 receptor agonists were administered by subcutaneous injection, although a once-daily oral formulation …