Glucagon-Like Peptide 1 Receptor Agonists for Type 2 Diabetes

Abstract

The incretin system has become an important target in the treatment of type 2 diabetes in recent years, and glucagon-like peptide 1 (GLP-1) is of particular interest for its glucose-lowering effects. The physiological response to oral ingestion of nutrients, involving the incretin system, is reduced in some patients with type 2 diabetes but may be augmented by administration of GLP-1 receptor agonists. The GLP-1 receptor agonists currently approved in the United States for the treatment of type 2 diabetes include exenatide (administered twice daily), liraglutide and lixisenatide (administered once daily), and the once-weekly agents exenatide extended-release, albiglutide, and dulaglutide. These agents have been shown to reduce A1C (by ∼0.8-1.6%), body weight (by ∼1-3 kg), blood pressure, and lipids. GLP-1 receptor agonists are associated with a low risk of hypoglycemia, and the most common adverse effects are gastrointestinal. Proper patient selection and education can assist in achieving positive treatment outcomes.

FIGURE 1.

Actions of GLP-1 in target tissues. Adapted with permission from ref. 9. GI, gastrointestinal.

FIGURE 2.

Range of mean changes from baseline in A1C in clinical studies of 24–52 weeks’ duration reported in prescribing information for five GLP-1 receptor agonists (–18). Each square represents the finding from one study. Drugs were tested as monotherapy or in combination with oral medications except as noted. *Finding reported as comparator in clinical study in another drug’s prescribing information. †Finding for drug in combination with insulin. QD, once daily.

FIGURE 3.

Range of mean changes from baseline in body weight in clinical studies of 24–52 weeks’ duration reported in prescribing information for five GLP-1 receptor agonists (–18). Each square represents findings from one study. Drugs were tested as monotherapy or in combination with oral medications except as noted. *Finding reported as comparator in clinical study in another drug’s prescribing information. †Finding for drug in combination with insulin. QD, once daily.