GLP-1 Receptor Agonists: Available Agents
GLP-1 receptor agonists are a class of injectable (and now oral) medications for type 2 diabetes that include both short-acting agents (exenatide twice daily, lixisenatide once daily) and long-acting agents (liraglutide once daily, semaglutide once weekly, dulaglutide once weekly, exenatide once weekly, and albiglutide once weekly). 1, 2, 3
Short-Acting GLP-1 Receptor Agonists
These agents primarily work by delaying gastric emptying and lowering postprandial glucose:
- Exenatide (twice daily) - The first GLP-1 receptor agonist approved in 2007, derived from exendin-4 found in Gila monster venom 2, 4
- Lixisenatide (once daily) - A short-acting agent that has been studied in cardiovascular outcomes trials 1, 5
Long-Acting GLP-1 Receptor Agonists
These agents affect both fasting and postprandial glucose through enhanced insulin secretion and reduced glucagon secretion:
- Liraglutide (once daily) - Has demonstrated cardiovascular benefit and mortality reduction in large cardiovascular outcomes trials, with particularly strong benefits in patients with chronic kidney disease 1, 6, 2
- Semaglutide (once weekly injectable and oral formulation) - Available as both subcutaneous injection and the first oral GLP-1 receptor agonist preparation, with demonstrated cardiovascular benefits 1, 2, 4
- Dulaglutide (once weekly) - Has shown cardiovascular and kidney benefits in outcomes trials, including slower GFR decline compared to insulin glargine in patients with moderate-to-severe CKD 1, 2, 4
- Exenatide (once weekly) - A long-acting formulation of exenatide with improved tolerability compared to the twice-daily version 1, 5, 7
- Albiglutide (once weekly) - Demonstrated cardiovascular benefits but is not currently available on the market 1, 2, 4
Investigational Agent
- Efpeglenatide - Has been studied in cardiovascular outcomes trials but is not yet widely available 1
Dual GIP/GLP-1 Receptor Agonist
- Tirzepatide (once weekly) - A newer agent that activates both GIP and GLP-1 receptors, producing greater reductions in HbA1c and body weight compared to selective GLP-1 receptor agonists like semaglutide and dulaglutide 8
Preferred Agents Based on Outcomes
The GLP-1 receptor agonists with proven cardiovascular and kidney benefits—liraglutide, semaglutide, and dulaglutide—are the preferred agents, particularly in patients with established cardiovascular disease or chronic kidney disease. 1 These three agents have demonstrated reduction in major adverse cardiovascular events (MACE) in large cardiovascular outcomes trials, with liraglutide additionally showing reductions in cardiovascular and all-cause mortality 1, 2