What is the role of Glucagon-like peptide-1 (GLP-1)?

From the Guidelines

GLP-1 receptor agonists are the preferred treatment for type 2 diabetes management due to their ability to regulate blood sugar, promote weight loss, and offer cardiovascular and kidney benefits, as evidenced by the most recent study in 2024 1.

Key Benefits of GLP-1 Receptor Agonists

• Regulate blood sugar by stimulating insulin release when glucose levels are high
• Promote weight loss through decreased appetite and food intake
• Offer cardiovascular protection by reducing the risk of major adverse cardiovascular events
• Provide kidney benefits by reducing albuminuria and slowing eGFR decline

Common GLP-1 Medications

• Semaglutide (Ozempic, Wegovy)
• Dulaglutide (Trulicity)
• Liraglutide (Victoza, Saxenda)
• Tirzepatide (Mounjaro)

Administration and Dosing

• Subcutaneous injections, either weekly or daily depending on the specific drug
• Dosing typically starts low and increases gradually to minimize gastrointestinal side effects
• For diabetes, semaglutide might begin at 0.25mg weekly for 4 weeks, then increase to 0.5mg weekly

Side Effects

• Nausea, vomiting, diarrhea, and constipation, which often improve over time
• Rare side effects include acute pancreatitis, gallbladder disorders, and cardiac arrhythmia/tachycardia

Clinical Evidence

• The LEADER trial showed a benefit in cardiovascular outcomes with GLP-1 receptor agonists, with a 13% reduction in major adverse cardiovascular events 1
• The SUSTAIN 6 trial confirmed the cardiovascular benefit of GLP-1 receptor agonists, with a 26% reduction in major adverse cardiovascular events 1
• A meta-analysis of 8 cardiovascular outcomes trials found that GLP-1 receptor agonists significantly reduced the risk of a composite kidney disease outcome, including macroalbuminuria, eGFR decline, progression to kidney failure, or death from kidney disease 1

From the FDA Drug Label

OZEMPIC is a glucagon-like peptide 1 (GLP-1) receptor agonist VICTOZA is a glucagon-like peptide-1 (GLP-1) receptor agonist

GLP-1 Receptor Agonists:

• Semaglutide (OZEMPIC) and liraglutide (VICTOZA) are both GLP-1 receptor agonists.
• They are used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus 2, 3.
• They are also indicated to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease 2, 3.

From the Research

Overview of GLP-1

• GLP-1 receptor agonists are a class of injectable glucose-lowering agents that lower A1C with added benefits of weight loss and improved cardiovascular risk markers 4.
• The GLP-1 hormone is partly responsible for insulin release and for attenuating hyperglycemia during meals (ie, the incretin effect) 5.
• GLP-1 receptor agonists exert their effects by improving glucose-dependent insulin release, suppressing glucagon release, suppressing hepatic glucose output, and decreasing the rate of gastric emptying, thereby reducing appetite 5.

Types of GLP-1 Receptor Agonists

• Currently, 5 GLP-1 receptor agonists are available, including exenatide, liraglutide, albiglutide, dulaglutide, and lixisenatide; semaglutide may soon become available as the newest agent 5.
• The choice of a specific GLP-1 receptor agonist will depend on the patient preferences, potential adverse effects, and cost 5.
• GLP-1 receptor agonists can be classified as shorter-acting (exenatide and liraglutide) or longer-acting (exenatide extended-release, dulaglutide, and albiglutide) 4.

Clinical Use of GLP-1 Receptor Agonists

• GLP-1 receptor agonists are recommended as a preferred add-on agent to existing metformin monotherapy, as first-line therapy if metformin is contraindicated or poorly tolerated, and for use in combination with other oral glucose-lowering agents or basal insulin 4.
• GLP-1 receptor agonists have been shown to have beneficial effects on glycemic control, body weight, cardiovascular risk factors, and cardiovascular outcomes 6, 7.
• The combination of a GLP-1 receptor agonist and an SGLT2 inhibitor may provide a complementary approach to the treatment of type 2 diabetes, with potential additive benefits on glycemic control, body weight, and cardiovascular risk factors 7.

Safety and Efficacy of GLP-1 Receptor Agonists

• GLP-1 receptor agonists have a low risk of hypoglycemia, but the incidence of hypoglycemia may be increased when used with insulin secretagogues or insulin 4.
• Gastrointestinal adverse events are common with GLP-1 receptor agonists, but abate over time with continued treatment and are less frequent with longer-acting agents 4.
• Head-to-head clinical studies have demonstrated that all GLP-1 receptor agonists are effective therapeutic options at reducing A1C, but differences exist in terms of magnitude of effect on A1C and weight as well as frequency of adverse effects 8.