From the Guidelines
GLP-1 agonists are a class of medications that mimic the action of glucagon-like peptide-1, a hormone that helps regulate blood sugar levels, and are primarily used to treat type 2 diabetes and, in some cases, obesity, with benefits including weight loss, improved blood sugar control, and reduced risk of major adverse cardiovascular events, as shown in the LEADER trial 1 and SUSTAIN 6 trial 1. These medications work by stimulating insulin release when blood sugar is high, slowing stomach emptying, reducing appetite, and blocking glucagon release (a hormone that raises blood sugar). Common GLP-1 agonists include semaglutide (Ozempic, Wegovy, Rybelsus), dulaglutide (Trulicity), liraglutide (Victoza, Saxenda), exenatide (Byetta, Bydureon), and tirzepatide (Mounjaro). They're typically administered as weekly or daily injections, though some oral formulations exist. Patients using GLP-1 agonists often experience weight loss and improved blood sugar control, with side effects commonly including nausea, vomiting, and diarrhea, which usually improve over time, as noted in the study published in Anaesthesia 1. The American College of Physicians recommends adding a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke, as stated in the clinical guideline published in Annals of Internal Medicine 1. Key benefits of GLP-1 agonists include:
- Weight loss
- Improved blood sugar control
- Reduced risk of major adverse cardiovascular events
- Reduced risk of stroke
- Improved lipid profiles, as shown in the study published in Anaesthesia 1
- Insulin-sparing effect, as demonstrated in the GLOBE study 1 Some potential side effects and management strategies include:
- Nausea and vomiting: avoid in gastroparesis
- Dyspepsia: start GLP-1 receptor agonist at low dose and titrate upward slowly
- Diarrhea: reduce meal size
- Gastrointestinal reflux: limit alcohol and carbonated drinks
- Constipation: avoid high fat diet
- Gallbladder disorders: unusual to be symptomatic
- Cardiac arrhythmia/tachycardia: if symptomatic, monitor and consider beta blockers, as noted in the study published in Anaesthesia 1. Overall, GLP-1 agonists are a valuable tool for managing metabolic conditions, particularly type 2 diabetes, due to their ability to target multiple aspects of blood sugar regulation while promoting satiety, as supported by the evidence from the LEADER trial 1 and SUSTAIN 6 trial 1.
From the FDA Drug Label
OZEMPIC is a glucagon-like peptide 1 (GLP-1) receptor agonist indicated as: • an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (1). • to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease (1)
GLP-1 receptor agonists, such as semaglutide, improve glycemic control and reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus.
- They are used as an adjunct to diet and exercise to improve glycemic control.
- They are also used to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease 2.
From the Research
Mechanisms of Action
- GLP-1 receptor agonists (GLP-1 RAs) work by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion, decelerating gastric emptying, and reducing calorie intake and body weight 3, 4, 5.
- They improve glucose-dependent insulin release, suppress glucagon release, suppress hepatic glucose output, and decrease the rate of gastric emptying, thereby reducing appetite 5.
Effects on Glycemic Control
- GLP-1 RAs have been shown to reduce hemoglobin A1c, fasting blood glucose, and body weight both as monotherapy and in combination with other diabetes agents 3, 4, 5.
- Long-acting GLP-1 RAs have more profound effects on overnight and fasting plasma glucose and HbA1c compared to short-acting agents 3.
- Semaglutide, a long-acting GLP-1 RA, has been shown to reduce HbA1c by 1.01% and 1.38% at doses of 0.5 and 1 mg, respectively, compared to placebo 6.
Cardiovascular and Kidney Benefits
- GLP-1 RAs have been shown to reduce the incidence of major adverse cardiovascular events (MACE) by 14% and hospitalization for heart failure by 14% 7.
- They also reduce the incidence of a composite kidney outcome by 17% and all-cause mortality by 12% 7.
- Long-acting GLP-1 RAs, including both injectable and oral formulations, reduce the incidence of MACE, hospitalization for heart failure, and kidney events and all-cause mortality in type 2 diabetes 7.
Safety and Tolerability
- GLP-1 RAs are generally well-tolerated, with the most common adverse events being mild or moderate in nature, including transient nausea, vomiting, and diarrhea 3, 4, 6.
- Long-acting agents have lower rates of nausea but an increased incidence of injection site reactions 4.
- There is no significant increase in the risk of severe hypoglycemia, retinopathy, or pancreatic events with GLP-1 RAs 7.