From the Guidelines
GLP-1 medications work by mimicking the action of glucagon-like peptide-1, a natural hormone that regulates blood sugar, and their mechanism of action involves stimulating insulin release, reducing glucagon secretion, slowing gastric emptying, and increasing feelings of fullness, as evidenced by the most recent study in 2025 1.
Key Mechanisms of Action
- Stimulate insulin release from the pancreas when blood sugar is high
- Reduce glucagon secretion, which normally raises blood sugar
- Slow gastric emptying to delay glucose absorption
- Increase feelings of fullness by acting on the brain's appetite center These effects help lower blood sugar levels, reduce appetite, and often lead to weight loss, as supported by studies such as 1 and 1.
Administration and Usage
GLP-1 medications are typically administered as subcutaneous injections, with dosing frequencies ranging from daily to weekly depending on the specific medication, such as semaglutide (Ozempic, Wegovy), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), and tirzepatide (Mounjaro) 1. They're primarily used for type 2 diabetes management but some are also approved for weight management.
Clinical Implications
The use of GLP-1 medications has been shown to improve glycaemic control and reduce the risk of major adverse cardiovascular events, as well as promote significant weight loss, making them a valuable treatment option for patients with type 2 diabetes and obesity, as highlighted in the 2025 consensus statement 1. However, their use in the peri-operative setting requires careful consideration due to potential risks such as pulmonary aspiration, and guidelines recommend individualized management taking into account drug characteristics, patient profile, and procedure-specific factors 1.
From the FDA Drug Label
Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.
GLP-1 medications, such as semaglutide, work by:
- Stimulating insulin secretion in a glucose-dependent manner
- Lowering glucagon secretion in a glucose-dependent manner
- Causing a minor delay in gastric emptying in the early postprandial phase This results in lowering blood glucose concentrations, with effects on both fasting and postprandial glucose levels 2.
From the Research
Mechanism of Action
- GLP-1 receptor agonists (GLP-1 RAs) work by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion at hyper- or euglycemia, decelerating gastric emptying, and reducing calorie intake and body weight 3, 4
- The primary pharmacodynamic difference between short-acting and long-acting GLP-1 RAs is that short-acting agents primarily delay gastric emptying, while long-acting agents affect both fasting glucose and postprandial glucose 4
Effects on Glycemic Control and Weight Loss
- GLP-1 RAs have been shown to be effective in reducing HbA1c levels and promoting weight loss in patients with type 2 diabetes 3, 5
- Long-acting GLP-1 RAs, such as semaglutide and liraglutide, have been found to have more profound effects on overnight and fasting plasma glucose and HbA1c levels compared to short-acting agents 3
Administration and Tolerability
- GLP-1 RAs can be administered via injection (twice daily, once daily, or once weekly) or orally (in the case of oral semaglutide) 3, 5
- The tolerability profile of GLP-1 RAs is generally consistent with that of other glucose-lowering therapies, with gastrointestinal side effects being the most common 5
Cardiovascular Benefits
- GLP-1 RAs have been shown to have cardioprotective effects, including reducing the risk of cardiovascular events such as acute myocardial infarction or stroke and associated mortality 3, 6
- The mechanisms of cardioprotection achieved by GLP-1 RAs are not fully understood but may include improvements in glycemic control, weight loss, and anti-inflammatory effects 6