How does Ozempic (semaglutide) work in the human body?

From the Guidelines

Ozempic (semaglutide) works by mimicking a hormone called GLP-1 (glucagon-like peptide-1) that naturally occurs in the body, stimulating insulin release, reducing glucagon secretion, slowing gastric emptying, and increasing feelings of fullness to improve glycemic control and promote weight loss. When injected subcutaneously once weekly at doses ranging from 0.25 mg to 2 mg, this medication primarily helps control blood sugar in people with type 2 diabetes while also promoting weight loss 1. The mechanisms of action of Ozempic include:

• Stimulating insulin release from the pancreas when blood sugar is high
• Reducing excessive glucagon secretion (a hormone that raises blood sugar)
• Slowing gastric emptying to delay glucose absorption
• Acting on the brain's appetite center to increase feelings of fullness and reduce hunger These combined effects lead to improved glycemic control and reduced caloric intake. The medication begins working shortly after injection but may take several weeks to reach its full therapeutic effect. Common side effects include nausea, vomiting, and diarrhea, which often improve over time as the body adjusts to the medication 1. Patients should start at the lowest dose (0.25 mg weekly) for four weeks before gradually increasing to minimize these gastrointestinal effects. It is also important to consider the potential risks and benefits of Ozempic in different patient populations, such as those with cardiovascular disease or obesity 1. Overall, Ozempic is a valuable treatment option for people with type 2 diabetes and obesity, offering improved glycemic control and weight loss benefits 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. GLP-1 is a physiological hormone that has multiple actions on glucose, mediated by the GLP-1 receptors The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilized against degradation by the DPP-4 enzyme Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated, and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.

Ozempic (semaglutide) works in the human body by:

• Stimulating insulin secretion in a glucose-dependent manner
• Lowering glucagon secretion in a glucose-dependent manner
• Delaying gastric emptying in the early postprandial phase
• Binding to and activating the GLP-1 receptor, which has multiple actions on glucose 2

From the Research

Mechanism of Action of Ozempic (Semaglutide)

• Ozempic (semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist that works by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion, decelerating gastric emptying, and reducing calorie intake and body weight 3.
• Semaglutide has been shown to have a more profound effect on overnight and fasting plasma glucose and HbA1c compared to short-acting GLP-1 receptor agonists 3.
• The medication is available in both subcutaneous and oral dosage forms and has been approved as a second-line treatment option for better glycemic control in type 2 diabetes 4.

Efficacy and Safety of Semaglutide

• Clinical trials have demonstrated the efficacy and safety of semaglutide in patients with type 2 diabetes, with significant reductions in HbA1c and body weight compared to placebo and other antidiabetic agents 5, 6.
• Semaglutide has also been shown to have cardiovascular benefits, reducing the risk of major adverse cardiovascular events such as acute myocardial infarction or stroke and associated mortality 3, 4.
• The medication is generally well-tolerated, but may cause gastrointestinal adverse effects such as nausea, vomiting, and diarrhea 6.

Real-World Evidence and Comparisons

• A real-world study found that switching from dulaglutide to semaglutide was associated with an additional reduction in HbA1c and weight, without significant changes in adverse effects 7.
• Semaglutide has been compared to other GLP-1 receptor agonists, such as liraglutide and dulaglutide, and has been shown to have superior glycemic efficacy and weight loss benefits 5, 6.