From the Guidelines
Semaglutide is a GLP-1 receptor agonist that works by mimicking the action of the naturally occurring hormone GLP-1 in the body, leading to improved glycemic control and significant weight loss. Semaglutide is available under brand names like Ozempic, Wegovy, and Rybelsus, with varying doses depending on the specific indication (diabetes management or weight loss). It's typically administered as a once-weekly subcutaneous injection or as a daily oral tablet. As a GLP-1 receptor agonist, semaglutide binds to and activates GLP-1 receptors, primarily in the pancreas and brain. This activation leads to several beneficial effects:
- Increased insulin secretion in response to elevated blood glucose
- Decreased glucagon secretion
- Slowed gastric emptying
- Increased satiety and reduced appetite These mechanisms contribute to improved glycemic control in diabetes patients and significant weight loss in individuals with obesity, as demonstrated in studies such as the STEP trials 1. It's essential to note that semaglutide does not inhibit or block any receptors or enzymes; rather, it enhances the body's natural GLP-1 signaling pathway. When prescribing or using semaglutide, start with a low dose and gradually increase to minimize gastrointestinal side effects, as recommended in the study by 1. Always follow the specific dosing instructions for the particular formulation being used. The most recent and highest-quality study, 1, provides further evidence of the efficacy and safety of semaglutide in improving cardiovascular outcomes in patients with type 2 diabetes.
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.
The mechanism of action of Semaglutide (Ozempic) is through its action as a GLP-1 receptor agonist, which:
- Stimulates insulin secretion in a glucose-dependent manner
- Lowers glucagon secretion in a glucose-dependent manner
- Causes a minor delay in gastric emptying in the early postprandial phase 2
From the Research
Mechanism of Action of Semaglutide
The mechanism of action of Semaglutide, a Glucagon-like peptide-1 (GLP-1) receptor agonist, can be understood through its effects on glucose metabolism and weight loss. Key aspects include:
- Semaglutide is injected subcutaneously once a week for the treatment of Type 2 diabetes, promoting sustained improved glycaemic control and weight loss compared to other treatments 3.
- It works by agonizing the GLP-1 receptor, which is involved in glucose-dependent insulin secretion, glucagon secretion, and appetite regulation 4, 5.
- The efficacy of semaglutide in reducing HbA1c levels and body weight has been demonstrated in several clinical trials, including the PIONEER programme, which tested oral semaglutide in patients with Type 2 diabetes 6.
- Semaglutide has a half-life of 7 days, allowing it to reach steady state in 4-5 weeks, with few drug interactions and no necessary dose adjustments 7.
Clinical Implications
The clinical implications of semaglutide's mechanism of action include:
- Improved glycaemic control: Semaglutide has been shown to reduce HbA1c levels by 1.5-1.9% after 30-56 weeks of treatment 7.
- Weight loss: Semaglutide has resulted in a 5-10% weight reduction from baseline in clinical efficacy studies 7.
- Cardiovascular benefits: Semaglutide has been proven to reduce various cardiovascular risk factors in patients with established cardiovascular disorders 4.
- Low risk of hypoglycemia: Semaglutide is well tolerated with no risk of hypoglycemia in monotherapy, making it a suitable option for patients with Type 2 diabetes 4, 6.