From the Guidelines
Semaglutide is a highly effective medication for managing type 2 diabetes, offering significant benefits in blood glucose control, weight loss, and cardiovascular risk reduction, as evidenced by the most recent and highest quality study 1.
Key Benefits of Semaglutide
- Improves blood glucose control by stimulating insulin secretion, suppressing glucagon release, slowing gastric emptying, and reducing appetite
- Promotes weight loss, which is beneficial for most type 2 diabetes patients
- Offers cardiovascular benefits, reducing the risk of major adverse cardiovascular events, as shown in the SUSTAIN-6 trial 1 and other studies 1
- Available as a once-weekly injection (Ozempic) or daily oral tablet (Rybelsus), with flexible dosing regimens to minimize gastrointestinal side effects
Important Considerations
- Common side effects include nausea, vomiting, and diarrhea, which typically improve over time
- Patients should start at the lowest dose and gradually increase to minimize gastrointestinal effects
- Semaglutide should not be used in patients with personal or family history of medullary thyroid carcinoma or in those with Multiple Endocrine Neoplasia syndrome type 2
- GLP-1 receptor agonists, including semaglutide, have shown kidney benefits, reducing albuminuria and slowing eGFR decline, as reported in a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1
Clinical Use
- Semaglutide is a preferred agent for managing type 2 diabetes, particularly in patients with established cardiovascular disease or at high risk of cardiovascular events
- The medication should be used in conjunction with lifestyle modifications, such as diet and exercise, to achieve optimal blood glucose control and cardiovascular risk reduction
- Healthcare providers should closely monitor patients for potential side effects and adjust the dosing regimen as needed to minimize gastrointestinal effects and ensure optimal therapeutic outcomes.
From the FDA Drug Label
Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Semaglutide lowers fasting and postprandial blood glucose and reduces body weight. In patients with type 2 diabetes, treatment with semaglutide 1 mg resulted in reductions in glucose in terms of absolute change from baseline and relative reduction compared to placebo of 29 mg/dL (22%) for fasting glucose, 74 mg/dL (36%) for 2-hour postprandial glucose, and 30 mg/dL (22%) for mean 24-hour glucose concentration.
Semaglutide's role in managing type 2 diabetes is to:
- Stimulate insulin secretion
- Lower glucagon secretion
- Reduce blood glucose levels, including fasting and postprandial glucose
- Reduce body weight Semaglutide achieves these effects through a glucose-dependent mechanism, meaning it only stimulates insulin secretion and lowers glucagon secretion when blood glucose is high 2.
From the Research
Role of Semaglutide in Managing Type 2 Diabetes
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, plays a significant role in managing type 2 diabetes. The key aspects of its role include:
- Improved glycemic control: Semaglutide achieves greater reduction from baseline in HbA1c compared to placebo, with a greater proportion of patients achieving target HbA1c levels 3.
- Weight loss: Semaglutide contributes to reduced body weight and improves obesity-related complications, making it beneficial for diabetic patients with high cardiovascular risk 3, 4.
- Cardiovascular benefits: Semaglutide has been shown to reduce the occurrence of cardiovascular events in patients at high risk of cardiovascular disease, with a hazard ratio of 0.74 compared to placebo/standard of care 4.
Mechanism of Action
Semaglutide works via the incretin pathway, stimulating insulin and inhibiting glucagon secretion from the pancreatic islets, leading to lower blood glucose levels. It also decreases energy intake by reducing appetite and food cravings, and lowering relative preference for fatty, energy-dense foods 4.
Efficacy and Safety
Studies have demonstrated the efficacy and safety of semaglutide in patients with type 2 diabetes. The SUSTAIN clinical trial program showed that semaglutide consistently demonstrated superior and sustained glycemic control and weight loss compared to all comparators evaluated 4. Additionally, semaglutide has been shown to have a similar safety profile to other GLP-1 receptor agonists, with mostly mild-to-moderate and transient gastrointestinal disturbances, and an increased risk of biliary disease (cholelithiasis) 5.
Dosage and Administration
Semaglutide is available as a once-weekly subcutaneous injection, and a higher dose of 2.0 mg has been shown to be superior to 1.0 mg in reducing HbA1c, with additional body weight loss and a similar safety profile 6. Semaglutide has also been approved as an oral dosage form, making it a convenient option for patients with type 2 diabetes 7.