OZEMPIC

Indications

• Type 2 diabetes mellitus
• Weight management in patients with obesity
• Cardiovascular risk reduction in patients with diabetes

Dosage

Adults: Initially 3 mg once daily for 1 month, then increased to 7 mg once daily for at least 1 month, and may be further increased to 14 mg once daily if necessary. Take on an empty stomach.

Mechanism of action

Semaglutide is a GLP-1 analog that binds selectively to the GLP-1 receptor, promoting insulin secretion from pancreatic islet cells in a glucose-dependent manner, slowing gastric emptying, and reducing postprandial glucagon secretion. This multi-faceted approach aids in maintaining glucose homeostasis and offers additional benefits in cardiovascular health and weight management.

Pharmacodynamics

Semaglutide has been shown to significantly reduce HbA1c levels, fasting and postprandial glucose levels, systolic blood pressure, and body weight. It also lowers fasting triglycerides and VLDL cholesterol, contributing positively to cardiovascular health. However, it carries risks of medullary thyroid cell carcinoma and pancreatitis, necessitating caution in patients with certain medical histories.

Pharmacokinetics

Semaglutide exhibits high variability in pharmacokinetics, with a peak plasma concentration typically occurring a few hours after administration. It has a long half-life, allowing for once-daily dosing in oral formulation and once-weekly dosing in injectables. The absorption can be affected by gastric emptying, so monitoring for interaction with other drugs is necessary.

Contra-indications

• Diabetic ketoacidosis
• Personal or family history of medullary thyroid carcinoma
• History of pancreatitis
• Severe congestive heart failure

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain
• Dehydration
• Hypoglycemia
• Pancreatitis
• Weight loss
• Medullary thyroid cell carcinoma (in rodents)

Interactions

• Concomitant insulin or sulfonylureas may require dose adjustments
• Caution with other oral medications due to delayed gastric emptying

Precautions

• Monitor for symptoms of acute pancreatitis (severe abdominal pain)
• Patients must maintain adequate hydration
• Careful blood glucose self-monitoring when initiating therapy

Pregnancy

Avoid - toxicity in animal studies.

Breast-feeding

Avoid - no information available.

Storage

Store in a cool, dry place, protected from light. Follow specific storage instructions provided by the manufacturer.

Formulations

• Oral tablets (3 mg, 7 mg, 14 mg)
• Subcutaneous injection (solution for injection in pre-filled pens)

Mechanism of action

**Mechanism of glycemic control** GLP-1 is a physiological hormone that promotes glycemic control via several different mechanisms, including insulin secretion, slowing gastric emptying, and reducing postprandial glucagon secretion. The homeostasis of glucose is dependent on hormones such as insulin and amylin, which are secreted by the beta cells of the pancreas. Semaglutide is 94% similar to human GLP-1. Analogs of this hormone such as semaglutide stimulate the synthesis of insulin by stimulating pancreatic islet cells and reducing glucagon secretion. They directly bind with selectivity to the GLP-1 receptor, causing various beneficial downstream effects that reduce blood glucose in a glucose-dependent fashion. **Mechanism of cardiovascular benefit and weight loss** In hypercholesterolemia, semaglutide is believed to reduce the progression of atherosclerosis via decreased gut permeability and decreased inflammation. Weight loss is believed to occur via the reduction of appetite and food cravings after semaglutide administration.

Pharmacodynamics

Semaglutide reduces HbA1c, systolic blood pressure, and body weight. After 12 weeks of treatment, semaglutide decreased fasting and postprandial glucose by increasing insulin production and decreasing glucagon secretion (which is normally associated with increases in blood sugar). Semaglutide also lowers fasting triglycerides and VLDL cholesterol, exerting beneficial effects on cardiovascular health. Semaglutide has been shown to cause medullary thyroid cell carcinoma in rodents. While its clinical relevance to humans is unknown, the FDA advises not to administer this drug in those with a personal or family history of medullary thyroid carcinoma. Semaglutide also poses a risk of pancreatitis and dehydration. Patients must be adequately hydrated while on semaglutide and are advised to seek medical attention immediately in cases of abdominal pain radiating to the back. Because this drug delays gastric emptying, it is important to monitor for the efficacy or adverse effects of other drugs that are administered orally.