Semaglutide is a glucagon-like peptide 1 receptor agonist used to improve glycemic control in type 2 diabetes mellitus.
Semaglutide is indicated for chronic weight management in adults with obesity or overweight with at least one weight-related condition (such as high blood pressure, type 2 diabetes, or high cholesterol), for use in addition to a reduced-calorie diet and increased physical activity. Semaglutide it is also indicated for chronic weight management in pediatric patients aged 12 years and older with an initial BMI at the 95th percentile or greater for age and sex.
Semaglutide is a glucagon-like peptide 1 (GLP-1) analog used to manage type 2 diabetes along with lifestyle changes, such as dietary restrictions and increased physical activity. Other members of this drug class include Exenatide and Liraglutide.
An early study of 2,000 obese adults compared people using semaglutide plus a diet and exercise program with people who made the same lifestyle changes without semaglutide. After 68 weeks, half of the participants using semaglutide lost 15% of their body weight, and nearly a third lost 20%.
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.
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 insulin3 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.
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.
Metabolism: Semaglutide is cleaved at the peptide backbone, followed by β‐oxidation of the fatty acid chain. Naturally occurring GLP‐1 is quickly metabolized by dipeptidyl peptidase‐4 (DPP‐4) and other enzymes, which is ubiquitous in human tissues. Chemical structure modifications render semaglutide less susceptible to enzymatic degradation by gastrointestinal DPP‐4 enzymes.11 It is slowly and extensively metabolized, with about 83% of the administered dose measured in the plasma as unchanged drug.
Absorption: The Cmax of semaglutide was 10.9 nmol/L, with AUC of 3123. nmol h/L and a Tmax of 56 h in one clinical trial, achieved within 1-3 days. The absolute bioavailability is 89%. Steady-state concentration of the oral tablet is achieved in 4-5 weeks. Average steady state concentrations of semaglutide are the mean steady state concentrations after dosing at 0.5mg to 1mg range from 16 nmol/L to 30 nmol/L.
Route of elimination: This drug is mainly cleared by the kidneys, and is found excreted in both the urine and feces.11 The main elimination route is the urine by corresponding to 53% of an ingested radiolabeled dose, with 18.6% found in the feces. A smaller amount of 3.2% was found to be exhaled.
Half life: One of the major properties of semaglutide is its long half-life of 168 h. The long half-life is attributed to its albumin binding. This lowers the renal clearance and protects semaglutide from metabolic breakdown.
All medicines may cause side effects, but many people have no, or minor, side effects. Some medical conditions may interact with Semaglutide.
Tell your doctor or pharmacist if you have any medical conditions.
Overdoses of up to 4 mg in one ingestion have been reported, with nausea being the most commonly reported symptom. All patients in clinical trials who experienced an overdose recovered fully. Appropriate supportive care should be given according and dictated by the patient's condition. Prolonged observation and treatment may be required, as the half-life of this drug is about one week. There is no antidote to an overdose with semaglutide.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.
