Semaglutide

# semaglutide ## Overview - **Classification**: Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist - **Mechanism**: Mimics endogenous GLP-1 to increase glucose-dependent insulin secretion, decrease glucagon secretion, slow gastric emptying, and promote satiety. ## Primary Indications 1. **Type 2 Diabetes Mellitus**: To improve glycemic control in adults. 2. **Cardiovascular Risk Reduction**: To reduce the risk of major adverse cardiovascular events (MACE) in adults with T2DM and established CV disease. 3. **Chronic Weight Management**: In adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity. ## Adult Dosing ### Standard Dosing **Type 2 Diabetes Mellitus & CV Risk Reduction (Ozempic - SC; Rybelsus - Oral)** - **Ozempic (subcutaneous injection)**: - **Initiation**: **0.25 mg** once weekly for 4 weeks. - **Escalation**: Increase to **0.5 mg** once weekly. - **Further Escalation**: May increase to **1 mg** once weekly after ≥4 weeks on 0.5 mg. - **Max Dose**: May increase to **2 mg** once weekly after ≥4 weeks on 1 mg. - **Frequency**: Once weekly. - **Route**: Subcutaneous. - **Rybelsus (oral tablet)**: - **Initiation**: **3 mg** once daily for 30 days. - **Escalation**: Increase to **7 mg** once daily. - **Further Escalation**: May increase to **14 mg** once daily after ≥30 days on 7 mg. - **Max Dose**: **14 mg** once daily. - **Frequency**: Once daily. - **Route**: Oral (take on empty stomach with ≤4 oz water, 30 min before food/drink/other oral meds). **Chronic Weight Management (Wegovy - SC)** - **Wegovy (subcutaneous injection)**: - **Initiation**: **0.25 mg** once weekly for 4 weeks. - **Escalation**: Gradually increase dose every 4 weeks over 16 weeks as tolerated. - **Dose Schedule**: **0.25 mg**, **0.5 mg**, **1 mg**, **1.7 mg**, then **2.4 mg** (maintenance). - **Max Dose**: **2.4 mg** once weekly. - **Frequency**: Once weekly. - **Route**: Subcutaneous. ### Dose Adjustments - **Renal Impairment**: No dose adjustment needed; use with caution in ESRD due to limited experience. - **Hepatic Impairment**: No dose adjustment needed. - **Elderly Patients**: No dose adjustment needed based on age. Monitor for dehydration due to GI side effects. ## Pediatric Dosing *Note: Ozempic and Rybelsus are **not indicated** for pediatric patients. Wegovy is approved for adolescents ≥12 years for chronic weight management.* ### Neonates (0-28 days) - **Not indicated.** ### Infants (1-12 months) - **Not indicated.** ### Children (1-12 years) - **Not indicated** for Type 2 Diabetes. - **Wegovy for Chronic Weight Management (12 years and older)**: - **Dose**: Start with **0.25 mg** SC once weekly. - **Frequency**: Once weekly. - **Escalation**: Follow adult escalation schedule, increasing dose every 4 weeks. - **Maximum**: **2.4 mg** once weekly. - **Special Notes**: Monitor for dehydration, especially with GI adverse effects. ### Adolescents (13-18 years) - **Wegovy for Chronic Weight Management (12 years and older)**: - **Dose**: Same as children 12 years and older, following the adult escalation schedule. - **Frequency**: Once weekly. - **Maximum**: **2.4 mg** once weekly. - **Special Notes**: Consider discontinuing if unable to tolerate maintenance dose or if insufficient weight loss after 12 weeks. ## Safety Information ### Contraindications - **Absolute**: Personal or family history of **Medullary Thyroid Carcinoma (MTC)**. - **Absolute**: Patients with Multiple Endocrine Neoplasia syndrome type 2 (**MEN 2**). - **Absolute**: Prior severe hypersensitivity reaction to semaglutide or excipients. - **Absolute**: Pregnancy (discontinue at least 2 months prior to conception). - **Absolute**: Type 1 Diabetes Mellitus or Diabetic Ketoacidosis (not indicated). - **Absolute**: Wegovy (obesity indication) in patients with a history of **pancreatitis**. ### Common Adverse Effects - **Very Common (>10%)**: Nausea, Diarrhea, Vomiting, Constipation, Abdominal pain. - **Common (1-10%)**: Dyspepsia, Headache, Fatigue, Dizziness, Hypoglycemia (with insulin/sulfonylurea). - **Serious but Rare**: Pancreatitis, Gallbladder disease (cholelithiasis, cholecystitis), Thyroid C-cell tumors (rodent data), Acute kidney injury, Anaphylaxis/Angioedema, Diabetic Retinopathy complications. ### Key Drug Interactions - **Insulin & Sulfonylureas**: Increased risk of hypoglycemia. - **Monitoring**: Close glucose monitoring. - **Dose adjustment needed**: May require dose reduction of insulin or sulfonylurea. - **Oral Medications (Rybelsus)**: Delayed gastric emptying can alter absorption of co-administered oral drugs. - **Monitoring**: Adherence to Rybelsus administration instructions. - **Clinical Significance**: Take other oral medications at least 30 minutes after Rybelsus. - **Warfarin**: Potential for altered INR due to delayed gastric emptying. - **Monitoring**: Frequent INR monitoring upon initiation or dose change. - **Dose adjustment needed**: Warfarin dose may need adjustment. ## Monitoring & Follow-up - **Before Treatment**: Assess history of MTC/MEN 2; baseline renal function; pregnancy test for women of childbearing potential (Wegovy). - **During Treatment**: - Monitor for symptoms of pancreatitis (severe abdominal pain), gallbladder disease (RUQ pain). - Monitor for signs/symptoms of thyroid tumors (neck mass, dysphagia, hoarseness). - Monitor for acute kidney injury, especially with severe GI adverse events/dehydration. - Glycemic control (HbA1c) for T2DM; weight/BMI for weight management. - Glucose monitoring for hypoglycemia, especially if on insulin/sulfonylurea. - **Clinical Signs**: Watch for persistent severe abdominal pain, unexplained nausea/vomiting, yellowing skin/eyes, neck lump, severe allergic reactions. ## Clinical Pearls - 💡 **Rybelsus Administration**: Take oral semaglutide (Rybelsus) first thing in the morning with a sip of plain water (≤4 oz), at least **30 minutes before** any food, drink, or other oral medications. - 💡 **Injection Technique**: Rotate subcutaneous injection sites weekly (abdomen, thigh, or upper arm). - 💡 **Titration Importance**: Gradual dose escalation is critical to minimize common gastrointestinal side effects. Counsel patients on managing these effects and staying hydrated. - 💡 **Pregnancy Planning**: Due to its long half-life, women of childbearing potential should discontinue semaglutide at least 2 months prior to a planned pregnancy. - 💡 **Black Box Warning**: Semaglutide has a boxed warning regarding the risk of thyroid C-cell tumors (MTC) observed in rodent studies. The relevance to humans is unknown. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.