Semaglutide

Semaglutide is a prescription medication used to treat in combination with a reduced calorie diet and increased physical activity: 

• to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight 
• to reduce excess body weight and maintain weight reduction long term in: 
  • Adults and pediatric patients aged 12 years and older with obesity 
  • Adults with overweight in the presence of at least one weight-related comorbid condition

Semaglutide is available under the following different brand names: Ozempic, Rybelsus, Wegovy.

Adult dosage

Injection, prefilled, single-dose pen (Ozempic)

• 2mg/1.5mL (1.34mg/mL); delivers doses of 0.25mg, 0.5mg, or 1mg per injection
• 4mg/3mL (1.34mg/mL); delivers 1 mg per injection

Injection, prefilled, single-dose pen (Wegovy)

Adult and pediatric dosage

• 0.25mg/0.5mL
• 0.5mg/0.5mL
• 1mg/0.5mL
• 1.7mg/0.75mL
• 2.4mg/0.75mL

Oral tablet (Rybelsus)

• 3mg
• 7mg
• 14mg

Type 2 Diabetes Mellitus

Adult dosage

• SC (Ozempic)
  • 0.25 mg SC once per week for 4 weeks initially; then increase to 0.5 mg per week
  • If glycemic control not achieved after at least 4 weeks on 0.5-mg dose, can increase to 1 mg once weekly
  • Note: the initial 0.25-mg dose is intended for treatment initiation and is not effective for glycemic control
• Oral (Rybelsus)
  • Initial: 3 mg orally once daily for 30 days; then 3-mg dose is intended for treatment initiation and is not effective for glycemic control
  • After 30 days on 3 mg/day: increase to 7 mg orally once daily
  • After 30 days on 7 mg/day: may increase dose to 14 mg orally once daily if additional glycemic control needed
  • Note: Taking two 7-mg tablets to achieve 14 mg dose is not recommended
• Switching between Ozempic (SC) and Ryhelsus (orally)
  • Taking 14 mg/day orally: Transition to 0.5 mg SC once weekly on day after last oral dose
  • Taking 0.5 mg/week SC: Transition to 7 mg or 14 mg orally starting up to 7 days after last SC injection
  • There is no equivalent oral dose for the 1-mg SC dose

Weight Management

Adult dosage

• Wegovy only
  • Initiate with low dose and gradually escalate to maintenance dose of 2.4 mg/week SC to minimize GI adverse reactions
  • If unable to tolerate maintenance dose of 2.4 mg once-weekly, may temporarily decreased to 1.7 mg once weekly, for a maximum of 4 weeks; after 4 weeks, increase back to maintenance 2.4 mg once-weekly; discontinue if not tolerated after second attempt 
    • Weeks 1-4: 0.25 mg
    • Weeks 5-8: 0.5 mg
    • Weeks 9-12: 1 mg
    • Weeks 13-16: 1.7 mg
    • Week 17 onward: 2.4 mg (maintenance)

Pediatric dosage

Wegovy only

• Once weekly SC dose escalation schedule
• Weeks 1-4: 0.25 mg SC every week
• Weeks 5-8: 0.5 mg SC every week
• Weeks 9-12: 1 mg SC every week
• Week 13-16: 1.7 mg SC every week
• Maintenance dosage
  • Week 17 and onward: 2.4 mg SC every week
  • Unable to tolerate maintenance 2.4 mg once-weekly dosage: May reduce maintenance dosage to 1.7 mg SC every week
  • Unable to tolerate 1.7 mg dose: Discontinue treatment

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”.

Common side effects of Semaglutide include:

• nausea, 
• vomiting, 
• stomach pain, 
• loss of appetite, 
• diarrhea, and
• constipation

Serious side effects of Semaglutide include:

• hives, 
• itching, 
• dizziness, 
• fast heartbeats, 
• difficult breathing, 
• swelling of the face, lips, tongue, or throat, 
• vision changes, 
• swelling or a lump in the neck, 
• trouble swallowing,
• hoarse voice, 
• shortness of breath, 
• severe pain in your upper stomach spreading to the back, 
• nausea with or without vomiting, 
• headache,  
• hunger, 
• weakness, 
• sweating, 
• confusion, 
• irritability, 
• dizziness, 
• feeling jittery, 
• little or no urination, 
• swelling in the feet or ankles, and
• tiredness

Rare side effects of Semaglutide include:

• none 

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them.  Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first

• Semaglutide has severe interactions with no other drugs.
• Semaglutide has serious interactions with no other drugs.
• Semaglutide has moderate interactions with at least 22 other drugs.
• Semaglutide has minor interactions with no other drugs.  

This information does not contain all possible interactions or adverse effects.  Visit the RxList Drug Interaction Checker for any drugs interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use.  Keep a list of all your medications with you, and share this information with your doctor and pharmacist.  Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• Personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2
• Known hypersensitivity to Semaglutide or to any of the product components

Effects of drug abuse

• None

Short-Term Effects

• See “What are Side Effects Associated with Using Semaglutide?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Semaglutide?”

Cautions

• Based on findings in rats and mice, Semaglutide may cause thyroid C-cell tumors, including MTC, in humans as human relevance of Semaglutide-induced rodent thyroid C-cell tumors has not been determined
• In control trials, acute pancreatitis was reported (0.3 events [SC] and 0.1 events [PO] per 100 patient years); after initiating treatment, monitor for signs and symptoms of pancreatitis (eg, persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting); if pancreatitis suspected, discontinue Semaglutide and do not restart if confirmed
• Patients treated with Semaglutide showed an increased risk of diabetic retinopathy complications compared with placebo/comparator; rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy
• Semaglutide pens must never be shared between patients, even if the needle is changed; pen-sharing poses a risk for transmission of blood-borne pathogens
• Post-marketing reports describe acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis in patients treated with GLP-1 receptor agonists; a majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration; monitor renal function when initiating or escalating doses of Semaglutide in patients reporting severe adverse GI reactions
• Serious hypersensitivity reactions (eg, anaphylaxis, angioedema) have been reported with GLP-1 receptor agonists; if hypersensitivity reactions occur, discontinue treatment, treat promptly, and monitor until signs and symptoms resolve
• Wegovy only
  • Cholelithiasis reported; substantial or rapid weight loss can increase risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in treated patients than in placebo-treated patients, even after accounting for the degree of weight loss; if suspected, gallbladder studies and appropriate clinical follow-up are indicated
  • Can cause hypoglycemia
  • Heart rate increased (mean 1-4 bpm); 10-19 bpm (41%); 20 bpm (26%)
  • Suicidal behavior and ideation reported in clinical trials with other weight management products; monitor for emergence or worsening depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior; discontinue if suicidal thoughts or behaviors experienced; avoid with history of suicidal attempts/ideation
• Drug interactions overview
  • Coadministration with insulin secretagogues (eg, sulfonylureas) or insulin may increase the risk of hypoglycemia; consider a lower dose of the secretagogue or insulin to reduce risk of hypoglycemia in this setting; inform patients using concomitant medications of risk of hypoglycemia and educate them on signs and symptoms of hypoglycemia
  • Exercise caution when Semaglutide is concomitantly administered with oral medications; Semaglutide causes a delay of gastric emptying, thereby potentially impacting oral absorption of such medications

Pregnancy and Lactation

• Data are insufficient regarding use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
• Based on animal reproduction studies, there may be potential risks to the fetus from exposure to Semaglutide during pregnancy; should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
• Discontinue treatment in women at least 2 months before a planned pregnancy, owing to the long washout period for Semaglutide
• Ozempic, Rybelsus: Use during pregnancy only if potential benefit justifies potential risk to fetus
• Wegovy: Discontinue when pregnancy is recognized; pregnancy registry 1-800-727-6500
• Clinical Considerations
  • Ozempic, Rybelsus
    • Poorly controlled diabetes during pregnancy increases maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications
    • Poorly controlled diabetes increases fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity
  • Wegovy
    • Appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those who already are overweight or obese, because of the obligatory weight gain that occurs in maternal tissues during pregnancy
    • There are no data on the presence of Semaglutide in human milk, the effects on the breastfed infant, or the effects on milk production
    • In lactating rats, Semaglutide was detected in milk at levels 3- to 12-fold lower than in maternal plasm

• There are no data on the presence of Semaglutide in human milk, the effects on the breastfed infant, or the effects on milk production. 

• In lactating rats, Semaglutide was detected in milk at levels 3-to 12-fold lower than in maternal plasma