Semaglutide

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

• to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) (Ozempic, Rybelsus)
• to reduce the risk of major adverse cardiovascular (CV) events (MACE) (CV death, non-fatal myocardial infarction, or non-fatal stroke:
  • in adults with T2DM and established CV disease (Ozempic)
  • in adults with established CV disease and either obesity or overweight (Wegovy)
• to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease, and cardiovascular death in adults with T2DM and chronic kidney disease (CKD) (Ozempic)
• to reduce excess body weight and maintain weight reduction long-term in (Wegovy):
  • 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
• for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) in adults (Wegovy).

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

Adult and pediatric dosage

Injection, prefilled, single-dose pen (Ozempic)

• 2 mg/1.5 mL (1.34 mg/mL); delivers doses of 0.25mg, 0.5mg, or 1mg per injection
• 4 mg/3 mL (1.34 mg/mL); delivers 1 mg per injection
• 8 mg/3 mL (2.68 mg/mL); delivers 2 mg per injection

Injection, prefilled, single-dose pen (Wegovy)

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

Oral oval tablet, formulation R1 (Rybelsus)

• 3 mg
• 7 mg
• 14 mg

Oral round tablet, formulation R2 (Rybelsus)

• 1.5 mg
• 4 mg
• 9 mg

Type 2 Diabetes Mellitus

Adult dosage

• SC (Ozempic)
• SC dosage initiation
  • 0.25 mg SC once weekly x 4 weeks
  • After 4 weeks, it increases to 0.5 mg once weekly
• SC maintenance dosage for glycemic control
  • Recommended maintenance dosage is 0.5 mg, 1 mg, or 2 mg SC once weekly, based on glycemic control
  • If additional glycemic control is needed after at least 4 weeks, may increase as follows
  • Taking 0.5 mg/week: May increase to 1 mg/week
  • Taking 1 mg/week: May increase to 2 mg/week
  • Maximum recommended dose: 2 mg/week
• SC maintenance dosage for patients with T2DM and CKD
  • After at least 4 weeks on 0.5 mg/week, increase to the maintenance dose of 1 mg/week
• Oral (Rybelsus)
• Oral dosage
  • There are 2 formulations (ie, formulation R1 and formulation R2) with different recommended dosages
  • Refer to recommendations on how to switch from one formulation to another formulation
  • Rybelsus (formulation R1) includes strengths 3 mg, 7 mg, and 14 mg
  • Rybelsus (formulation R2) includes strengths 1.5 mg, 4 mg, and 9 mg
  • Formulations are not substitutable on a mg per mg basis
  • Use either formulation R1 or formulation R2; do NOT use both formulations simultaneously
  • Do NOT take more than 1 tablet per day
  • To reduce the risk of gastrointestinal (GI) adverse effects, follow the recommended initiation, escalation, and maintenance dosing regimens for R1 and R2 formulations
• Formulation R1 dose
  • Initiaion phase (Days 1-30): 3 mg orally daily for 30 days; this dose is not effective for glycemic control
  • Days 31-60: Increase to 7 mg orally daily
  • Day 61 and thereafter: Maintain dose at 7 mg/day, or may increase to 14 mg orally daily if additional glycemic control is needed
  • Note: Taking two 7-mg tablets to achieve a 14 mg dose is not recommended
• Formulation R2 dose
  • Initiation phase (Days 1-30): 1.5 mg orally daily; this dose is not effective for glycemic control
  • Days 31-60: Increase to 4 mg orally daily
  • Day 61 and thereafter: Maintain dose at 4 mg/day, or may increase to 9 orally daily if additional glycemic control is needed
• Switching between the Rybelus formulation
  • Do not switch during the initiation phase (Days 1-30)
  • If switching between formulations R1 and R2, discontinue the current formulation and initiate the alternate formulation the next day
  • May switch between formulation R1 (7 mg) and formulation R2 (4 mg)
  • May switch between formulation R1 (14 mg) and formulation R2 (9 mg)
• Switching from Ozempic (SC) to Rybelsus (orally)
  • Switching to formulation R1: 1 week after discontinuing 0.5 mg SC, start 7 mg or 14 mg orally daily
  • Switching to formulation R2: 1 week after discontinuing 0.5 mg SC, start 4 mg or 9 mg orally daily
  • Recommendations are unavailable if taking Ozempic 0.25 mg, 1 mg, or 2 mg SC weekly
• Weight Management
• Adult and pediatric dosage
• Wegovy only
  • Dosage
    • Initiate with a low dose and gradually escalate to a maintenance dose of 2.4 mg/week SC to minimize GI adverse reactions
    • If unable to tolerate a dose during escalation, consider delaying dose escalation for 4 weeks
    • If unable to tolerate the maintenance dose of 2.4 mg once weekly, may temporarily decrease 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 the second attempt 
    • In patients with type 2 diabetes, monitor blood glucose before initiating and during treatment
    • Once weekly SC dose escalation schedule
      • 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:1.7 mg or 2.4 mg (maintenance)
• MASH maintenance dose
• Adult dosage
  • 2.4 mg SC weekly
  • If unable to tolerate 2.4 mg/week, may decrease to 1.7 mg weekly; consider reescalation to 2.4 mg once weekly

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”.

Common side effects of Semaglutide include:

• nausea
• vomiting 
• abdominal pain 
• loss of appetite 
• diarrhea
• constipation
• headache
• fatigue
• dyspepsia
• dizziness 
• abdominal distension
• eructation (belching)
• flatulence
• gastroenteritis
• gastroesophageal reflux disease (GERD)
• hypoglycemia (in people with type 2 diabetes) 
• nasopharyngitis

Serious side effects of Semaglutide include:

• increased risk of thyroid tumors (including medullary thyroid carcinoma)
• acute pancreatitis
• changes in vision (including diabetic retinopathy complications)
• acute gallbladder disease
• increased risk of hypoglycemia
• symptoms of serious allergic reactions may include swelling of the face, lips, tongue, or throat, severe rash or itching, very rapid heartbeat, problems breathing or swallowing, fainting, or feeling dizzy 
• acute kidney injury
• severe gastrointestinal problems such as nausea, vomiting, diarrhea, abdominal pain
• increased heart rate
• depression or suicidal thoughts
• risk of pulmonary aspiration during general anesthesia or deep sedation

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 doctor has directed you to use this medication, 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.

• Drug interactions overview
  • Coadministration with insulin secretagogues (e.g., sulfonylureas) or insulin may increase the risk of hypoglycemia; consider a lower dose of the secretagogue or insulin to reduce the risk of hypoglycemia in this setting; inform patients using concomitant medications of the 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

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 the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
• 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
• Postmarketing 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 (e.g., 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
• Acute gallbladder disease events (e.g., cholelithiasis, cholecystitis) reported in GLP-1 receptor agonist trials and postmarketing surveillance; if suspected, gallbladder studies and appropriate clinical follow-up are indicated
• Therapy has been associated with gastrointestinal adverse reactions, sometimes severe; in clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving this drug than placebo; severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists; therapy is not recommended in patients with severe gastroparesis
• Severe GI adverse effects reported; not recommended in patients with severe gastroparesis

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; it 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 the potential benefit justifies the potential risk to the fetus
• Wegovy: May cause fetal harm; advise patients to inform healthcare provider of known or suspected pregnancy; advise patients exposed to this drug during pregnancy to contact Novo Nordisk at 1-877- 390-2760 or www.wegovypregnancyregistry.com
• Clinical Considerations
  • Ozempic, Rybelsus
    • Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes; 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 are already overweight or obese, because of the obligatory weight gain that occurs in maternal tissues during pregnancy
    • Lactation
    • There are no data on the presence of semaglutide in human milk, its effects on the breastfed infant, or milk production. 
    • In lactating rats, semaglutide was detected in milk at levels 3-to 12-fold lower than in maternal plasma