semaglutide

REMS

Ozempic and RybelsusType 2 diabetes mellitus (as adjunct to diet and exercise).
OzempicTo reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes mellitus and established cardiovascular disease.
OzempicTo reduce the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in patients with type 2 diabetes mellitus and chronic kidney disease.
WegovyChronic weight management in:
- Adults who are obese (body mass index [BMI] ≥30 kg/m²) OR are overweight (BMI ≥27 kg/m²) with ≥1 weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes) (as adjunct to reduced-calorie diet and ↑ physical activity).
- Pediatric patients ≥12 yr old who are obese (initial BMI ≥95th percentile standardized for age and sex) (as adjunct to reduced-calorie diet and ↑ physical activity).
WegovyTo reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal MI, or nonfatal stroke) in adults with established cardiovascular disease and who are either obese or overweight.

Action ⬆ ⬇

Acts as an acylated human glucagon-like peptide-1 (GLP-1, an incretin) receptor agonist; increases intracellular cyclic AMP (cAMP), leading to insulin release when glucose is elevated, which then subsides as blood glucose decreases toward euglycemia. Also decreases glucagon secretion and delays gastric emptying. Also helps to suppress appetite, leading to decreased caloric intake.

Therapeutic effects:

Improved glycemic control.
Reduction in risk of cardiovascular death, nonfatal MI, or nonfatal stroke patients with type 2 diabetes mellitus and established cardiovascular disease.
Reduction in risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in patients with type 2 diabetes mellitus and chronic kidney disease.
Reduction in body weight.

Pharmacokinetics ⬆ ⬇

Absorption: 89% absorbed following SUBQ injection; 0.4–1% absorbed following oral administration.

Distribution: Minimally distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Endogenously metabolized; eliminated in the urine (3% as unchanged drug) and feces.

Half-Life: 1 wk.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
SUBQ	unknown	1–3 days	unknown
PO	unknown	1 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Personal or family history of medullary thyroid carcinoma
;
Multiple endocrine neoplasia syndrome type 2
;
Type 1 diabetes;
Diabetic ketoacidosis;
Severe GI disease (including severe gastroparesis);
Lactation: Avoid use of Rybelsus while breastfeeding.

Use Cautiously in:

History of pancreatitis;
Diabetic retinopathy (↑ risk of complications);
History of angioedema or anaphylaxis to another GLP-1 receptor agonist;
History of suicidal attempt or active suicidal ideations;
Undergoing elective surgery or procedure requiring general anesthesia or deep sedation;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk; insulin recommended for glucose management in pregnancy;
Lactation: Use injectable formulations while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children <12 yr (Wegovy) or <18 yr (Ozempic or Rybelsus).

Adv. Reactions/Side Effects ⬆ ⬇

CV: ↑heart rate

Derm: hair loss

EENT: retinopathy complications

Endo: hypoglycemia, MEDULLARY THYROID CARCINOMA

GI: abdominal pain, constipation, diarrhea, nausea, vomiting, ↓appetite, ↑amylase, ↑lipase, abdominal distention, cholecystitis, cholelithiasis, dyspepsia, flatulence, PANCREATITIS, vomiting

GU: acute kidney injury

Local: injection site reactions

Neuro: fatigue, headache, dizziness, SUICIDAL BEHAVIOR/IDEATION (WEGOVY ONLY)

Resp: aspiration

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with agents that increase insulin secretion, including sulfonylureas or insulin, may ↑ risk of serious hypoglycemia; use cautiously and consider dose ↓ of agent increasing insulin secretion.
May alter absorption of concurrently administered oral medications due to delayed gastric emptying.

Route/Dosage ⬆ ⬇

Type 2 Diabetes

Rybelsus formulations should not be substituted on a mg-per-mg basis. Only one formulation should be used at one time.
PO (Adults ): Rybelsus (formulation R1): 3 mg once daily for 30 days, then 7 mg once daily; after 30 days, may ↑ to 14 mg once daily if additional glycemic control needed. Rybelsus (formulation R2): 1.5 mg once daily for 30 days, then 4 mg once daily; after 30 days, may ↑ to 9 mg once daily if additional glycemic control needed.
SC (Adults ): Ozempic: 0.25 mg once weekly initially for 4 wk, then 0.5 mg once weekly for 1 wk; may then ↑ dose after ≥4 wk, if additional glycemic control needed, to 1 mg once weekly; may then ↑ dose after ≥4 wk, if additional glycemic control needed, to 2 mg once weekly.

Reduction in Risk of Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease

SC (Adults ): Ozempic: 0.25 mg once weekly initially for 4 wk, then 0.5 mg once weekly for 1 wk; may then ↑ dose after ≥4 wk, if additional glycemic control needed, to 1 mg once weekly; may then ↑ dose after ≥4 wk, if additional glycemic control needed, to 2 mg once weekly.

Reduction in Risk of Sustained eGFR Decline, End-Stage Kidney Disease, and Cardiovascular Death in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease

SC (Adults ): Ozempic: 0.25 mg once weekly initially for 4 wk, then 0.5 mg once weekly for 1 wk; then ↑ dose after ≥4 wk to 1 mg once weekly.

Chronic Weight Management

SC (Adults and Children ≥12 yr): Wegovy: 0.25 mg once weekly initially for 4 wk, then 0.5 mg once weekly for 4 wk, then 1 mg once weekly for 4 wk, then 1.7 mg once weekly for 4 wk, then 1.7 mg or 2.4 mg once weekly thereafter.

Reduction in Risk of Major Adverse Cardiovascular Events in Patients With Established Cardiovascular Disease Who Are Overweight or Obese

SC (Adults ): Wegovy: 0.25 mg once weekly initially for 4 wk, then 0.5 mg once weekly for 4 wk, then 1 mg once weekly for 4 wk, then 1.7 mg once weekly for 4 wk, then 1.7 mg or 2.4 mg once weekly thereafter.

Availability ⬆ ⬇

Tablets (Rybelsus [formulation R1]): 3 mg; 7 mg; 14 mg
Tablets (Rybelsus [formulation R2]): 1.5 mg; 4 mg; 14 mg
Solution for injection (Ozempic) (prefilled pens): 2 mg/3 mL (delivers doses of 0.25 mg or 0.5 mg); 4 mg/3 mL (delivers dose of 1 mg); 8 mg/3 mL (delivers dose of 2 mg)
Solution for injection (Wegovy) (prefilled pens): 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

Assessment ⬆ ⬇

Observe patient taking concurrent insulin or medication that ↑ insulin secretion for signs/symptoms of hypoglycemia.
Monitor for pancreatitis. If pancreatitis suspected, discontinue semaglutide. If pancreatitis confirmed, do not restart semaglutide.
Monitor weight before and periodically during therapy.
Monitor for signs/symptoms of hypersensitivity reactions (swelling of face, lips, tongue, or throat; problems breathing or swallowing; severe rash or itching; fainting or feeling dizzy; very rapid heartbeat) during therapy.
Monitor HR regularly during therapy. If sudden sustained ↑ in resting HR occurs, discontinue semaglutide.

Lab Test Considerations:

Monitor A1c periodically during therapy to evaluate effectiveness.
- Wegovy: In patients with type 2 diabetes, monitor blood glucose prior to starting and during therapy.
- May ↑ lipase and amylase.
- Monitor renal function when initiating or escalating doses of semaglutide.

Implementation ⬆ ⬇

Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin.
Switching between Rybelsus formulations: Do not switch between Rybelsus formulations during the initiation phase (Days 1–30); may switch between Rybelsus formulations after 30 days of treatment. When switching between formulations, initiate the other Rybelsus formulation the day after discontinuing the previous Rybelsus formulation. Patients treated with Rybelsus (formulation R1) 7 mg once daily can be switched to Rybelsus (formulation R2) 4 mg once daily. Patients treated with Rybelsus (formulation R1) 14 mg once daily can be switched to Rybelsus (formulation R2) 9 mg once daily.
Switching from Ozempic to Rybelsus (formulation R1): One week after discontinuing Ozempic 0.5 mg SUBQ once weekly, start Rybelsus (formulation R1)7 mg or 14 mg PO once daily.
Switching from Ozempic to Rybelsus (formulation R2): One week after discontinuing Ozempic 0.5 mg SUBQ once weekly, start Rybelsus (formulation R2)4 mg or 9 mg PO once daily.
PO: Administer ≥30 min before 1st food, beverage, or other oral medications of the day with no more than 4 oz of plain water only. Waiting <30 min or taking Rybelsus with food, beverages (other than plain water), or other PO medications ↓ absorption and will lessen effects. Waiting >30 min to eat may ↑ absorption. DNC: Swallow tablets whole; do not split, crush, or chew.
SC: Administer once weekly on same day each wk, any time of day without regard to meals. May change day of injection as long as time between doses is >48 hr. Inject into abdomen, thigh, or upper arm, rotating sites each wk. Solution is clear and colorless; do not administer solutions that are cloudy, discolored, or contain particulate matter. Store pens in refrigerator in original box until administration to protect from light; do not freeze. Wegovy: Single-use pens are stable for up to 28 days. Ozempic multidose pens are stable if refrigerated without the needle for 56 days after 1st use. Use a new needle for each injection.
- Wegovy: If dose escalation is not tolerated, may delay dose escalation for 4 wk. If patients do not tolerate maintenance dose of 2.4 mg once weekly, dose can be temporarily ↓ to 1.7 mg once weekly, for a maximum of 4 wk. After 4 wk, ↑ to maintenance dose of 2.4 mg once weekly. Discontinue Wegovy if patient cannot tolerate 2.4-mg dose.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take semaglutide as directed. If a PO dose is missed, omit dose and take next dose the following day. Instruct patient in correct technique for injection and disposal of materials. Follow manufacturer's instructions for pen use. Pen should never be shared between patients, even if needle is changed. Administer missed Ozempic doses as soon as remembered within 5 days of missed dose; if >5 days, skip dose and administer next dose on regular scheduled day. Administer missed Wegovy doses as soon as remembered. If one dose is missed and next scheduled dose is >2 days away (48 hr), administer Wegovy as soon as possible. If one dose is missed and the next scheduled dose is <2 days away (48 hr), omit dose and resume dosing on regularly scheduled day of wk. If >2 consecutive doses are missed, resume dosing as scheduled or restart Wegovy and follow dose escalation schedule; may ↓ occurrence of GI symptoms. Advise patient to read the Medication Guide before starting therapy and with each Rx refill in case of changes.
Advise patient taking insulin to never mix insulin and semaglutide together. Give as two separate injections. Both injections may be given in the same body area but should not be given right next to each other.
Explain to patient that this medication controls hyperglycemia but does not cure diabetes. Therapy is long term.
Review signs/symptoms of hypoglycemia (sweating, hunger, dizziness, ↑ HR, irritability, confusion, seizures) and hyperglycemia (thirst, hunger, frequent urination, fatigue, blurred vision) with patient. Advise patient to carry a form of sugar and identification describing disease process and medication regimen at all times. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 teaspoons of sugar, honey, or corn syrup dissolved in water and notify health care provider.
Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hypoglycemic or hyperglycemic episodes.
Instruct patient in proper testing of serum glucose and ketones. These tests should be closely monitored during periods of stress or illness, and health care provider should be notified if significant changes occur.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications.
Advise patient to notify health care provider and discontinue semaglutide immediately if signs/symptoms of pancreatitis (nausea, vomiting, abdominal pain radiating to back), palpitations or ↑ HR while at rest, or hypersensitivity (swelling of face, lips, tongue, or throat; problems breathing or swallowing; severe rash or itching; fainting or feeling dizzy; very rapid heartbeat) occur.
Inform patient of risk of benign and malignant thyroid C-cell tumors. Advise patient to notify health care provider if symptoms of thyroid tumors (lump in neck, hoarseness, trouble swallowing, shortness of breath) occur.
Advise patient to inform health care provider of medication regimen before procedures or surgery due to ↑ risk of aspiration with general or deep sedation.
Instruct patient with history of diabetic retinopathy to have ophthalmic monitoring for progression of disease throughout therapy.
Rep: Insulin is the preferred method of controlling blood glucose during pregnancy. Advise women of reproductive potential and men with female partners of reproductive potential to discontinue semaglutide in women ≥2 mo before a planned pregnancy to allow for long washout period of semaglutide. Counsel women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Encourage pregnant patients to enroll in registry that monitors outcomes in women exposed to semaglutide during pregnancy by calling 1-877-390-2760 or visiting www.wegovypregnancyregistry.com.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇