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 (injection only).
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 increased 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 increased physical activity).

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, non-fatal MI, or non-fatal stroke.
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.

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;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk; insulin recommended for glucose management in pregnancy;
Lactation: Use 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)

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

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

Route/Dosage ⬆ ⬇

Type 2 Diabetes

PO (Adults ): 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.
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 needed, to 1 mg once weekly; may then ↑ dose after ≥4 wk, if 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 needed, up 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 2.4 mg once weekly thereafter.

Availability ⬆ ⬇

Tablets (Rybelsus): 3 mg; 7 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 for signs and symptoms of hypoglycemic reactions (sweating, hunger, weakness, dizziness, tremor, tachycardia, anxiety, headache, blurred vision, slurred speech, irritability).
Monitor for pancreatitis (persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting). If pancreatitis is suspected, discontinue semaglutide; if confirmed, do not restart semaglutide.
Monitor weight before and periodically during therapy.
Monitor for signs and 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 heart rate regularly during therapy. If a sudden sustained increase in resting heart rate occurs, discontinue semaglutide.

Lab Test Considerations:

Monitor serum HbA_1c 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 pancreatic amylase.

Implementation ⬆ ⬇

Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin.
Patients treated with PO Rybelsus 14 mg daily can be transitioned to Ozempic SUBQ 0.5 mg once-weekly. Patients can start Ozempic the day after their last dose of Rybelsus. Patients treated with once weekly Ozempic 0.5 mg SUBQ can be transitioned to PO Rybelsus 7 mg or 14 mg. Patients can start Rybelsus up to 7 days after last injection of Ozempic. There is no equivalent dose of Rybelsus for Ozempic 1 mg.
PO: Administer at least 30 min before first food, beverage, or other oral medications of the day with no >4 oz of plain water only. Waiting <30 min, or taking Rybelsus with food, beverages (other than plain water), or other PO medications decreases absorption and will lessen effects. Waiting >30 min to eat may increase absorption. DNC: Swallow tablets whole; do not split, crush, or chew.
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 decreased to 1.7 mg once-weekly, for a maximum of 4 wk. After 4 wk, increase to maintenance dose of 2.4 mg once-weekly. Discontinue Wegovy: if patient cannot tolerate 2.4 mg dose.
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 multi-dose pens are stable if refrigerated without the needle for 56 days after 1st use. Use a new needle for each injection.

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 1 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 reduce 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 and semaglutide to never mix insulin and semaglutide together. Give as 2 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 of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 tsp of sugar, honey, or corn syrup dissolved in water and notify health care professional.
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 professional should be notified if significant changes occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Advise patient to notify health care professional and discontinue semaglutide immediately if signs of pancreatitis (nausea, vomiting, abdominal pain radiating to back), palpitations 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 professional if symptoms of thyroid tumors (lump in neck, hoarseness, trouble swallowing, shortness of breath) occur.
Advise patient to inform health care professional of medication regimen before treatment or surgery.
Advise patient to carry a form of sugar (sugar packets, candy) and identification describing disease process and medication regimen at all times.
Rep: Insulin is the preferred method of controlling blood glucose during pregnancy. Advise females of reproductive potential and males with female partners of reproductive potential to discontinue semaglutide in women at least 2 mo before a planned pregnancy to allow for long washout period of semaglutide. Counsel female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Inform patient of pregnancy exposure registry that monitors pregnancy outcomes in women exposed to semaglutide during pregnancy. Pregnant women exposed to semaglutide and health care professionals are encouraged to contact Novo Nordisk at 1-877-390-2760 or www.wegovypregnancyregistry.com.
Emphasize the importance of routine follow-up exams.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇