Semaglutide (Monograph)

Brand names: Ozempic, Rybelsus, Wegovy
Drug class: Incretin Mimetics

Medically reviewed by Drugs.com on Feb 10, 2024. Written by ASHP.

Introduction

Antidiabetic agent; glucagon-like peptide-1 (GLP-1) agonist (incretin mimetic).

Uses for Semaglutide

Type 2 Diabetes Mellitus

Glycemic Control

Used as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.

Various preparations of semaglutide are available; Rybelsus oral tablets and Ozempic sub-Q injection are specifically FDA-labeled for use in the management of diabetes mellitus.

Used alone or in combination with one or more antidiabetic agents (e.g., metformin, a sulfonylurea, a thiazolidinedione, a dipeptidyl peptidase [DPP]-4 inhibitor, a sodium-glucose cotransporter 2 [SGLT2] inhibitor, basal insulin) as an adjunct to diet and exercise for the management of type 2 diabetes mellitus.

As add-on therapy, generally has improved glycemic control and reduced body weight compared with add-on therapy with sitagliptin, empagliflozin, extended-release exenatide, liraglutide, dulaglutide, or insulin glargine.

Guidelines for the treatment of type 2 diabetes mellitus generally recommend metformin as first-line therapy in addition to lifestyle modifications in patients with recent-onset type 2 diabetes mellitus or mild hyperglycemia because of its well-established safety and efficacy (i.e., beneficial effects on glycosylated hemoglobin [hemoglobin A_1c; HbA_1c], weight, and cardiovascular mortality).

In patients with metformin contraindications or intolerance (e.g., risk of lactic acidosis, GI intolerance) or in selected other patients, some experts suggest that initial therapy with a drug from another class of antidiabetic agents (e.g., a GLP-1 receptor agonist, sodium-glucose cotransporter 2 [SGLT2] inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, thiazolidinedione, basal insulin) may be acceptable based on patient factors.

May need to initiate therapy with 2 agents (e.g., metformin plus another drug) in patients with high initial HbA_1c (>7.5% or ≥1.5% above target). In such patients with metformin intolerance, some experts suggest initiation of therapy with 2 drugs from other antidiabetic drug classes with complementary mechanisms of action.

Consider early initiation of combination therapy for the treatment of type 2 diabetes mellitus to extend the time to treatment failure and more rapidly attain glycemic goals.

For patients with inadequate glycemic control on metformin monotherapy, consider patient comorbidities (e.g., atherosclerotic cardiovascular disease [ASCVD], established kidney disease, heart failure), hypoglycemia risk, impact on weight, cost, risk of adverse effects, and patient preferences when selecting additional antidiabetic agents for combination therapy.

Consider early introduction of insulin for severe hyperglycemia (e.g., blood glucose of ≥300 mg/dL or HbA_1c >9–10%), especially if accompanied by catabolic manifestations (e.g., weight loss, hypertriglyceridemia, ketosis) or symptoms of hyperglycemia.

Experts recommend that patients with type 2 diabetes mellitus who have established (or are at a high risk for) ASCVD, established kidney disease, or heart failure receive a GLP-1 receptor agonist or SGLT2 inhibitor with demonstrated cardiovascular disease benefit. In patients with these comorbidities, consider GLP-1 receptor agonist or SGLT2 inhibitor therapy independently of patient's HbA_1c.

In patients with type 2 diabetes mellitus and chronic kidney disease (CKD), consider a GLP-1 receptor agonist or SGLT2 inhibitor shown to reduce the risk of CKD progression, cardiovascular events, or both, in addition to metformin therapy or in those in whom metformin cannot be used.

In patients on metformin monotherapy without established ASCVD or indicators of high ASCVD risk, heart failure, or CKD, decision regarding addition of other antidiabetic agents should be based on adverse effects, cost, and individual patient factors.

Not indicated for type 1 diabetes mellitus.

Not studied in patients wtih a history of pancreatitis.

Reduction in Risk of Cardiovascular Events

Semaglutide sub-Q injection (e.g., Ozempic) is used to reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes mellitus and established cardiovascular disease. Semaglutide was noninferior or superior to placebo with regard to primary outcome (first occurrence of cardiovascular death, nonfatal MI, nonfatal stroke) in clinical trials.

Oral^{† [off-label]} semaglutide also evaluated in a cardiovascular outcomes trial in patients with type 2 diabetes mellitus amd demonstrated noninferiority to placebo in time to first MACE. Some data suggest that cardiovascular benefits of semaglutide may be independent of route of administration.

Beneficial Effects on Renal Function

Reduced risk of new or worsening nephropathy^{† [off-label]} observed with use of some GLP-1 receptor agonists (e.g., liraglutide, semaglutide) in patients with type 2 diabetes mellitus at high risk for, or with existing, cardiovascular disease.

Chronic Weight Management

Used as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults who are obese (pretreatment body mass index [BMI] ≥30 kg/m²) and in adults who are overweight (pretreatment BMI ≥27 kg/m²) and who have at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, dyslipidemia).

Used as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in pediatric patients ≥12 years of age with initial BMI at the 95th percentile or greater standardized for age and sex (obesity).

Various preparations of semaglutide are available; Wegovy sub-Q injection is specifically FDA-labeled for use in chronic weight management.

When used in conjunction with a reduced-calorie diet and increased exercise, semaglutide has been shown to substantially decrease body weight in patients with or without diabetes who are obese or overweight.

Do not use in combination with any other semaglutide-containing products or any other GLP-1 receptor agonist. Safety and efficacy of semaglutide in combination with other products used to promote weight loss not established.

Not studied in patients with a history of pancreatitis.

Clinical practice guidelines recommend that patients with excess body weight and associated health risks be treated for obesity. Essential component of therapy is a comprehensive lifestyle intervention; may consider pharmacologic therapy as an adjunct in patients who fail to achieve or sustain clinically meaningful weight loss (generally defined as loss of >4–5% of total body weight) with behavioral modification alone. Evaluate response to drug therapy after 3–4 months; if clinically meaningful weight loss not achieved, consider new treatment plan because patient is likely not responding to the drug.

Related/similar drugs

Repatha, metformin, Ozempic, Mounjaro, Jardiance, simvastatin, Trulicity

Semaglutide Dosage and Administration

General

Pretreatment Screening

• In patients with type 2 diabetes mellitus receiving semaglutide for chronic weight management, monitor blood glucose prior to initiating therapy.

• If used for weight management, select patients for treatment based on baseline BMI.

Patient Monitoring

• Periodically monitor blood glucose and glycosylated hemoglobin (hemoglobin HbA_1c) to determine therapeutic response in patients with type 2 diabetes mellitus.

• In patients with type 2 diabetes mellitus receiving semaglutide for chronic weight management, monitor blood glucose during therapy.

• Monitor patients with a history of diabetic retinopathy for progression of diabetic retinopathy while receiving semaglutide.

• Monitor renal function when initiating semaglutide or escalating dosage in patients reporting severe adverse GI effects. Monitor renal function in patients with renal impairment reporting any adverse effect that could lead to volume depletion.

• Monitor heart rate regularly.

• Monitor for the emergence or worsening of depression, suicidal thoughts or behavior (suicidality), and/or any unusual changes in mood or behavior.

Administration

Oral Administration

Rybelsus

Instruct patients to take tablets at least 30 minutes before the first food, beverage, or other oral drugs of the day; take dose with no more than 120 mL of plain water only.

Taking dose with or <30 minutes before food, beverages (other than plain water), or other oral drugs will lessen semaglutide's effects. Waiting more than 30 minutes to eat after taking the dose may increase drug absorption.

Swallow tablets whole; do not cut, crush, or chew.

If an oral dose is missed, omit the missed dose and take the next dose the following day.

Sub-Q Administration

Ozempic

Administer by sub-Q injection into abdomen, thigh, or upper arm using a prefilled, single patient-use injection pen.

Administer once weekly at any time of day without regard to meals.

If a sub-Q dose is missed, take the dose as soon as possible within 5 days after the missed dose. If >5 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients may resume their regular once-weekly dosing schedule. (See Dosage under Dosage and Administration.)

Administer semaglutide and insulin as separate injections in patients receiving both drugs for diabetes mellitus; do not mix insulin and semaglutide. May inject semaglutide and insulin in the same body region; however, do not administer injections adjacent to each other.

Wegovy

Administer by sub-Q injection into abdomen, thigh, or upper arm using a prefilled, single-use, disposable injection pen.

If a dose is missed and the next scheduled dose is more than 2 days (48 hours) away, administer the missed dose as soon as possible; if the next scheduled dose is less than 2 days (48 hours) away, do not administer the missed dose. Resume dosing on the regularly scheduled day of the week. If 2 or more consecutive doses are missed, resume dosing as scheduled or, if needed, reinitiate therapy and follow the dose escalation schedule.

Administer injections once weekly, on the same day each week, at any time of day without regard to meals.

Dosage

Pediatric Patients

Chronic Weight Management

Sub-Q

Select pediatric patients for treatment based on BMI values provided in the manufacturer's labeling.

Pediatric patients ≥12 years of age: Initially, 0.25 mg once weekly by sub-Q injection; escalate dosage according to the schedule in Table 2 to minimize adverse GI effects.

The recommended maintenance dosage is 2.4 mg once weekly.

If patients do not tolerate the maintenance 2.4 mg once weekly dosage, may reduce dosage to 1.7 mg once weekly. Discontinue therapy if the patient cannot tolerate the 1.7 mg dose.

Adults

Type 2 Diabetes Mellitus

Glycemic Control

Oral

Initially, 3 mg once daily for 30 days. The 3-mg daily dosage is not effective for glycemic control; intended only as a starting dose to reduce GI intolerance.

After 30 days, increase dosage to 7 mg once daily.

After an additional 30 days or more, if needed, increase dosage to 14 mg once daily.

Manufacturer states that taking two 7-mg tablets to achieve a 14-mg dose not recommended.

Switching from oral to sub-Q dosing: Patients taking 14 mg orally once daily may switch to 0.5 mg sub-Q once weekly; start sub-Q dosage the day after the last oral dose.

Glycemic Control and Reduction in Risk of Cardiovascular Events

Sub-Q

Initially, 0.25 mg once weekly for 4 weeks. The 0.25 mg once-weekly dosage is not effective for glycemic control; intended only as a starting dose to reduce GI intolerance.

After 4 weeks, increase dosage to 0.5 mg once weekly. After an additional 4 weeks or more, if needed, may increase dosage to 1 mg once weekly.

Switching from sub-Q to oral dosing: Patients taking 0.5 mg sub-Q once weekly may switch to 7 or 14 mg orally once daily. May begin oral dosing up to 7 days after last sub-Q dose. No equivalent oral dose for 1-mg sub-Q dose.

Chronic Weight Management

Sub-Q

Initially, 0.25 mg once weekly by sub-Q injection; escalate dosage according to the schedule in Table 1 to minimize adverse GI effects.

Recommended maintenance dosage is 2.4 mg once weekly.

If patient does not tolerate dose escalation, consider delaying for 4 weeks.

If patient does not tolerate the recommended maintenance dosage of 2.4 mg once weekly, temporarily decrease dosage to 1.7 mg once weekly for a maximum of 4 weeks, and then increase dosage back to 2.4 mg once weekly. Discontinue therapy if the patient is unable to tolerate the 2.4-mg dose.

Special Populations

Hepatic Impairment

No dosage adjustment is recommended.

Renal Impairment

No dosage adjustment is recommended.

Geriatric Patients

Manufacturer makes no specific recommendations.

Cautions for Semaglutide

Contraindications

• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).

• Prior serious hypersensitivity reaction to semaglutide or any ingredient in the formulation.

Warnings/Precautions

Warnings

Risk of Thyroid C-Cell Tumors

In rodents, semaglutide (at clinically relevant exposures) causes thyroid C-cell tumors that were dose- and duration-dependent. It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the relevance of the findings in rodents to humans has not been determined. (See Boxed Warning.) Cases of MTC reported in patients receiving liraglutide, another GLP-1 receptor agonist, during postmarketing experience; data insufficient to establish or exclude a causal relationship between MTC and liraglutide use in humans. Unknown whether semaglutide causes thyroid C-cell tumors, including MTC, in humans.

Very elevated serum calcitonin values may suggest MTC; such values generally exceed 50 ng/L in patients with MTC. Uncertain value of routine monitoring of serum calcitonin or thyroid ultrasound examinations; further evaluate patients if serum calcitonin is elevated or thyroid nodules noted on physical examination or neck imaging.

Sensitivity Reactions

Hypersensitivity Reactions

Serious hypersensitivity reactions (anaphylaxis, angioedema) reported. If hypersensitivity reaction occurs, discontinue semaglutide and treat patient according to the standard of care and monitor patient until manifestations resolve. Use with caution in patients with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist.

Other Warnings and Precautions

Risks During General Anesthesia and Deep Sedation

GLP-1 agonists are associated with adverse GI effects such as nausea, vomiting, and delayed gastric emptying.

Delayed gastric emptying from GLP-1 agonists can increase the risk of regurgitation and pulmonary aspiration of gastric contents during general anesthesia and deep sedation.

Given these concerns, the American Society of Anesthesiologists (ASA) Task Force on Preoperative Fasting has issued a consensus-based guidance for management of GLP-1 receptor agonists prior to elective surgery. The task force suggests that for patients on daily GLP-1 agonist dosing (irrespective of indication, dose, or type of surgery), consider holding the drug on the day of procedure/surgery. For patients on weekly dosing (irrespective of indication, dose, or type of surgery), consider holding the GLP-1 agonist a week prior to procedure/surgery. If GLP-1 agonists prescribed for diabetes management are held for longer than the dosing schedule, consider consulting an endocrinologist for bridging the antidiabetic therapy to avoid hyperglycemia. These recommendations are based on limited evidence only (case reports).

For patients requiring urgent or emergent procedures, the task force states to proceed and treat the patient as ‘full stomach’ and manage accordingly.

Pancreatitis

Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, reported during clinical trials and in unpublished findings reviewed by the FDA.

Observe patients carefully for manifestations of pancreatitis after drug initiation and dosage increases. Contact clinician promptly if symptoms of pancreatitis (e.g., persistent severe abdominal pain, sometimes radiating to the back, and which may or may not be accompanied by vomiting). If pancreatitis is suspected, promptly discontinue semaglutide and initiate appropriate management. If pancreatitis is confirmed, do not restart therapy.

Not studied in patients with a history of pancreatitis; if used as an antidiabetic agent, consider other antidiabetic agents in such patients.

Diabetic Retinopathy Complications

Diabetic retinopathy complications reported in patients with type 2 diabetes mellitus receiving oral or sub-Q semaglutide. Rapid improvement in glycemic control has been associated with a temporary worsening of diabetic retinopathy. Data are lacking on the effect of long-term glycemic control with semaglutide on diabetic retinopathy. Monitor patients with a history of diabetic retinopathy for progression of this condition.

Sharing of Injection Pens

Do not share semaglutide (Ozempic) injection pens among patients, even if the needle has been changed; sharing poses risk for transmission of blood-borne pathogens.

Use with Drugs Known to Cause Hypoglycemia

Patients receiving semaglutide in combination with an insulin secretagogue (e.g., a sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Caution and educate patients about risks and about signs and symptoms of hypoglycemia; reduction in sulfonylurea or insulin dosage may be necessary.

Renal Effects

Acute kidney injury and worsening of chronic renal failure (sometimes requiring hemodialysis) reported. Patients with baseline renal impairment may be at greater risk; however, some patients did not have known underlying renal disease.

Other factors (nausea, vomiting, diarrhea, or dehydration) were present in most patients. Because such adverse GI effects may worsen renal function, use caution and monitor renal function when initiating semaglutide or escalating dosage in patients reporting severe adverse GI effects.

Monitor renal function in patients with renal impairment reporting any adverse effect that could lead to volume depletion.

Elevated Heart Rate

Increases in heart rate reported.

Monitor heart rate regularly in patients receiving semaglutide. Advise patients to inform their clinician if palpitations or feelings of a racing heartbeat occur while at rest during semaglutide therapy; if a sustained increase in resting heart rate occurs, discontinue therapy.

Suicidality

Suicidal behavior and ideation reported with other weight management products.

Monitor patients for the emergence or worsening of depression, suicidal thoughts or behavior (suicidality), and/or any unusual changes in mood or behavior.

If a patient experiences suicidal thoughts or behaviors while receiving semaglutide, discontinue the drug. Avoid semaglutide in patients with a history of suicidal attempts or active suicidal ideation.

Acute Gallbladder Disease

Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in clinical trials with GLP-1 receptor agonists and during postmarketing experience. In placebo-controlled trials, cholelithiasis was reported in 1% of patients treated with semaglutide 7 mg (administered as the oral tablets for the treatment of type 2 diabetes mellitus). Cholelithiasis was not reported in semaglutide 14 mg or placebo-treated patients. In patients receiving semaglutide injection for weight loss management, incidence of cholelithiasis and cholecystitis was higher in pediatric patients receiving the drug than in adults.

If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.

Immunogenicity

Potential risk of immunogenicity. The presence of these antibodies has the potential to increase the risk of local skin reactions, hypersensitivity, or anaphylactic reactions and may also neutralize the therapeutic effects of GLP-1 receptor agonists; however, clinical importance appears to be low in most patients. The in vitro neutralizing activity of the antibodies is unknown.

Specific Populations

Pregnancy

Data are lacking on the use of semaglutide in pregnant women. Reproduction studies in animals have shown teratogenic effects (e.g., mortality, structural abnormalities, growth alterations, early pregnancy loss).

Poorly controlled diabetes mellitus during pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortion, preterm delivery, and delivery complications and also increases risk of major fetal birth defects, stillbirth, and macrosomia-related morbidity.

Manufacturer of the semaglutide preparations used for diabetic management states to use semaglutide during pregnancy only if the potential benefit justifies the potential risk to the fetus. Manufacturer of the semaglutide preparation used for weight control management states that weight loss offers no benefit to a pregnant patient and may cause fetal harm; if a patient becomes pregnant while receiving the drug, discontinue treatment.

A pregnancy exposure registry has been established to monitor pregnancy outcomes in women exposed to Wegovy; encourage pregnant women exposed to the drug to contact 1-800-727-6500.

Females and Males of Reproductive Potential

Discontinue semaglutide at least 2 months before a pregnancy is planned to account for the long half-life of the drug.

Lactation

Semaglutide is distributed into milk in rats; not known whether distributed into milk in humans.

Consider benefits of breast-feeding and importance of semaglutide to the woman along with any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Manufacturer states that breast-feeding is not recommended during treatment with oral semaglutide. Salcaprozate sodium (SNAC), an absorption enhancer in the oral formulation has been detected in milk of lactating rats at levels 2–12 times higher than in maternal plasma following a single maternal administration.

Pediatric Use

Safety and efficacy of semaglutide for type 2 diabetes mellitus (Ozempic, Rybelsus) not established in children or adolescents <18 years of age.

Safety and efficacy of semaglutide (Wegovy) for chronic weight management established in pediatric patients ≥12 years of age with BMI corresponding to ≥95th percentile standardized for age and sex. Insufficient data in pediatric patients with type 2 diabetes treated with Wegovy for obesity to determine if there is an increased risk of hypoglycemia with the drug similar to that reported in adults. Inform patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

When initiating Wegovy in pediatric patients ≥12 years of age with type 2 diabetes, consider reducing dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Hepatic Impairment

No substantial differences in the pharmacokinetics of semaglutide administered orally or sub-Q have been observed in patients with mild, moderate, or severe hepatic impairment.

Exposure of SNAC, an absorption enhancer in the oral formulation, increased with increasing hepatic impairment; not considered clinically relevant. Data lacking on the long-term safety of SNAC in patients with hepatic impairment.

Renal Impairment

No substantial differences in the pharmacokinetics of semaglutide administered orally or sub-Q have been observed in patients with mild, moderate, or severe renal impairment, including patients with ESRD.

Exposure of SNAC, an absorption enhancer in the oral formulation, increased with increasing renal impairment; not considered clinically relevant. Data lacking on the long-term safety of SNAC in patients with renal impairment. No effects of hemodialysis on pharmacokinetics of orally administered semaglutide or SNAC.

Disease of the Upper GI Tract

No clinically important pharmacokinetic differences between patients with type 2 diabetes mellitus with or without upper GI disease (chronic gastritis and/or gastroesophageal reflux disease) who received oral semaglutide once daily for 10 consecutive days.

Common Adverse Effects

Oral administration (≥5%): Nausea, abdominal pain/discomfort, diarrhea, decreased appetite, vomiting, constipation.

Sub-Q administration with Ozempic (≥5%): Nausea, vomiting, diarrhea, abdominal pain, constipation.

Sub-Q administration with Wegovy (≥5%): nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease, nasopharyngitis.

Drug Interactions

Low potential to inhibit or induce CYP enzymes or to inhibit drug transporters.

Orally Administered Drugs

Possible decreased rate and extent of absorption of concomitantly administered oral drugs; use caution with concomitantly administered oral drugs. In clinical pharmacology trials, sub-Q semaglutide did not affect the absorption of orally administered drugs (e.g., atorvastatin, digoxin, metformin, ethinyl estradiol, levonorgestrel, warfarin) to any clinically important extent.

No clinically important effects of oral semaglutide on absorption of other drugs (e.g., digoxin, ethinyl estradiol, levonorgestrel, furosemide, levothyroxine, lisinopril, metformin, omeprazole, rosuvastatin, warfarin) in drug interaction studies. Advise patients receiving oral semaglutide concomitantly with other oral drugs to closely follow oral semaglutide administration instructions. Consider increased clinical or laboratory monitoring in patients receiving concomitant therapy with drugs that have a narrow therapeutic index or that require clinical monitoring.

Specific Drugs

Semaglutide Pharmacokinetics

Absorption

Bioavailability

Sub-Q administration: 89–94% (absolute); exposure similar with administration in abdomen, thigh, or upper arm.

Oral administration (coformulated with salcaprozate sodium [SNAC] to facilitate absorption): 0.4–1% (absolute).

Peak plasma concentration achieved in 1 hour (oral administration) or 1–3 days (sub-Q administration). Steady state achieved after 4–5 weeks with oral or sub-Q dosing.

Distribution

Plasma Protein Binding

>99%.

Elimination

Metabolism

Mainly proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid sidechain.

Elimination Route

Mainly excreted in urine and feces. Approximately 3% of a dose is excreted in urine as unchanged drug.

Half-life

Elimination half-life is approximately 1 week.

Stability

Storage

Oral

20–25°C in original container; may expose to 15–30°C. Protect from moisture.

Parenteral

Injection

Ozempic: Before first use, store in refrigerator (2–8°C); do not freeze. After first use, can be stored at room temperature (15–30ºC) or refrigerated (2–8°C). Do not freeze and do not use if frozen; protect from excessive heat and light. When refrigerated, do not place injection pens directly next to the cooling element. Discard injection pen 56 days after first use.

Wegovy: Refrigerate between 2–8°C; do not freeze and protect from light. If needed, the pen can be stored at 8–30°C for up to 28 days prior to cap removal,. Store in the original carton until time of administration. Discard single-use prefilled pens after use.

Actions

• Long-acting GLP-1 receptor agonist; 94% amino acid sequence homology to endogenous human GLP-1.

• Stimulates insulin release in the presence of elevated glucose concentrations, suppresses glucose-dependent glucagon release, and slows gastric emptying, resulting in lower fasting and postprandial blood glucose concentrations and weight loss in patients with type 2 diabetes mellitus.

• Long-acting GLP-1 receptor agonists (e.g., albiglutide [no longer commercially available in the US], dulaglutide, exenatide extended-release, liraglutide, semaglutide) induce marked reductions in fasting plasma glucose (by stimulating insulin secretion) and modest reductions in postprandial glucose, while short-acting GLP-1 receptor agonists (e.g., exenatide, lixisenatide), have less of an effect on fasting plasma glucose concentrations and more of an effect on reducing postprandial glucose concentrations (by slowing gastric emptying and inhibiting glucagon secretion).

• Does not appear to be associated with clinically important prolongation of the corrected QT interval (QT_c).

Advice to Patients

• Importance of patients reading the medication guide and instructions for use prior to initiating therapy and each time prescription is refilled.

• Importance of informing patients that semaglutide causes thyroid C-cell tumors in rats and that the relevance of this finding in humans is unknown. Importance of advising patients receiving semaglutide to report symptoms such as a lump in the neck, hoarseness, dysphagia, or dyspnea, which may be suggestive of thyroid cancer.

• Importance of informing patients of the possibility of pancreatitis with semaglutide therapy. Importance of informing patients about signs and symptoms of pancreatitis, including persistent severe abdominal pain sometimes radiating to the back that may or may not be accompanied by vomiting; importance of patient discontinuing semaglutide and promptly notifying clinician if such signs or symptoms occur.

• Importance of informing patients to contact a clinician if changes in vision are experienced during treatment with semaglutide.

• Importance of informing patients that they should never share injection pens containing semaglutide with another person, even if the needle is changed; sharing of the pen may pose a risk of transmitting or acquiring infection.

• Importance of informing patients of the potential risk of dehydration due to adverse GI effects; importance of advising patients to drink fluids to avoid dehydration. Importance of informing patients of the potential risk for worsening renal function, which in some cases may require dialysis.

• Importance of informing patients of possibility of serious allergic or hypersensitivity reactions (e.g., anaphylaxis). Patients should be instructed to discontinue semaglutide and promptly seek medical advice if symptoms of a serious hypersensitivity reaction (e.g., swelling of the face, lips, tongue, or throat; difficulty breathing or swallowing; severe rash or itching; fainting or feeling dizzy; very rapid heart rate) occur.

• Importance of providing information regarding the potential risks and advantages of semaglutide therapy and of alternative modes of treatment.

• If the drug is being used as an antidiabetic agent, instruct the patient regarding diabetes self-management practices, such as regular physical activity, adhering to meal planning, periodic blood glucose monitoring, HbA_1c testing, recognition and management of hypoglycemia and hyperglycemia, and assessment of other diabetic complications. Advise patients to seek medical advice promptly during periods of stress (e.g., fever, trauma, infection, surgery) as medication requirements may change.

• Importance of advising patients that the most common adverse effects of oral semaglutide are nausea, abdominal pain, diarrhea, decreased appetite, vomiting, and constipation and that the most common adverse effects of sub-Q semaglutide therapy are nausea, vomiting, diarrhea, abdominal pain, and constipation. Advise patients that nausea, vomiting, and diarrhea are most common when first initiating oral or sub-Q semaglutide therapy but these effects decrease over time in most patients.

• Instruct patients to inform their healthcare providers of palpitations or feelings of a racing heartbeat while at rest during semaglutide treatment.

• Advise patients to report emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Inform patients that if they experience suicidal thoughts or behaviors, they should stop taking the drug.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Breast-feeding is not recommended during treatment with oral semaglutide due to the unknown potential for serious adverse effects from accumulation of salcaprozate sodium (SNAC), an absorption enhancer in the oral formulation, in milk; alternative formulations of semaglutide (i.e., injection) are available for use during lactation. Advise patients who are exposed to the Wegovy preparation during pregnancy to contact the manufacturer at 1-800-727-6500.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• Tirzepatide vs semaglutide: How do they compare?
• How does semaglutide work for weight loss?
• Why am I not losing weight on Ozempic?
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• What foods should I eat or avoid when taking Rybelsus?
• Does taking Ozempic affect your face?
• Why does Ozempic cause a dry mouth or taste changes?
• How much does semaglutide cost?
• Does Wegovy make you pee a lot or urine smell?

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