semaglutide (Rx)

Brand and Other Names:Ozempic, Rybelsus
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Dosing & Uses


Dosage Forms & Strengths

SC solution single-patient-use pen (Ozempic)

  • 1.34mg/mL; delivers doses of 0.25mg, 0.5mg, or 1mg

oral tablet (Rybelsus)

  • 3mg
  • 7mg
  • 14mg

Type 2 Diabetes Mellitus

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus


  • 0.25 mg SC qWeek for 4 weeks initially; THEN increase the dosage to 0.5 mg qWeek
  • If glycemic control not achieved after at least 4 weeks on 0.5-mg dose, can increase to 1 mg qWeek


  • Initial: 3 mg PO qDay x30 days; the 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 PO qDay
  • After 30 days on 7 mg/day: May increase dose to 14 mg PO qDay if additional glycemic control needed
  • NOTE: Taking two 7-mg tablets to achieve 14 mg dose is not recommended

Switching between Ozempic (SC) and Rybelsus (PO)

  • Taking 14 mg/day PO: Transition to 0.5 mg SC qWeek on day after last PO dose
  • Taking 0.5 mg/week SC: Transition to 7mg or 14 mg PO starting up to 7 days after last SC injection
  • There is no equivalent PO dose for the 1-mg SC dose

Dosage Modifications

Renal or hepatic impairment

  • No dosage adjustment required

Upper GI tract disease

  • PO: No dosage adjustment required

Dosing Considerations

Limitations of use

  • Not recommended as a first-line therapy for patients who have inadequate glycemic control on diet and exercise because of uncertain relevance of rodent C-cell tumor findings to humans
  • Not studied in patients with a history of pancreatitis; consider other antidiabetic therapies
  • SC administration is not a substitute for insulin
  • Not indicated for type 1 diabetes mellitus or for treatment of diabetic ketoacidosis, as it would not be effective in these settings

<18 years: Safety and efficacy not established



Interaction Checker

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            Adverse Effects

            >10% (SC)

            Nausea (15.8-20.3%)

            Documented symptomatic hypoglycemia, adjunctive therapy [≤70 mg/dL glucose threshold] (16.7-29.8%)

            Severe or symptomatic hypoglycemia, adjunctive therapy [≤56 mg/dL glucose threshold] (8.3-10.7%)

            >10% (PO)

            Nausea (11-20%)

            Abdominal pain (10-11%)

            1-10% (SC)

            Vomiting (5-9.2%)

            Diarrhea (8.5-8.8%)

            Abdominal pain (5.7-7.3%)

            Constipation (3.1-5%)

            Dyspepsia (2.7-3.5%)

            Eructation (1.1-2.7%)

            Documented symptomatic hypoglycemia, monotherapy [≤70 mg/dL glucose threshold] (1.6-3.8%)

            Flatulence (0.4-1.5%)


            1-10% (PO)

            Diarrhea (9-10%)

            Decreased appetite (6-9%)

            Vomiting (6-8%)

            Constipation (5-6%)

            Abdominal distension (2-3%)

            Dyspepsia (0.6-3%)

            GERD (2%)

            Gastritis (2%)

            Eructation (0.6-2%)

            Flatulence (1-2%)

            Cholelithiasis (1%)

            <1% (SC)

            Gastritis (0.4-0.8%)

            Cholelithiasis (0.4%)

            Fatigue (>0.4%)

            Dysgeusia (>0.4%)

            Dizziness (>0.4%)

            Injection site reaction (0.2%)

            Frequency Not Defined (PO)

            Increased amylase and lipase

            Increased HR



            Black Box Warnings

            In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures; unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined

            Contraindicated in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2

            Advise patients of the potential risk for MTC with semaglutide and the possible symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness)

            Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with semaglutide


            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


            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

            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 (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 (see Contraindications)

            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
            • 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 & 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

            Clinical Considerations

            • 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


            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

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.



            Mechanism of Action

            Glucagon-like peptide-1 (GLP-1) agonist

            Incretins, such as GLP-1, enhance glucose-dependent insulin secretion by pancreatic beta-cells, suppress inappropriately elevated glucagon secretion, and slow gastric emptying



            • Bioavailability: 89%
            • Peak plasma time: 1-3 days
            • Plasma concentration, steady-state: 65 ng/mL (0.5 mg/week); 123 ng/mL (1 mg/week)
            • Similar exposure is achieved with SC administration of semaglutide in the abdomen, thigh, or upper arm


            • Absolute bioavailability: 0.4-1%
            • Peak plasma time: 1 hr
            • Plasma concentration, steady-state: 6.7 nmol/L (7 mg/day); 14.6 nmol/L (14 mg/day)
            • Steady-state: 4-5 weeks


            Vd: 12.5 L (SC); 8 L (PO)

            Protein binding: >99% (bound to plasma albumin)


            Primary route: Proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid sidechain


            Half-life: ~1 week

            Clearance: 0.05 L/hr (SC); 0.04 L/hr (PO)

            Excretion: Primary excretion routes are urine and feces; ~3% of absorbed dose is excreted in urine unchanged



            SC Administration

            Administer SC to abdomen, thigh, or upper arm

            Administer once weekly, on the same day each week, at any time of the day, with or without meals

            Day of weekly administration can be changed if necessary as long as the time between 2 doses is at least 2 days (>48 hours)

            Use a different injection site each week when injecting in the same body region

            Visually inspect before use; drug should appear clear and colorless

            Do not use semaglutide if particulate matter and coloration is seen

            When used with insulin, administer as separate injections and never mix the products; it is acceptable to inject semaglutide and insulin in the same body region but injections should not be adjacent to each other

            Missed SC dose

            • If missed dose is ≤5 days: Administer dose as soon as possible
            • If missed dose >5 days: Skip missed dose and administer next dose on the regularly scheduled day; patients can then resume their regular once weekly dosing schedule

            Oral Administration

            Take at least 30 minutes before first food, beverage, or other oral medication of the day with no more than 4 oz of plain water only

            Waiting <30 minutes, or taking with food, beverages (other than plain water), or other oral medications decrease efficacy by decreasing semaglutide absorption

            Waiting to take after 30 minutes to eat may increase semaglutide absorption

            Swallow tablets whole; do not split, crush, or chew

            Missed oral dose

            • If a dose is missed, the missed dose should be skipped, and the next dose should be taken the following day



            • Unused SC pens
              • Refrigerate at 36-46ºF (2-8ºC)
              • Do not store in freezer or directly adjacent to the refrigerator cooling element
              • Do not freeze and do not use if frozen
            • After first SC use
              • Store at room temperature, 59-86°F (15-30°C) or refrigerate at 36-46ºF (2-8ºC) for up to 56 days
              • Do not freeze
              • Keep pen cap on when not in use
              • Protect from excessive heat and sunlight

            Oral tablets

            • Store at 68-77ºF (20-25ºC); excursions permitted to 59-86ºF (15-30ºC)
            • Store and dispense in the original carton
            • Store tablet in the original blister card until use to protect tablets from moisture
            • Store product in a dry place away from moisture




            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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