semaglutide

Semaglutide is a medication used in the treatment of type 2 diabetes mellitus and for chronic weight management, along with physical exercise, dietary restrictions, and lifestyle changes.

Semaglutide is used to control blood sugar levels when other commonly prescribed medications do not control the sugar levels adequately in type 2 diabetes, but cannot be used to treat type 1 diabetes or diabetic ketoacidosis, a complication of diabetes.

Semaglutide belongs to a class of medications known as glucagon-like peptide-1 (GLP-1) agonists which work by mimicking GLP-1, a natural human hormone that regulates blood sugar levels. Semaglutide reduces blood sugar levels by increasing the secretion of insulin in the pancreatic beta cells and reducing glucagon secretion. Insulin is a hormone that helps move the sugar from the blood into the cells for use as energy, while glucagon increases blood sugar level and prevents it from dropping too low.

Semaglutide also slows down the passage of food through the gastrointestinal tract (gastric emptying), which reduces post-meal glucagon secretion and increases in sugar levels. Semaglutide can be used in patients who have impaired functioning of insulin and glucagon, but cannot be used as a substitute for insulin. The delayed gastric emptying can keep a person sated for a longer period, which helps with weight management. Semaglutide may also help in regulating appetite and caloric intake by acting on the GLP-1 receptors in the brain.

Semaglutide brands Ozempic injections and Rybelsus oral tablets are used to treat diabetes and the brand Wegovy (injection) is used for weight management in overweight or obese persons with any weight-related additional condition such as diabetes, high blood pressure (hypertension), or blood fat imbalance (dyslipidemia). The different brands of semaglutide are not interchangeable. The additional advantage of semaglutide over other antidiabetic drugs is that the injections are administered just once weekly and the tablets are taken once daily.

Does semaglutide make you tired? 

• One of the common side effects of semaglutide is fatigue. Refer to the side effects listed below.

Do not use semaglutide in patients with hypersensitivity to any of its components.

• Do not use semaglutide in patients with any of the following conditions.
  • Personal or family history of medullary thyroid carcinoma (MTC)
  • Multiple endocrine neoplasia syndrome type 2 (MEN2)
• Semaglutide caused dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in rodents, however, it is not known if it can cause thyroid cancers in humans. Monitor patients routinely for the development of thyroid tumors. Apprise patients of the potential risk of thyroid carcinoma and symptoms to be alert for, and advise them to notify immediately in the event of such symptoms.
• Pancreatitis has been reported in patients receiving semaglutide. Screen patients for pancreatitis and do not initiate in patients with pancreatitis. In case a patient develops pancreatitis, discontinue semaglutide immediately.
• Semaglutide may cause or worsen diabetic retinopathy in patients with type 2 diabetes. Monitor patients with a history of diabetic retinopathy.
• If insulin or insulin secretagogues are used concurrently with semaglutide, reduce their dosage to decrease the risk of hypoglycemia.
• Semaglutide can cause acute kidney injury. Use with caution and monitor kidney function in patients with impaired kidney function and those who report severe gastrointestinal adverse reactions, especially when initiating or increasing dosage.
• There have been reports of hypersensitivity reactions, including swelling in the mucous and skin tissue (angioedema) and severe allergic reaction (anaphylaxis). Discontinue semaglutide immediately if the patient reports hypersensitivity symptoms.
• Warnings specific to Wegovy brand include the following:
  • Wegovy has been associated with gallbladder disease. Monitor patient for symptoms and treat appropriately.
  • Wegovy may increase heart rate. Monitor the patient’s heart rate regularly.
  • Wegovy may lead to suicidal ideation and behavior. Monitor the patient for depression or suicidal thoughts. Discontinue Wegovy if symptoms develop.
• Advise patients to never share their pre-filled semaglutide pens.

Common side effects of semaglutide include:

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain
• Indigestion (dyspepsia)
• Abdominal distension
• Decrease in appetite
• Belching (eructation)
• Gas (flatulence)
• Gastritis
• Gastroenteritis
• Viral gastroenteritis
• Gastroesophageal reflux disease (GERD)
• Gallstones (cholelithiasis)
• Headache
• Fatigue
• Dizziness
• Low blood glucose level (hypoglycemia)
• Severe hypoglycemia
• Diabetic retinopathy
• Bleeding in the vitreous, the gel-like substance within the eye (vitreous hemorrhage)
• Blindness
• Hair loss (alopecia)
• Antibody development
• Low blood pressure (hypotension)
• Drop in blood pressure when getting up from sitting or lying down (orthostatic hypotension)

Less common side effects of semaglutide include:

• Discomfort and redness at the site of injection
• Inflammation of the pancreas (pancreatitis)
• Increase in amylase, the enzyme that helps digest carbohydrates
• Increase in serum lipase, the enzyme that breaks down fats
• Hemorrhoids
• Biliary tract disease
• Gallbladder disease
• Inflammation of the gallbladder (cholecystitis)
• Need for removal of gallbladder (cholecystectomy)
• Acute kidney injury
• Increased heart rate
• Skin rash
• Hives (urticaria)
• Bullous pemphigoid, a rare skin disorder with fluid-filled blisters
• Severe allergic reaction (anaphylaxis)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injection, prefilled, single-dose pen (Ozempic)

• 2 mg/1.5 mL (1.34 mg/mL); delivers doses of 0.25 mg or 0.5 mg 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 tablet (Rybelsus)

• 3 mg
• 7 mg
• 14 mg

Adult:

Type 2 Diabetes Mellitus

SC (Ozempic)

• Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM)
• Also indicated to reduce risk of major adverse cardiovascular events (MACE) (e.g., cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) in adults with T2DM and established cardiovascular disease
• 0.25 mg subcutaneous (SC) once a week for 4 weeks initially; THEN increase to 0.5 mg once a week
• If glycemic control not achieved after at least 4 weeks on 0.5-mg dose, can increase to 1 mg once a week
• If glycemic control not achieved after at least 4 weeks on 1-mg dose, may increase to 2 mg once a week; not to exceed 2 mg/week
• Note: The initial 0.25-mg dose is intended for treatment initiation and is not effective for glycemic control

Oral (Rybelsus)

• Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
• Initial: 3 mg orally once daily for 30 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 orally once daily
• After 30 days on 7 mg/day: May increase dose to 14 mg orally once daily 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 (oral)

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

Weight Management

Wegovy only

• Indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m2 (obesity) or above, or 27 kg/m2 (overweight) or above in the presence of at least 1 weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, dyslipidemia)
• Initiate with low dose and gradually escalate to maintenance dose of 2.4 mg/week SC to minimize gastrointestinal (GI) adverse reactions
• If unable to tolerate a dose during escalation, consider delaying dose escalation for 4 weeks
• If unable to tolerate 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 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
• Week 13-16: 1.7 mg
• Week 17 and onward: 2.4 mg (maintenance)

Dosage Modifications

Renal or hepatic impairment

• No dosage adjustment required

Upper GI tract disease

• Oral: No dosage adjustment required

Dosing Considerations

Limitations of use

• Not studied in patients with a history of pancreatitis
• Ozempic, Rybelsus (T2DM)
  • SC semaglutide 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
• Wegovy (weight management)
  • Contains semaglutide and should not be coadministered with other semaglutide-containing products or with any other GLP-1 receptor agonist
  • Safety and effectiveness in combination with other products intended for weight loss, including prescription drugs, OTC drugs, and herbal preparations, have not been established

Pediatric:

Weight Management

Wegovy only

• Indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in pediatric patients aged 12 years or above with an initial BMI at 95th percentile or higher, standardized for age and sex (obesity)
• Refer to prescribing information for BMI cut-offs for obesity by sex and age for pediatric patients aged 12 years or above (CDC Criteria)

Once weekly SC dose escalation schedule

• Weeks 1-4: 0.25 mg SC once a week
• Weeks 5-8: 0.5 mg SC once a week
• Weeks 9-12: 1 mg SC once a week
• Week 13-16: 1.7 mg SC once a week

Maintenance dosage

• Week 17 and onward: 2.4 mg SC once a week
• Unable to tolerate maintenance 2.4 mg once-weekly dosage: May reduce maintenance dosage to 1.7 mg SC once a week
• Unable to tolerate 1.7 mg-dose: Discontinue treatment

Dosage Modifications

Renal impairment

• All severities, including end-stage renal disease: No dosage adjustment necessary

Hepatic impairment

• All severities: No dosage adjustment is necessary

Dosing Considerations

Limitations of use

Wegovy

• Do NOT combine with other semaglutide-containing products or with any other GLP-1 receptor agonist
• Safety and effectiveness in combination with other products intended for weight loss, including prescription drugs, OTC drugs, and herbal preparations, not established
• Not studied in patients with a history of pancreatitis

Overdose

• Semaglutide overdose can cause severe nausea, vomiting, and low blood glucose levels (hypoglycemia).
• Overdose is treated with symptomatic and supportive care. Patient may need to be observed and treated for a prolonged period because semaglutide effects can last for approximately one week.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Semaglutide has no listed severe or serious interactions with other drugs. 
• Semaglutide has moderate interactions with at least 23 other drugs.
• Semaglutide has no listed minor interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• Available data with use of semaglutide in pregnant women is insufficient to evaluate for drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
• Animal reproductive studies indicate semaglutide use during pregnancy may cause fetal harm.
• Poorly controlled diabetes during pregnancy can increase the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications, and fetal risks for birth defects, stillbirth, excessive birth weight (macrosomia) and associated complications.
• Semaglutide should be used during pregnancy only if potential maternal benefits justify the potential risks to the fetus.
• Women of pregnancy potential should practice effective contraception while on semaglutide therapy and the drug should be discontinued at least 2 months before a planned pregnancy.
• There is no information on the presence of semaglutide in breastmilk, its effects on milk production or on the breastfed infant. The drug is present in animal milk, and is likely also excreted in human breastmilk.
• Decision to breastfeed should be made after considering the benefits of the treatment to the mother, the benefits of breastfeeding, and the potential risk from drug exposure to the breastfed infant, in the case of injectable formulations of semaglutide. Breastfeeding is not recommended with oral semaglutide (Rybelsus brand).

• Take semaglutide exactly as prescribed.
• If you use semaglutide pens, never share them with others.
• Notify your physician immediately if you experience:
  • Symptoms of thyroid tumors, which may include a mass in the neck, swallowing difficulty, shortness of breath, or persistent hoarseness
  • Severe hypersensitivity symptoms including swelling in the face, mouth, and throat, and difficulty breathing
  • Pancreatitis symptoms such as persistent severe abdominal pain with or without vomiting
  • Nausea, vomiting, diarrhea, or dehydration
  • Worsening of diabetic retinopathy
• Inform your physician if you feel depressed or have suicidal thoughts.
• Store safely out of reach of children.
• In case of overdose, seek medical help or contact Poison Control.