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Rybelsus Vs. Saxenda: Drug Comparison

Compare common side effects, interactions, warnings, and more.

Medical Review byMike Bohl, MD, MBA, MPH, MS, ALMNov 4, 2024

Medication Name

Rybelsus

*image for illustrative purpose only

Saxenda

*image for illustrative purpose only

Rybelsus

*image for illustrative purpose only

Saxenda

*image for illustrative purpose only

Summary

Prescription only

Rybelsus® (semaglutide) is an oral medication used to improve blood sugar control in adults with type 2 diabetes. It is the first glucagon-like peptide-1 (GLP-1) receptor agonist available in tablet form. It stimulates insulin secretion, inhibits glucagon release, and slows gastric emptying to lower blood sugar levels. Rybelsus is taken once daily and can be used alone or in combination with other diabetes medications, along with diet and exercise. Common side effects include nausea, diarrhea, and abdominal pain, and it should be used cautiously in patients with a history of pancreatitis.

Prescription only

Saxenda® (liraglutide) is an injectable medication used for chronic weight management in adults with obesity or overweight with at least one weight-related condition, such as hypertension, type 2 diabetes, or high cholesterol. It works by mimicking the hormone glucagon-like peptide-1 (GLP-1), which helps regulate appetite and food intake, leading to reduced caloric consumption and weight loss. Administered once daily, Saxenda is used in conjunction with a reduced-calorie diet and increased physical activity. Common side effects include nausea, diarrhea, and constipation, and it should be used with caution in patients with a history of pancreatitis​.

Drug Category

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

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

Approved Uses

Rybelsus (semaglutide) is indicated:

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

Saxenda (liraglutide) is indicated:

  • As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in:

    • Adult patients with an initial body mass index (BMI) of:

      • 30 kg/m2 or greater (obese), or

      • 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia)

    • Pediatric patients aged 12 years and older with:

      • Body weight above 60 kg and

An initial BMI corresponding to 30 kg/m2 for adults (obese) by international cut-offs

Dosage

  • Typically taken orally once daily

  • Comes in 3 mg, 7 mg, and 14 mg tablets

  • Typically taken as an injection once daily

  • Comes in single-patient-use pens that deliver 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg per injection

Known Common Side Effects

Most common adverse reactions (incidence ≥5%) are:

  • Nausea

  • Abdominal pain

  • Diarrhea

  • Decreased appetite

  • Vomiting

  • Constipation

Most common adverse reactions, reported in greater than or equal to 5% are:

  • Nausea

  • Diarrhea

  • Constipation

  • Vomiting

  • Injection site reactions

  • Headache

  • Low blood sugar

  • Indigestion

  • Fatigue

  • Dizziness

  • Abdominal pain

  • Increased lipase

  • Upper abdominal pain

  • Fever

  • Inflammation of the digestive system

Interactions & Contraindications

  • Personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2

  • Prior serious hypersensitivity reaction to semaglutide or any of the excipients in Rybelsus

  • Drug interactions: oral medications—Rybelsus delays gastric emptying

  • Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2

  • Hypersensitivity to liraglutide or any excipients in Saxenda

  • Pregnancy

  • Drug interactions: Saxenda delays gastric emptying. May impact absorption of concomitantly administered oral medications

Warnings & Precautions

  • Pancreatitis

  • Diabetic retinopathy complications

  • Low blood sugar: Concomitant use with an insulin secretagogue or insulin may increase the risk of low blood sugar, including severe low blood sugar

  • Acute kidney injury

  • Hypersensitivity reactions

  • Acute gallbladder disease

  • Pregnancy: May cause fetal harm

  • Breastfeeding: Breastfeeding not recommended

  • Females and males of reproductive potential: Discontinue Rybelsus in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide

  • Thyroid C-cell tumors

  • Acute pancreatitis

  • Acute gallbladder disease

  • Low blood sugar: Can occur in adults when Saxenda is used with an insulin secretagogue (e.g., a sulfonylurea) or insulin

  • Heart rate increase

  • Renal impairment

  • Hypersensitivity reactions

  • Suicidal behavior and ideation

Boxed Warning

WARNING: RISK OF THYROID C-CELL TUMORS

In rodents, semaglutide causes thyroid C-cell tumors. It is unknown whether Rybelsus causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined.

Rybelsus is contraindicated in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors.

WARNING: RISK OF THYROID C-CELL TUMORS

Liraglutide causes thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.

Saxenda is contraindicated in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and the symptoms of thyroid tumors.

References

*This information is from the label for brand name Rybelsus®. See the Full Prescribing Information for more complete information. Semaglutide, the active ingredient in Rybelsus, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient semaglutide.

*This information is from the label for brand name Saxenda®. See the Full Prescribing Information for more complete information. Liraglutide, the active ingredient in Saxenda, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient liraglutide.

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