| Diabetes Mellitus, Non-Insulin-Dependent

Rybelsus vs Xultophy

Side-by-side clinical, coverage, and cost comparison for diabetes mellitus, non-insulin-dependent.
Deep comparison between: Ozempic vs Xultophy 100/3.6 with Prescriber.AI
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Safety signalsXultophy 100/3.6 has a higher rate of injection site reactions vs Ozempic based on FDA-approved prescribing information
Coverage gaps3 major payers require step therapy for Xultophy 100/3.6 but not Ozempic, including UnitedHealthcare
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Ozempic
Xultophy 100/3.6
At A Glance
Oral
Daily
GLP-1 receptor agonist
SC injection
Once daily
Basal insulin/GLP-1 receptor agonist combination
Indications
  • Diabetes Mellitus, Non-Insulin-Dependent
  • Diabetes Mellitus, Non-Insulin-Dependent
Dosing
Diabetes Mellitus, Non-Insulin-Dependent Starting dose 1.5 mg orally once daily for 30 days (not effective for glycemic control); escalate to 4 mg once daily days 31-60; maintain at 4 mg or increase to 9 mg once daily if additional glycemic control is needed. Take on an empty stomach in the morning with up to 4 oz water; wait at least 30 minutes before eating, drinking, or taking other oral medications.
Diabetes Mellitus, Non-Insulin-Dependent Patients naive to basal insulin or GLP-1 receptor agonist: start 10 units SC once-daily; patients currently on basal insulin or GLP-1 receptor agonist: start 16 units SC once-daily (discontinue prior therapy first); titrate by 2 units once or twice weekly based on fasting plasma glucose; maximum 50 units/day.
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 excipient in OZEMPIC tablets
  • Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
  • Episodes of hypoglycemia
  • Hypersensitivity to insulin degludec, liraglutide, or any excipient in Xultophy 100/3.6
Adverse Reactions
Most common (>=5%) nausea, abdominal pain, diarrhea, decreased appetite, vomiting, constipation
Serious risk of thyroid C-cell tumors, acute pancreatitis, diabetic retinopathy complications, hypoglycemia with concomitant insulin secretagogues or insulin, acute kidney injury due to volume depletion, severe gastrointestinal reactions, hypersensitivity reactions, acute gallbladder disease, pulmonary aspiration during general anesthesia or deep sedation
Postmarketing acute and necrotizing pancreatitis, ileus, intestinal obstruction, anaphylaxis, angioedema, rash, urticaria, cholecystitis, cholelithiasis requiring cholecystectomy, dizziness, dysesthesia, dysgeusia, headache, pulmonary aspiration, acute kidney injury, alopecia
Most common (>=5%) Nasopharyngitis, headache, nausea, diarrhea, increased lipase, upper respiratory tract infection, hypoglycemia
Serious Thyroid C-cell tumors, acute pancreatitis, hypoglycemia, acute kidney injury, severe gastrointestinal reactions, hypersensitivity reactions including anaphylaxis, acute gallbladder disease, hypokalemia, pulmonary aspiration
Postmarketing Localized cutaneous amyloidosis, acute and necrotizing pancreatitis, hepatitis, cholecystitis, angioedema, anaphylactic reactions, medullary thyroid carcinoma, acute renal failure, alopecia
Pharmacology
Semaglutide is a GLP-1 receptor agonist (GLP-1 analogue with 94% sequence homology to human GLP-1) that selectively binds to and activates the GLP-1 receptor, stimulating glucose-dependent insulin secretion and inhibiting glucagon secretion to lower blood glucose, with a minor delay in early postprandial gastric emptying; its long half-life results from albumin binding and stabilization against DPP-4 degradation.
Xultophy 100/3.6 combines insulin degludec, a long-acting basal insulin analog that lowers blood glucose by stimulating peripheral glucose uptake and inhibiting hepatic glucose production, with liraglutide, a GLP-1 receptor agonist that increases glucose-dependent insulin release, decreases glucagon secretion, and slows gastric emptying.
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Most Common Insurance
Anthem BCBS
Ozempic
  • Covered on 5 commercial plans
  • PA (12/12) · Step Therapy (10/12) · Qty limit (11/12)
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Xultophy 100/3.6
  • Covered on 5 commercial plans
  • PA (5/12) · Step Therapy (7/12) · Qty limit (9/12)
View full coverage details ›
UnitedHealthcare
Ozempic
  • Covered on 4 commercial plans
  • PA (8/8) · Step Therapy (0/8) · Qty limit (8/8)
View full coverage details ›
Xultophy 100/3.6
  • Covered on 4 commercial plans
  • PA (0/8) · Step Therapy (0/8) · Qty limit (1/8)
View full coverage details ›
Humana
Ozempic
  • Covered on 0 commercial plans
  • PA (3/3) · Step Therapy (1/3) · Qty limit (3/3)
View full coverage details ›
Xultophy 100/3.6
  • Covered on 0 commercial plans
  • PA (3/3) · Step Therapy (3/3) · Qty limit (3/3)
View full coverage details ›
Coverage data sourced from MMIT. Updated monthly.
Savings
No savings programs available for Ozempic.
No savings programs available for Xultophy 100/3.6.
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Clinical data sourced from FDA-approved labeling. Coverage data via MMIT. Updated monthly.