Oral Semaglutide (Rybelsus) | Drug Digest

Pharmacologic Category (Oral Diabetes Medicine): Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist

Mechanism of Action: Stimulates insulin release in the presence of elevated blood glucose. Suppresses Glucagon (inhibits hepatic glucose production); thereby reducing both fasting and postprandial glucose. It delays gastric emptying (slower absorption of sugar and promotes the feeling of fullness).

FDA Labeled Indications: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

  • May be used as an adjunctive agent or alternative monotherapy for patients in whom initial therapy with lifestyle intervention and metformin failed or those who cannot take metformin.
  • Due to lack of additive glycemic benefit, avoid concomitant use with a dipeptidyl peptidase-4 inhibitor.
  • May require a dose reduction of insulin and/or insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia.

Administration: Administer on an empty stomach, ≥30 minutes before the first food, beverage, or other oral medications of the day with ≤4 oz of plain water only. The manufacturer recommends eating 30 to 60 minutes after the dose. Swallow tablets whole; do not split, crush, or chew.

Dosing: Initial: 3 mg once daily for 30 days, then increase to 7 mg once daily; may increase to 14 mg once daily after 30 days on the 7 mg dose if needed to achieve glycemic goals. The lower initial dose (3 mg daily) is intended to reduce GI symptoms; it does not provide effective glycemic control.

Dosing for Kidney Impairment:
Mild to severe impairment: No dosage adjustment necessary. Use caution when initiating or escalating doses; new-onset or worsening of existing renal failure has been reported, most commonly in patients experiencing volume depletion from GI losses (e.g., vomiting, diarrhea, dehydration).

  • Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzable: No supplemental dose or dosage adjustment necessary; use with caution due to limited clinical evidence.
  • Peritoneal dialysis: Unlikely to be dialyzable: No dosage adjustment necessary; use with caution due to limited clinical evidence.

Dosing for Hepatic Impairment: No dosage adjustment necessary.

Contraindications:
Hypersensitivity to semaglutide or any component of the formulation, personal or family history of medullary thyroid carcinoma (MTC), patients with multiple endocrine neoplasia syndrome type 2 (MEN2), pregnancy, breastfeeding, history of pancreatitis. Do not use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis (not a substitute for insulin).

Notes:

  • Most common adverse reactions are GI side effects: nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation. Start low and go slow!
  • Not FDA approved for weight management.


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