Metformin Vs. Rybelsus: Drug Comparison

Metformin is an oral medication commonly prescribed to manage blood sugar levels in individuals with type 2 diabetes. It works by decreasing glucose production in the liver, improving the body's sensitivity to insulin, and reducing the amount of sugar absorbed by the intestines. Metformin is often used as a first-line treatment due to its efficacy, safety profile, and additional benefits, such as weight stabilization and low risk of low blood sugar. Common side effects include gastrointestinal issues like nausea, diarrhea, and abdominal discomfort.

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.

Biguinide

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

Metformin hydrochloride tablets are indicated:

• As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus

Rybelsus (semaglutide) is indicated:

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

• Typically taken orally once, twice, or three times daily

• Comes in 500 mg, 850 mg, and 1,000 mg tablets

• Typically taken orally once daily

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

For metformin hydrochloride, the most common adverse reactions (>5%) are:

• Diarrhea

• Nausea/vomiting

• Flatulence

• Weakness

• Indigestion

• Abdominal discomfort

• Headache

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

• Nausea

• Abdominal pain

• Diarrhea

• Decreased appetite

• Vomiting

• Constipation

• Severe renal impairment (eGFR below 30 mL/min/1.73 m²)

• Hypersensitivity to metformin

• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma

• Drug interactions: Carbonic anhydrase inhibitors, drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine), alcohol

• 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

• Lactic acidosis: See Boxed Warning

• Vitamin B12 deficiency: Metformin may lower vitamin B12 levels

• Low blood sugar with concomitant use with insulin and insulin secretagogues

• Females and males of reproductive potential: Potential for an unintended pregnancy

• 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

WARNING: LACTIC ACIDOSIS

Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.

Risk factors include renal impairment, concomitant use of certain drugs, age >65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the Full Prescribing Information.

If lactic acidosis is suspected, discontinue metformin hydrochloride tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

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.

*This information is from the metformin hydrochloride label used by Epic Pharma, LLC. See the Full Prescribing Information for more complete information. Metformin may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient metformin.

*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.