Metformin Vs. Mounjaro: 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.

Mounjaro^® (tirzepatide) is an injectable medication used to treat type 2 diabetes by improving blood sugar control and promoting weight loss. It functions by activating two receptors, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which enhance insulin secretion and slow gastric emptying. Mounjaro is administered once weekly, with dose adjustments made based on the patient's response. Common side effects include nausea, diarrhea, and decreased appetite. It should be used with caution in individuals with a history of thyroid cancer or multiple endocrine neoplasia syndrome type 2​.

Biguinide

Glucose-dependent insulinotropic polypeptide (GIP) receptor and 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

Mounjaro (tirzepatide) 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 as an injection once weekly

• Comes in 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg per 0.5 mL single-dose pens or single-dose vials

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

• Diarrhea

• Nausea/vomiting

• Flatulence

• Weakness

• Indigestion

• Abdominal discomfort

• Headache

The most common adverse reactions, reported in ≥5% of patients treated with Mounjaro are:

• Nausea

• Diarrhea

• Decreased appetite

• Vomiting

• Constipation

• Indigestion

• Abdominal pain

• 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

• Known serious hypersensitivity to tirzepatide or any of the excipients in Mounjaro

• Drug interactions: Mounjaro delays gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications

• 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

• Low blood sugar with concomitant use of insulin secretagogues or insulin

• Hypersensitivity reactions

• Acute kidney injury

• Severe gastrointestinal disease

• Diabetic retinopathy complications in patients with a history of diabetic retinopathy

• Acute gallbladder disease

• Pregnancy: Based on animal study, may cause fetal harm

• Females of reproductive potential: Females using oral contraceptives should consider switching to a non-oral contraceptive method or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation

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

Tirzepatide causes thyroid C-cell tumors in rats. It is unknown whether Mounjaro causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of tirzepatide-induced rodent thyroid C-cell tumors has not been determined.

Mounjaro 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 Mounjaro. See the Full Prescribing Information for more complete information. Tirzepatide, the active ingredient in Mounjaro, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient tirzepatide.