Letrozole Vs. Metformin: Drug Comparison

Letrozole is an aromatase inhibitor used to treat hormone receptor-positive breast cancer by lowering estrogen levels, which helps slow the growth of cancer cells that rely on estrogen. Its FDA-approved indications include the treatment of postmenopausal women with early breast cancer, advanced breast cancer, or as adjuvant therapy to reduce the risk of recurrence. Off-label uses may include ovarian stimulation for infertility in women with polycystic ovary syndrome (PCOS). Letrozole is available in tablet form, taken orally. Common side effects include hot flashes, joint pain, dizziness, and fatigue, while serious risks include bone loss and an increased risk of cardiovascular events. Caution is advised in patients with osteoporosis or heart disease.

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.

Aromatase inhibitor

Biguinide

Letrozole is indicated for:

• Adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer

• Extended adjuvant treatment of postmenopausal women with early breast cancer who have received prior standard adjuvant tamoxifen therapy

• First and second-line treatment of postmenopausal women with hormone receptor positive or unknown advanced breast cancer

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

• Typically taken orally once daily or every other day

• Comes in 2.5 mg tablets

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

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

The most common adverse reactions (greater than 20%) were:

• Hot flashes

• Joint pain

• Flushing

• Weakness

• Swelling

• Headache

• Dizziness

• High blood cholesterol

• Sweating increased

• Bone pain

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

• Diarrhea

• Nausea/vomiting

• Flatulence

• Weakness

• Indigestion

• Abdominal discomfort

• Headache

• Pregnancy

• Known hypersensitivity to the active substance, or to any of the excipients

• 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

• Decreases in bone mineral density may occur

• Increases in total cholesterol may occur

• Fatigue, dizziness, and sleepiness may occur

• Embryo-fetal toxicity

• Breastfeeding: Advise not to breastfeed

• 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

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.

*This information is from the letrozole label used by Avet Pharmaceuticals Inc. See the Full Prescribing Information for more complete information. This information may not be accurate for all medications that include the active ingredient letrozole.

*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.