Metformin Vs. Saxenda: 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.

Saxenda^® (liraglutide) is an injectable medication used for chronic weight management in adults with obesity or overweight with at least one weight-related condition, such as hypertension, type 2 diabetes, or high cholesterol. It works by mimicking the hormone glucagon-like peptide-1 (GLP-1), which helps regulate appetite and food intake, leading to reduced caloric consumption and weight loss. Administered once daily, Saxenda is used in conjunction with a reduced-calorie diet and increased physical activity. Common side effects include nausea, diarrhea, and constipation, and it should be used with caution 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

Saxenda (liraglutide) is indicated:

• As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in:

  • Adult patients with an initial body mass index (BMI) of:

    • 30 kg/m² or greater (obese), or

    • 27 kg/m² or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia)

  • Pediatric patients aged 12 years and older with:

    • Body weight above 60 kg and

An initial BMI corresponding to 30 kg/m² for adults (obese) by international cut-offs

• 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 daily

• Comes in single-patient-use pens that deliver 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg per injection

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

• Diarrhea

• Nausea/vomiting

• Flatulence

• Weakness

• Indigestion

• Abdominal discomfort

• Headache

Most common adverse reactions, reported in greater than or equal to 5% are:

• Nausea

• Diarrhea

• Constipation

• Vomiting

• Injection site reactions

• Headache

• Low blood sugar

• Indigestion

• Fatigue

• Dizziness

• Abdominal pain

• Increased lipase

• Upper abdominal pain

• Fever

• Inflammation of the digestive system

• 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 multiple endocrine neoplasia syndrome type 2

• Hypersensitivity to liraglutide or any excipients in Saxenda

• Pregnancy

• Drug interactions: Saxenda delays gastric emptying. May impact 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

• Thyroid C-cell tumors

• Acute pancreatitis

• Acute gallbladder disease

• Low blood sugar: Can occur in adults when Saxenda is used with an insulin secretagogue (e.g., a sulfonylurea) or insulin

• Heart rate increase

• Renal impairment

• Hypersensitivity reactions

• Suicidal behavior and ideation

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

Liraglutide causes thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.

Saxenda 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 the 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 Saxenda^®. See the Full Prescribing Information for more complete information. Liraglutide, the active ingredient in Saxenda, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient liraglutide.