Contrave Vs. Metformin: Drug Comparison

Contrave^® (naltrexone hydrochloride and bupropion hydrochloride) is a prescription medication used for weight management in adults, combining two active ingredients: naltrexone, which affects the brain's reward system, and bupropion, which influences appetite and cravings. It works by targeting the hypothalamus to reduce hunger and the mesolimbic reward system (a pathway in the brain that plays a key role in regulating feelings of pleasure, motivation, and reinforcement) to curb food cravings. Contrave is FDA-approved for chronic weight management. Common side effects include nausea, constipation, headache, and insomnia, while drug interactions can occur with MAO inhibitors, opioid pain medications, and drugs that lower the seizure threshold. Contrave carries a boxed warning for an increased risk of suicidal thoughts and behaviors, particularly in young adults, due to its bupropion component.

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.

Naltrexone: opioid antagonist

Bupropion: aminoketone antidepressant

Biguinide

Contrave (naltrexone hydrochloride and bupropion hydrochloride) is indicated:

• As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of:

  • 30 kg/m² or greater (obese)

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

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 twice daily

• Comes as 8 mg/90 mg extended-release tablets

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

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

Most common adverse reactions (greater than or equal to 5%):

• Nausea

• Constipation

• Headache

• Vomiting

• Dizziness

• Insomnia

• Dry mouth

• Diarrhea

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

• Diarrhea

• Nausea/vomiting

• Flatulence

• Weakness

• Indigestion

• Abdominal discomfort

• Headache

• Uncontrolled hypertension

• Seizure disorders, anorexia nervosa or bulimia, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs

• Use of other bupropion-containing products

• Chronic opioid use

• During or within 14 days of taking monoamine oxidase inhibitors (MAOI)

• Known allergy to any of the ingredients in Contrave

• Drug interactions: MAOIs, antidepressants (e.g., selective serotonin reuptake inhibitors and many tricyclics), antipsychotics (e.g., haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), type 1C antiarrhythmics (e.g., propafenone and flecainide), digoxin, CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel), CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin), drugs that lower seizure threshold, dopaminergic drugs (levodopa and amantadine)

• 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

• Suicidal behavior and ideation

• Neuropsychiatric adverse events during smoking cessation

• Risk of seizure may be minimized by adhering to the recommended dosing schedule and avoiding coadministration with high-fat meal

• Increase in blood pressure and heart rate

• Liver toxicity

• Angle-closure glaucoma

• Use of antidiabetic medications: Weight loss may cause hypoglycemia

• Pregnancy: Weight loss during pregnancy may cause fetal harm. Discontinue when a pregnancy is recognized

• 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: SUICIDAL THOUGHTS AND BEHAVIORS

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders. Monitor for worsening and emergence of suicidal thoughts and behaviors.

Contrave has not been studied in pediatric patients.

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 label for brand name Contrave^®. See the Full Prescribing Information for more complete information. Naltrexone and bupropion, the active ingredients in Contrave, may also be the active ingredients in other medications, and this information may not be accurate for all medications that include the active ingredients naltrexone and bupropion.

*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.