Contrave Vs. Saxenda: 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.

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​.

Naltrexone: opioid antagonist

Bupropion: aminoketone antidepressant

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

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)

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 twice daily

• Comes as 8 mg/90 mg extended-release 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

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

• Nausea

• Constipation

• Headache

• Vomiting

• Dizziness

• Insomnia

• Dry mouth

• Diarrhea

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

• 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)

• 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

• 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

• 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: 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: 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 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 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.