Contrave Vs. Semaglutide: 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.

Semaglutide is the active ingredient in the brand-name medication Wegovy^®. The information below is about brand name Wegovy.

Wegovy (semaglutide) is an injectable medication approved 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 regulates appetite and food intake, leading to reduced calorie consumption and significant weight loss. Wegovy is administered once weekly and is intended to be used in conjunction with a reduced-calorie diet and increased physical activity. Common side effects include nausea, diarrhea, vomiting, and constipation. It should be used with caution in patients with a history of pancreatitis and is not recommended for use in pregnant or breastfeeding individuals​.

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)

Wegovy (semaglutide) is indicated in combination with a reduced calorie diet and increased physical activity:

• To reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight

• To reduce excess body weight and maintain weight reduction long term in:

  • Adults and pediatric patients aged 12 years and older with obesity

  • Adults with overweight in the presence of at least one weight-related comorbid condition

• Typically taken orally twice daily

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

• Typically taken as an injection once weekly

• Comes in single-dose pens that deliver 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, or 2.4 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 (incidence ≥5%) in adults or pediatric patients aged 12 years and older are:

• Nausea

• Diarrhea

• Vomiting

• Constipation

• Abdominal pain

• Headache

• Fatigue

• Indigestion

• Dizziness

• Abdominal distension

• Belching

• Low blood sugar in patients with type 2 diabetes

• Flatulence

• Inflammation of the digestive system

• Gastroesophageal reflux disease (heartburn)

• Inflammation of the nasal cavities and back of the throat

• 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 in patients with multiple endocrine neoplasia syndrome type 2

• Known hypersensitivity to semaglutide or any of the excipients in Wegovy

• Drug interactions: Wegovy 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

• Acute pancreatitis

• Acute gallbladder disease

• Low blood sugar: Concomitant use with insulin or an insulin secretagogue may increase the risk of low blood sugar, including severe low blood sugar

• Acute kidney injury

• Hypersensitivity reactions

• Diabetic retinopathy complications in patients with type 2 diabetes

• Heart rate increase

• Suicidal behavior and ideation

• Pregnancy: May cause fetal harm. When pregnancy is recognized, discontinue Wegovy

• Females and males of reproductive potential: Discontinue Wegovy at least 2 months before a planned pregnancy because of the long half-life of semaglutide

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

In rodents, semaglutide causes thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Wegovy causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined.

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