Weight Loss Medications - March 2025

Below is a list of FDA-approved weight loss medications for chronic use, ordered by percentage weight loss efficacy, with details including notable side effects, major complications or black box warnings, and contraindications. 

All data is based on FDA labeling and clinical information available as of March 12, 2025.

This is for education purposes only. This should not be considered medical advice. Please consult your doctor regarding your medical conditions and any medication that may be appropriate for you.​

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Tirzepatide (Zepbound®)

• Average Weight Loss: ~15-20% (up to 22.5% at highest dose).

• Mechanism: Dual GLP-1 and GIP receptor agonist.

• Approval: Adults only (approved November 2023).

• Notable Side Effects: Nausea, diarrhea, vomiting, constipation, abdominal pain, injection-site reactions, fatigue, decreased appetite.

• Major Complications/Black Box Warnings:

  • Boxed Warning: Risk of thyroid C-cell tumors (observed in rodents; human risk unclear).

  • Potential for pancreatitis, gallbladder disease (e.g., gallstones), hypoglycemia (especially with diabetes meds), kidney injury (from dehydration due to GI side effects).

• Contraindications: Personal or family history of medullary thyroid carcinoma (MTC), Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), hypersensitivity to tirzepatide.

• Notes: Avoid in pregnancy; monitor for depression or suicidal thoughts (rare but reported).​​

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Semaglutide (Wegovy®)

• Average Weight Loss: ~12-15% (up to 17% in trials).

• Mechanism: GLP-1 receptor agonist.

• Approval: Adults and adolescents 12+.

• Notable Side Effects: Nausea, vomiting, diarrhea, constipation, abdominal pain, headache, fatigue, dyspepsia, injection-site reactions.

• Major Complications/Black Box Warnings:

  • Boxed Warning: Risk of thyroid C-cell tumors (rodent studies; human relevance uncertain).

  • Pancreatitis, gallbladder issues (e.g., cholelithiasis), acute kidney injury (from dehydration), increased heart rate, rare diabetic retinopathy worsening.

• Contraindications: Personal or family history of MTC, MEN 2, hypersensitivity to semaglutide.

• Notes: Not recommended in pregnancy; caution with history of depression or suicidal behavior.​

Phentermine-Topiramate (Qsymia®)

• Average Weight Loss: ~8-10% (up to 11% at highest dose).

• Mechanism: Appetite suppressant + satiety enhancer.

• Approval: Adults and adolescents 12+.

• Notable Side Effects: Dry mouth, constipation, insomnia, dizziness, paresthesia (tingling), taste changes, mood changes (e.g., anxiety, irritability).

• Major Complications/Black Box Warnings:

  • Boxed Warning: Fetal toxicity—risk of birth defects (e.g., cleft lip/palate) if used during pregnancy.

  • Increased heart rate, potential for abuse (phentermine is a stimulant), metabolic acidosis, kidney stones, cognitive impairment (e.g., memory issues), glaucoma risk.

• Contraindications: Pregnancy, glaucoma, hyperthyroidism, recent MAO inhibitor use, hypersensitivity to components.

• Notes: Requires Risk Evaluation and Mitigation Strategy (REMS) due to teratogenicity; avoid alcohol (increases seizure risk).​

Liraglutide (Saxenda®)

• Average Weight Loss: ~5-8% (up to 9% in some patients).

• Mechanism: GLP-1 receptor agonist.

• Approval: Adults and adolescents 12+.

• Notable Side Effects: Nausea, vomiting, diarrhea, constipation, headache, injection-site reactions, low blood sugar (with other diabetes meds).

• Major Complications/Black Box Warnings:

  • Boxed Warning: Risk of thyroid C-cell tumors (rodent data; human risk unclear).

  • Pancreatitis, gallbladder disease, renal impairment (from dehydration), rare suicidal thoughts.

• Contraindications: Personal or family history of MTC, MEN 2, hypersensitivity to liraglutide, pregnancy.

• Notes: Monitor for signs of thyroid tumors or depression.

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Naltrexone-Bupropion (Contrave®)​

• Average Weight Loss: ~4-5% (up to 6-9% in responders).

• Mechanism: Appetite and craving reduction.

• Approval: Adults only.

• Notable Side Effects: Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, diarrhea.

• Major Complications/Black Box Warnings:

• Boxed Warning: Increased risk of suicidal thoughts and behavior (due to bupropion, especially in young adults).

• Seizure risk (bupropion lowers seizure threshold), neuropsychiatric reactions, hepatotoxicity (naltrexone), elevated blood pressure/heart rate.

• Contraindications: Uncontrolled hypertension, seizure disorders, eating disorders (e.g., bulimia), chronic opioid use, recent MAO inhibitor use, pregnancy, hypersensitivity.

• Notes: Avoid with high-fat meals (increases absorption, side effects); caution with alcohol.​

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Orlistat (Xenical/Alli®)​

• Average Weight Loss: ~3-5% (Xenical: ~5%, Alli: ~3%).

• Mechanism: Lipase inhibitor.

• Approval: Adults and children 12+ (Xenical); adults only (Alli OTC).

• Notable Side Effects: Oily stools, flatulence, fecal urgency/incontinence, abdominal pain, reduced absorption of fat-soluble vitamins (A, D, E, K).

• Major Complications/Black Box Warnings:

• No boxed warning.

• Rare liver injury (hepatotoxicity), kidney stones (oxalate-related), potential malabsorption issues long-term.

• Contraindications: Chronic malabsorption syndrome, cholestasis (gallbladder obstruction), hypersensitivity to orlistat, pregnancy.

• Notes: Take with multivitamin to offset vitamin loss; side effects worse with high-fat diets.​

Setmelanotide (Imcivree®)

• Average Weight Loss: ~10-12% (variable, specific to genetic conditions).

• Mechanism: MC4 receptor agonist.

• Approval: Adults and children 6+ with POMC, PCSK1, or LEPR deficiency.

• Notable Side Effects: Hyperpigmentation (skin darkening), injection-site reactions, nausea, headache, diarrhea, back pain, fatigue.

• Major Complications/Black Box Warnings:

  • No boxed warning.

  • Depression or suicidal thoughts (rare), sexual adverse reactions (e.g., spontaneous erections), potential long-term risks unclear due to rarity.

• Contraindications: Hypersensitivity to setmelanotide; not indicated for general obesity.

• Notes: For rare genetic obesity only; monitor skin changes and mood.​

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General Observations:

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• GLP-1 Drugs (Tirzepatide, Semaglutide, Liraglutide): Share a thyroid tumor risk warning, common GI side effects, and contraindications related to MTC/MEN 2.

• Stimulant-Based (Phentermine-Topiramate): Higher risk of cardiovascular and fetal harm concerns.

• Naltrexone-Bupropion: Unique psychiatric and seizure risks due to bupropion.

• Orlistat: Stands out for GI-specific side effects tied to fat malabsorption.

• Setmelanotide: Tailored to rare conditions, with skin pigmentation as a signature side effect.

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Caveats:

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• Individual Variation: Side effects and efficacy differ widely; some patients tolerate drugs better than others.

• Pregnancy: Most are contraindicated due to unknown or confirmed fetal risks.

• Monitoring: All require medical oversight, especially for major complications like pancreatitis or suicidal ideation.

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For the latest updates or personalized advice, consult a healthcare provider or the FDA’s drug labeling database.

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