11/10/2025
💊 Adipex, Contrave, and Qsymia: The Oral Medications and What They Really Deliver
- Tyler Perrin-Bellelo, MD
Obesity Medicine | Internal Medicine
These are the oral anti-obesity medications that live in the lower to mid-range of the weight-loss curve. They’re effective when we’re targeting ~5–9% total body-weight reduction, especially when matched to the right patient.
✅ FDA Indications
All anti-obesity medications — including these — are approved for:
• BMI ≥ 30, or
• BMI ≥ 27 with a weight-related medical condition
(hypertension, diabetes, prediabetes, PCOS, sleep apnea, fatty liver, dyslipidemia, etc.)
These are medical treatments for a medical disease!
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✅ Effectiveness: How Much Weight Loss They Produce
Phentermine (Adipex)
• Short-term only: 12 weeks (3 months)
• Average weight loss: ~5% (real-world closer to 3–4%)
• Works through norepinephrine-driven appetite suppression
Contraindications: pregnancy, heart disease, uncontrolled hypertension, hyperthyroidism, glaucoma, MAOIs, substance-use history.
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Contrave (Naltrexone/Bupropion)
• Long-term medication
• Average weight loss: ~5–6% at one year
• 42–55% achieve ≥5% TBWL
• Especially helpful for cravings and reward-driven eating
Important:
Contrave has one of the highest discontinuation rates among oral agents — even higher than GLP-1s — almost always due to nausea.
Contraindications: seizure disorder, uncontrolled hypertension, eating disorders, opioid use, pregnancy, MAOIs.
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Qsymia (Phentermine/Topiramate)
• Long-term medication
• Most effective oral agent: ~6.6–8.8% (sometimes 8–11%)
• 70–75% achieve ≥5% TBWL
• Strongest overall response
Contraindications: pregnancy (teratogenic), trying to conceive, kidney stones, acute angle-closure glaucoma, hyperthyroidism, MAOIs.
Patient note:
Topiramate affects carbonic anhydrase — it makes carbonated drinks taste awful. Soda drinkers feel this immediately.
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✅ Tolerability & Real-World Discontinuation
The real truth: the medications that produce the most weight loss often have higher drop-off rates.
Highest discontinuation:
• Contrave: nausea, neuropsychiatric effects
• Qsymia: taste changes, cognitive slowing, paresthesias, kidney stones
Serious adverse events are rare, but tolerability drives real-world adherence — especially in the first few months.
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✅ Cardiometabolic Benefits — and Their Limits
All three oral agents can improve:
• waist circumference
• fasting glucose
• HbA1c
• blood pressure
• inflammation
But:
❌ None have proven reductions in cardiovascular events or mortality.
• Qsymia improves weight and glycemia but has minimal lipid effects and no proven CV event reduction.
• Contrave improves HDL slightly but shows no reduction in CV events or mortality in long-term studies.
• Phentermine has no long-term cardiovascular outcome data.
This is very different from GLP-1 medications, which do have cardiovascular benefit, especially in diabetes and now in some non-diabetic populations.
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✅ Quality of Life & Mood
• All three modestly improve quality-of-life scores.
• Contrave may cause a slight increase in depressive symptoms (not clinically significant).
• Qsymia and Adipex are generally neutral to mildly positive in mood effects.
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✅ The Bottom Line
• Qsymia gives the highest percentage weight loss among oral agents.
• Contrave is excellent for cravings but has the highest nausea-driven discontinuation.
• Adipex is short-term and more modest.
All three can help patients achieve a clinically meaningful 5–9% weight loss, improving blood pressure, blood sugar, inflammation, and fatty liver.
Next, we move into the GLP-1 medications — where the average percentage of weight loss climbs dramatically and the metabolic and cardiovascular data become even stronger.
