Three prescription weight-loss drugs predate the GLP-1s and are still in use: phentermine, Qsymia (phentermine plus topiramate) and Contrave (naltrexone plus bupropion).
They are cheaper, they are older, and they are frequently what an insurer offers when it declines a GLP-1. They also work on a completely different premise, and one feature of that premise is worth understanding before anything else.
All three come with an expiry test. GLP-1s do not.
This is the structural difference, and it is written into the labels rather than being a matter of clinical style.
| Drug | What the label says about stopping |
|---|---|
| Phentermine | Indicated as a short-term (a few weeks) adjunct. It was never a long-term drug. |
| Qsymia | After 12 weeks at the top dose, if the patient has not lost at least 5% of baseline body weight, discontinue. |
| Contrave | After 12 weeks at the maintenance dose, if the patient has not lost at least 5% of baseline body weight, discontinue. |
The Qsymia wording is unusually direct: discontinue, "as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment." Contrave's is near-identical.
No GLP-1 label contains an equivalent instruction. That is not because GLP-1s always work — they do not — but because the trial data supported open-ended use in a way these drugs' data did not.
What it means in practice: starting one of these is starting a twelve-week trial with a defined failure condition, not starting a treatment. Knowing that in advance changes how the first three months feel.
Phentermine
The oldest of the three and by far the most prescribed, largely because it is inexpensive.
- What it is: a sympathomimetic amine, related chemically and pharmacologically to the amphetamines in the label's own words. It is a Schedule IV controlled substance.
- Approved for: short-term (a few weeks) use in obesity, at BMI ≥ 30, or ≥ 27 with a risk factor such as controlled hypertension, diabetes or hyperlipidaemia.
- Usual dose: one 37.5 mg tablet daily, before breakfast or one to two hours after. With or without food.
- Timing matters: the label says to avoid late-evening administration because of insomnia risk.
- Kidney adjustment: limit to 15 mg daily in severe renal impairment (eGFR 15–29).
Who cannot take it
The contraindication list is broad and cardiovascular concerns dominate it: any history of cardiovascular disease — coronary artery disease, stroke, arrhythmias, congestive heart failure, uncontrolled hypertension — plus MAOI use within 14 days, hyperthyroidism, glaucoma, agitated states, a history of drug abuse, pregnancy, nursing, and known hypersensitivity to sympathomimetic amines.
The dependence question
Worth being straight about, because it is the thing people most often are not told. The label states that amphetamines and related stimulants "have been extensively abused", that abuse "may be associated with intense psychological dependence and severe social dysfunction", and that there are reports of patients escalating doses to many times those recommended.
That is not a reason to refuse the drug. It is a reason the prescription is short by design and why it is scheduled.
Qsymia (phentermine + topiramate)
Phentermine combined with topiramate, an anti-seizure drug that independently suppresses appetite. Approved for adults and children aged 12 and over, which is a wider age range than most people expect.
The dose ladder
Four strengths, and the escalation has decision points built into it:
| Step | Dose (phentermine/topiramate) | Duration |
|---|---|---|
| 1 | 3.75 mg / 23 mg | 14 days |
| 2 | 7.5 mg / 46 mg | 12 weeks, then assess |
| 3 | 11.25 mg / 69 mg | 14 days — only if less than 3% lost |
| 4 | 15 mg / 92 mg | 12 weeks, then the 5% decision |
So there are two gates, not one. At 12 weeks on 7.5/46 you either lost 3% and stay, or you escalate. At 12 weeks on 15/92 you either lost 5% or you stop.
You cannot simply stop taking it
This is the single most important practical fact on this page, and it is the sharpest contrast with a GLP-1.
From the label: discontinue 15 mg/92 mg gradually, taking it once daily every other day for at least one week before stopping altogether, "due to the possibility of precipitating a seizure."
That is the topiramate. Anti-seizure drugs are tapered, not dropped. If you run out, lose the prescription, or decide mid-week that you are done, this is a conversation with a prescriber rather than a decision you make alone.
Pregnancy: a REMS and monthly testing
Qsymia is distributed under a Risk Evaluation and Mitigation Strategy, meaning only certified pharmacies may dispense it. The reason is teratogenicity: the data indicate increased risk of major congenital malformations, including cleft lip and cleft palate, and of being small for gestational age.
Consequently a negative pregnancy test is recommended before starting and monthly during treatment for anyone who can become pregnant. Pregnancy is an outright contraindication.
Side effects
From the label, adults at 15 mg/92 mg against placebo:
| Adverse reaction | Qsymia 15/92 | Placebo |
|---|---|---|
| Paraesthesia (tingling, pins and needles) | 20% | 2% |
| Dry mouth | 19% | 3% |
| Constipation | 16% | 6% |
| Dysgeusia (altered taste) | 9% | 1% |
| Insomnia | 9% | 5% |
| Dizziness | 9% | 3% |
Paraesthesia at one in five is the signature. It is a topiramate effect, it is usually harmless, and it is not something GLP-1 users encounter — so it is worth recognising rather than being alarmed by.
Other contraindications: glaucoma, hyperthyroidism, MAOI use within 14 days, and known hypersensitivity.
Contrave (naltrexone + bupropion)
The mechanism is different again. Bupropion is an antidepressant that affects dopamine and noradrenaline; naltrexone is an opioid receptor antagonist used in addiction treatment. Together they act on reward pathways rather than on satiety hormones.
Which makes Contrave the closest thing available to a drug aimed at food noise by a route other than a GLP-1.
The boxed warning
Contrave carries one, and it comes from the bupropion. The label states that Contrave is not approved for treating major depressive disorder or other psychiatric disorders, and that antidepressants increased the risk of suicidal thoughts and behaviour in children, adolescents and young adults. Monitoring for worsening mood and for emergent suicidal thoughts is required.
Anyone with a psychiatric history should be raising it before starting, not after.
The dose ladder
One tablet strength — 8 mg naltrexone / 90 mg bupropion — built up over four weeks:
| Week | Morning | Evening |
|---|---|---|
| 1 | 1 tablet | — |
| 2 | 1 tablet | 1 tablet |
| 3 | 2 tablets | 1 tablet |
| 4 onward | 2 tablets | 2 tablets |
Maintenance is 32 mg naltrexone / 360 mg bupropion daily. The 12-week clock starts from reaching maintenance, not from the first tablet.
The opioid problem
This deserves its own heading because the consequence is fatal rather than inconvenient.
Contrave must not be given to anyone on chronic opioids, because naltrexone blocks opioid receptors. And the label is explicit about what happens if someone tries to push through that blockade: attempting to overcome it with large doses of opioids "may lead to a fatal overdose."
That includes prescribed opioids for chronic pain, not only illicit use. Acute opioid withdrawal is also a contraindication.
Everything else that rules it out
Contrave has the longest contraindication list of the three: uncontrolled hypertension; any seizure disorder or history of seizures; any other bupropion-containing product; bulimia or anorexia nervosa; chronic opioid use or acute opioid withdrawal; abrupt discontinuation of alcohol, benzodiazepines, barbiturates or antiepileptic drugs; MAOI use within 14 days; and known allergy to the components.
The bupropion-containing-product line catches people, because bupropion is also sold for depression and for smoking cessation under other names. Taking both is doubling the dose.
Side effects
| Adverse reaction | Contrave | Placebo |
|---|---|---|
| Nausea | 32.5% | 6.7% |
| Constipation | 19.2% | 7.2% |
| Headache | 17.6% | 10.4% |
| Vomiting | 10.7% | 2.9% |
| Dizziness | 9.9% | 3.4% |
| Insomnia | 9.2% | 5.9% |
Nausea at nearly a third is the headline, and it is worth noting that this is the same dominant complaint GLP-1 users report — by an entirely different mechanism.
How much weight do they take off?
Being straight with you: neither the Qsymia nor the Contrave label publishes a mean weight-loss figure. Both give only the 5% threshold used for the stop decision, and Qsymia adds a 3% threshold for dose escalation.
We are not going to fill that gap with numbers from elsewhere and present them as label facts. What the labels do tell you is the shape of the expectation: a drug whose continuation test is "did you lose 5% in twelve weeks" is not a drug that expects 20%.
For comparison, the figures that are in labels: tirzepatide about 20.9% over 72 weeks, semaglutide about 14.9% over 68 weeks, orforglipron 11.1% at the maximum dose. See GLP-1 weight loss results by drug.
So when does one of these make sense?
Three situations, honestly:
- Cost. These are old drugs and phentermine in particular is cheap. If a GLP-1 is unaffordable and the routes in our cost guide do not close the gap, this is a real alternative rather than a consolation.
- Coverage. Many plans require a documented trial of an older agent before approving a GLP-1. Knowing the 12-week rule matters here, because a failed trial is itself the documentation.
- Mechanism. Contrave targets reward rather than satiety. For someone whose difficulty is cravings rather than portion size, that is a different lever, not a weaker one.
And when they do not: if you cannot take stimulants for cardiovascular reasons, phentermine and Qsymia are both out. If you are on opioids or have a seizure history, Contrave is out. Those exclusions remove a large number of people, which is part of why the GLP-1s displaced these drugs so quickly.
This article is general information, not medical advice. Indications, dose ladders, stop rules, taper instructions, contraindications and adverse-reaction percentages were read from the FDA labelling on 5 August 2026 — Qsymia and Contrave via DailyMed, phentermine via the openFDA label API. Labels are revised; confirm against the leaflet supplied with your prescription. All three of these drugs have exclusions that make them unsafe for substantial groups of people, and deciding between them and a GLP-1 is a clinical judgement that needs your own history in front of it.
Scientific References
3 sources- 1
VIVUS LLC
QSYMIA (phentermine and topiramate) extended-release capsule — prescribing information
DailyMed, U.S. National Library of Medicine · 2026
NIH - 2
Nalpropion Pharmaceuticals
CONTRAVE extended-release (naltrexone hydrochloride and bupropion hydrochloride) tablet — prescribing information
DailyMed, U.S. National Library of Medicine · 2026
NIH - 3
U.S. Food and Drug Administration
Phentermine hydrochloride tablets — prescribing information (openFDA label API)
U.S. Food and Drug Administration · 2026
References open in a new tab. Content is reviewed against peer-reviewed literature as part of our editorial policy.
About the author
Editor, Modern Weight Science
Claudiu Gheorghe is the editor of Modern Weight Science. He is not a physician. His role is to synthesize peer-reviewed studies, clinical-trial data, and FDA prescribing information into clear, plain-language explanations, and to make sure every factual claim on the site traces back to a cited source. Any decision about starting, changing, or stopping a medication belongs with a licensed clinician who knows your history.
Every claim is checked against peer-reviewed research through our review process and fact-checking policy.
Frequently Asked Questions
What is phentermine and how is it taken?
Phentermine is a sympathomimetic amine that the FDA labelling describes as related chemically and pharmacologically to the amphetamines. It is a Schedule IV controlled substance approved as a short-term adjunct — the label says a few weeks — for obesity at a BMI of 30 or above, or 27 with a risk factor such as controlled hypertension, diabetes or hyperlipidaemia. The usual adult dose is one 37.5 mg tablet daily, taken before breakfast or one to two hours after, and the label advises avoiding late-evening doses because of insomnia.
What are the side effects of Qsymia?
At the 15 mg/92 mg dose against placebo, the label reports paraesthesia — tingling or pins and needles — in 20% against 2%, dry mouth 19% against 3%, constipation 16% against 6%, altered taste 9% against 1%, insomnia 9% against 5% and dizziness 9% against 3%. Paraesthesia is the signature effect and comes from the topiramate component.
Can you stop taking Qsymia suddenly?
No. The label instructs that 15 mg/92 mg be discontinued gradually, taken once daily every other day for at least one week before stopping altogether, because of the possibility of precipitating a seizure. That comes from the topiramate, which is an anti-seizure drug. This is the sharpest practical difference from a GLP-1, which can be stopped at any point. Running out of a prescription is therefore a conversation with a prescriber rather than a decision to make alone.
What is the Contrave dosing schedule?
One tablet contains 8 mg naltrexone and 90 mg bupropion, built up over four weeks: week 1 is one tablet in the morning only, week 2 is one morning and one evening, week 3 is two morning and one evening, and from week 4 onward it is two morning and two evening — a maintenance dose of 32 mg naltrexone and 360 mg bupropion daily. The 12-week assessment clock starts from reaching maintenance, not from the first tablet.
Why do Qsymia and Contrave tell you to stop after 12 weeks?
Because both labels contain an explicit continuation test. If a patient has not lost at least 5% of baseline body weight after 12 weeks at the relevant dose, the label says to discontinue, since it is unlikely they will achieve and sustain clinically meaningful weight loss with continued treatment. No GLP-1 label contains an equivalent instruction. In practice it means starting one of these drugs is starting a twelve-week trial with a defined failure condition rather than starting an open-ended treatment.
Can you take Contrave if you use opioids?
No. Chronic opioid use is a contraindication because naltrexone blocks opioid receptors, and the label warns that attempting to overcome that blockade with large doses of opioids may lead to a fatal overdose. This applies to prescribed opioids for chronic pain as well as illicit use. Acute opioid withdrawal is also a contraindication.
How much weight do phentermine, Qsymia and Contrave cause?
Neither the Qsymia nor the Contrave label publishes a mean weight-loss percentage. Both give only the 5% threshold used for the 12-week stop decision, and Qsymia adds a 3% threshold for dose escalation. What that implies is worth taking seriously: a drug whose continuation test is 5% in twelve weeks is not a drug that expects 20%. By comparison, the labelled figures for GLP-1s are roughly 20.9% for tirzepatide over 72 weeks, 14.9% for semaglutide over 68 weeks and 11.1% for orforglipron at the maximum dose.
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Not medical advice. This guide is for general education only. GLP-1 medications, dosing, and treatment suitability are decisions for you and a licensed clinician who knows your full medical history.