Medications
Phentermine vs Ozempic, and the Older Drugs Nobody Mentions
The comparison articles on this subject almost all stop at two drugs, and both of the drugs they pick are the expensive one and the old one. There are four other approved medications sitting between them, and for a large number of patients one of those is the right answer.
What follows is the whole set, with the trial numbers, so you can see where each one actually lands.
The numbers, in one place
Average weight loss at roughly one year, from the pivotal trials:
| Medication | Average weight loss | Trial |
|---|---|---|
| Phentermine alone | About 5 to 10 percent over 3 to 6 months | No modern long term trial |
| Contrave, naltrexone and bupropion | 6.1 percent vs 1.3 percent placebo at 56 weeks | COR-I |
| Qsymia, phentermine and topiramate, top dose | 10.9 percent vs 1.6 percent placebo at 56 weeks | EQUIP, severe obesity, mean BMI about 42 |
| Qsymia, top dose | 9.8 percent vs 1.2 percent placebo at 56 weeks | CONQUER, BMI 27 to 45 with two or more comorbidities |
| Foundayo, oral orforglipron, top dose | 12.4 percent vs 0.9 percent placebo | ATTAIN-1 |
| Semaglutide 2.4 mg | About 15 percent at 68 weeks | STEP 1 |
A few things fall out of that table immediately.
Phentermine on its own is the only entry without a modern long term trial behind it, which is a consequence of when it was approved rather than a judgment about whether it works.
Qsymia at the top dose gets within a few percentage points of the injectable GLP-1s, and it is a pill that has been available since 2012.
And the gap between Contrave and semaglutide is real but smaller than the price difference between them would suggest.
Phentermine, approved in 1959
Phentermine received FDA approval in 1959. It has been in continuous use for treating obesity for longer than any other drug on this list, longer than most of the physicians prescribing it have been alive.
It is a Schedule IV controlled substance, and its label describes it as a “short term (a few weeks) adjunct in a regimen of weight reduction.” That label language is the source of most of the confusion around it. It reflects the regulatory environment of 1959 and the trials that existed then, not a current judgment that the drug stops working or becomes unsafe after twelve weeks. In practice, clinicians prescribe it for longer than the label describes, with monitoring, and the professional literature has been arguing for a label update for years.
What it does is suppress appetite through the sympathetic nervous system. What it does not do is anything metabolic. It does not improve insulin sensitivity, it does not affect cardiovascular outcomes, and it does not do anything for you after you stop taking it.
It is also, by a wide margin, the least expensive option in this article. It is generic, it is on essentially every pharmacy discount program, and a month of it costs a small fraction of what a single week of a branded GLP-1 costs.
Qsymia, and why the combination exists
Qsymia was approved in July 2012. It combines phentermine with topiramate.
Topiramate is an anticonvulsant, approved for epilepsy and later for migraine prevention. Weight loss was an unwanted effect that turned up in the seizure trials, consistent enough that it was eventually studied on purpose. Combining it with phentermine allows both to be dosed lower than either would be alone while producing more weight loss than either produces alone.
The results are the strongest of any oral option that predates the GLP-1 pills. In EQUIP, the top dose produced 10.9 percent weight loss against 1.6 percent on placebo at 56 weeks. In CONQUER, which enrolled 2,487 patients, the top dose produced 9.8 percent against 1.2 percent, and 70 percent of patients on it lost at least 5 percent of their body weight compared with 21 percent on placebo.
The limiting factors are real. Topiramate causes cognitive slowing and word finding difficulty in some patients, it causes tingling in the hands and feet, and it is teratogenic, which requires pregnancy testing and reliable contraception for anyone who could become pregnant.
Your history narrows the list faster than any ranking does
Your blood pressure, your sleep, what you have already tried and what your plan covers narrow the list quickly.
Contrave, and the two drugs inside it
Contrave was approved in September 2014. It combines naltrexone and bupropion.
Naltrexone is an opioid receptor antagonist, developed and approved for opioid and alcohol dependence. Bupropion is an antidepressant, marketed separately for depression and, under a different name, for smoking cessation. Neither was designed to treat obesity.
The combination works on the reward side of eating rather than on hunger. Bupropion increases activity in the hypothalamic pathway that reduces appetite, and naltrexone blocks a feedback loop that would otherwise blunt that effect. The practical result patients describe is not that they feel full sooner, but that food they used to think about constantly stops occupying the same amount of mental space.
In COR-I, the 32 mg naltrexone dose produced 6.1 percent weight loss at 56 weeks against 1.3 percent on placebo. The 16 mg dose produced 5.0 percent. Both were significant against placebo.
For a specific kind of patient, the one who describes food noise rather than physical hunger, this is often the better drug even though its average result is lower.
Every one of these was a side effect first
Naltrexone was built for addiction. Bupropion was built for depression. Topiramate was built for seizures. Metformin came out of a plant used for centuries before anyone isolated why it worked.
The pattern is not an accident, and it is not a knock on the drugs. Obesity pharmacology spent forty years advancing mostly by noticing that a drug developed for something else was making people lose weight, and then studying that effect properly. The GLP-1s are the first class in a long time that was aimed at this problem from the start.
That history is why the older drugs are cheap. They are generic, or built from generics, and the development cost was paid off by a different indication decades ago.
The combinations matter as much as the single drugs
Several of these medications work better paired than alone, and the pairing depends on which side effects you can live with.
Metformin’s actual role
Metformin is not approved for weight loss and should not be described as a weight loss drug. It produces modest weight change in most people who take it, generally a few pounds rather than a few dress sizes.
Where it earns a place is in patients who have insulin resistance, prediabetes, or polycystic ovary syndrome, where it is treating the underlying problem and the weight effect is secondary. It is inexpensive, it has decades of safety data, and it combines with almost everything else on this list.
Anyone selling metformin as a primary weight loss treatment is overselling it.
What changed in April 2026
The FDA approved orforglipron, marketed as Foundayo, on April 1, 2026. It is the first GLP-1 in a pill that is not a peptide, which means it does not require the food and water timing restrictions that oral semaglutide does, and it does not require refrigeration or an injection.
In ATTAIN-1, the highest dose produced 12.4 percent weight loss against 0.9 percent on placebo, or 11.1 percent against 2.1 percent when the analysis included everyone randomized regardless of whether they stayed on treatment. It is approved at doses of 0.8, 2.5, 5.5, 9, 14.5, and 17.2 mg.
That result sits above Qsymia and below injectable semaglutide. It is a meaningful addition, and it is not a replacement for the injectables at the top of the range. Anyone describing an oral GLP-1 as equivalent to Wegovy or Zepbound is not reading the trial.
Combining an oral agent with a GLP-1
This comes up constantly, usually from patients who have plateaued on a GLP-1 and do not want to escalate the dose or the cost.
The evidence is thin. A small pilot combining a GLP-1 with phentermine reported only one to two percentage points of additional weight loss, and it is not standard practice. Combining is done in real clinics, under supervision, for specific reasons, most often to hold a result while reducing the GLP-1 dose for cost or tolerability.
What it should not be is a way to self assemble a regimen from three prescriptions written by three different telehealth services that do not know about each other. Phentermine and a GLP-1 both affect heart rate. Bupropion lowers the seizure threshold. These interactions are manageable when one clinician is holding the whole picture and dangerous when nobody is.
Oral agents and GLP-1s are both prescribed here
Karas Weight Loss and Wellness prescribes across both categories, so the answer for you is not limited to whichever drug a clinic happens to focus on.
Worth checking your liver while you are at it
Roughly a quarter to a third of American adults are carrying a fatty liver, and among people with type 2 diabetes the estimates run from 30 to 75 percent. Most of them have no symptoms and normal bloodwork. Losing 3 to 5 percent of your body weight starts moving it.
Who each one is actually for
Phentermine alone suits someone with a modest amount to lose, no cardiovascular risk factors that rule out a stimulant, and a budget that rules out everything else.
Qsymia suits someone who needs a result closer to the GLP-1 range, can tolerate topiramate, and is not planning a pregnancy.
Contrave suits the patient whose problem is preoccupation with food rather than physical hunger, and it pairs naturally with someone already taking bupropion for another reason.
Metformin suits the patient with insulin resistance or PCOS, usually alongside something else.
An oral GLP-1 suits someone who wants GLP-1 level results without an injection and does not need the highest end of the range.
An injectable GLP-1 suits someone who needs the largest medical result available, and who can either afford it or has coverage for it.
And surgery remains the option with the largest and most durable effect for people whose BMI and history put them in range for it, which is a separate conversation rather than a competing one. Many patients use medication first, then surgery, or surgery first and medication later for maintenance.
Common questions
Is phentermine as good as Ozempic? No. Phentermine produces roughly 5 to 10 percent weight loss over a few months and has no metabolic effect. Semaglutide produced about 15 percent at 68 weeks in STEP 1 and treats the underlying disease. Phentermine costs a tiny fraction of what a branded GLP-1 costs, which is why it is still the right answer for some patients.
Can I take phentermine long term? The label describes a few weeks. Clinicians commonly prescribe it longer with monitoring, and the professional literature supports doing so in appropriate patients. That is a decision to make with a prescriber who is checking your blood pressure and heart rate, not one to make on your own.
Is Contrave better than Ozempic? Not on average weight loss. It produced 6.1 percent against semaglutide’s roughly 15 percent. For a patient whose main problem is intrusive thoughts about food, the mechanism can suit them better even though the average number is lower.
What is the cheapest weight loss medication that actually works? Phentermine, which is generic and available on every pharmacy discount program, is the least expensive option with real evidence behind it. Metformin is comparably inexpensive but is not a weight loss drug. Both cost a small fraction of a branded GLP-1.
Do these work after you stop taking them? No, and neither do the GLP-1s. Every medication on this list treats obesity while you are taking it. That is the honest limitation of the entire category and the reason maintenance planning matters more than the drug you start with.
Can I take phentermine with a GLP-1? It is done under supervision in some cases. The evidence for added benefit is limited, both raise heart rate, and it should never be assembled from separate prescribers who are unaware of each other.
Find the right one for you
Six approved medications, and the right one depends on how you actually experience hunger, what else you take, what your heart and blood pressure will tolerate, and what you can afford month after month. Sorting that out takes one appointment.
Sources
Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010;376(9741):595-605. Results also posted at ClinicalTrials.gov NCT00532779.
Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity. 2012;20(2):330-342.
Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER). Lancet. 2011;377(9774):1341-1352.
U.S. Food and Drug Administration. FDA Approves First New Molecular Entity Under National Priority Voucher Program. April 1, 2026.
Eli Lilly and Company. FDA Approves Lilly’s Foundayo (orforglipron). April 1, 2026.
U.S. Food and Drug Administration. ADIPEX-P (phentermine hydrochloride) prescribing information.
Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002.