GLP-1s vs. Phentermine, Qsymia, and Contrave: Results, Cost, Risks

GLP-1 medications produce clearly more weight loss than the older drugs. In a 2025 network meta-analysis, tirzepatide and semaglutide beat placebo by about 16% and 12% of body weight, compared with about 9% for Qsymia and 5% for Contrave. The older drugs still win on price, and that is the real trade-off this comparison comes down to.

The short answer: effect size vs. price

If the question is "which drug is most likely to move the scale the most," the answer is a GLP-1 class drug, and tirzepatide in particular. A 2025 systematic review and network meta-analysis in Nature Medicine pooled 56 randomized trials with more than 60,000 participants. Placebo-subtracted weight loss was 16.2% for tirzepatide, 11.9% for semaglutide, 8.8% for phentermine/topiramate, and 4.8% for naltrexone/bupropion.

If the question is "what can I afford for a year or more," the picture shifts. The older drugs are mostly generic or have aggressive manufacturer cash programs. That gap matters because weight-loss drugs tend to work only while you keep taking them.

Side-by-side comparison

Source: McGowan et al., Nature Medicine 2025; FDA labels for Qsymia, Contrave, and Wegovy; pricing from GoodRx, Fierce Pharma, Lilly, and Close Concerns. Prices change often; confirm before filling.

Results: what the trials actually showed

GLP-1s

In the STEP 1 trial, people on semaglutide 2.4 mg lost an average of 14.9% of body weight at 68 weeks, compared with 2.4% on placebo, according to the American College of Cardiology trial summary. In SURMOUNT-1, tirzepatide 15 mg produced 20.9% weight loss at 72 weeks versus 3.1% on placebo (ACC summary). Those are single-trial numbers, which run higher than the placebo-subtracted pooled estimates above.

Qsymia

In the 56-week CONQUER trial, people lost an average of 10.2 kg on the higher dose and 8.1 kg on the lower dose, versus 1.4 kg on placebo, as summarized by NEJM CardioExchange. Seventy percent of high-dose patients reached at least 5% weight loss. That makes Qsymia the closest older competitor to semaglutide.

Contrave

The Contrave label reports 5.4% average weight loss versus 1.3% on placebo in its main 56-week trial (COR-I). When paired with an intensive behavior program (COR-BMOD), the figure was 8.1% versus 4.9%. In the trial of people with type 2 diabetes it was 3.7% versus 1.7%.

Phentermine alone

Phentermine is the most prescribed older drug, but its FDA label describes it as "a short-term (a few weeks) adjunct" to diet and exercise. It was not part of the 2025 pooled analysis, so there is no apples-to-apples long-term number to put next to a GLP-1. Some clinicians prescribe it longer off-label; that is a decision for your prescriber, not something the label supports.

Cost: where the older drugs pull ahead

Price is the strongest argument for the older drugs. As of October 2026:

• Phentermine: GoodRx lists about $17 for 30 capsules of 37.5 mg, against average retail prices of roughly $38 to $43 (GoodRx).
• Qsymia: A generic launched in May 2025. GoodRx shows about $59 for generic and $176 for brand at the 7.5/46 mg dose. The manufacturer's Qsymia Engage home-delivery program can bring a 90-day brand supply to as little as $70 (GoodRx).
• Contrave: The average retail price is about $757 a month, but the manufacturer's program offers it for "$99 or less per month" (GoodRx).
• Wegovy: $349 a month for the injection at any dose; the Wegovy pill launched at $149 for the starting dose and $299 for the highest doses (Fierce Pharma).
• Zepbound: $299 for the starting dose and as low as $449 for maintenance doses with Lilly's self-pay card, which runs through December 31, 2026 (Lilly).

Medicare changes this math for some people. Since July 1, 2026, the Medicare GLP-1 Bridge covers Wegovy, Foundayo, and the Zepbound KwikPen for $50 a month for eligible beneficiaries. The older drugs are not part of that program.

Side effects and who should avoid each

The safety profiles are different enough that one class may be ruled out for you before cost even comes up.

• Phentermine is a stimulant. Its label lists palpitations, rapid heart rate, raised blood pressure, insomnia, and dry mouth, and it is contraindicated in people with heart disease, uncontrolled hypertension, hyperthyroidism, glaucoma, or a history of drug misuse.
• Qsymia can cause fetal harm. The label recommends a negative pregnancy test before starting and monthly during treatment, and under its REMS program only certified pharmacies may dispense it. Tingling (14% to 20% at the 7.5/46 mg and 15/92 mg doses) and dry mouth (14% to 19%) were among the most common complaints.
• Contrave carries a boxed warning about suicidal thoughts because it contains bupropion. It cannot be used with chronic opioids, and it can raise blood pressure. Nausea affected 32.5% of users in trials.
• GLP-1s mainly cause GI effects. On the Wegovy label, nausea hit 44% of users (16% on placebo) and vomiting 24%. They carry a boxed warning about thyroid C-cell tumors seen in rodents and are not used in people with a personal or family history of medullary thyroid cancer or MEN 2.

Built-in "is it working?" checkpoints

Both older combination drugs come with explicit stopping rules, which helps you avoid paying for a drug that is not working:

• Contrave: If you have not lost at least 5% of body weight after 12 weeks at the maintenance dose, the label says to discontinue.
• Qsymia: If weight loss is under 3% after 12 weeks on the standard dose, the label allows escalation; if it is under 5% after 12 weeks on the top dose, discontinue.

That structure makes a 3-month trial of an older drug a defined, low-cost experiment. If it fails, moving to a GLP-1 is a reasonable next conversation with your prescriber.

When an older drug can be the better fit

• Cost is the deciding factor and you have no GLP-1 coverage. Generic phentermine/topiramate gives you roughly three-quarters of semaglutide's pooled effect at a fraction of the price.
• You cannot take a GLP-1, for example because of a personal or family history of medullary thyroid cancer, or because GI side effects were intolerable.
• You want a short-term start and your prescriber thinks a few weeks of phentermine fits your plan, knowing that is what its label covers.

When a GLP-1 is usually the better fit:

• You need 15% or more weight loss for a health goal, such as improving sleep apnea or qualifying for another procedure.
• You have heart disease or uncontrolled blood pressure, which rules out phentermine and makes Contrave harder to use.
• You could become pregnant and want to avoid Qsymia's birth-defect risk and the monthly pregnancy testing its label recommends.
• You qualify for Medicare's $50 Bridge or have commercial coverage for GLP-1s.

Sources

1. McGowan et al. Obesity medications network meta-analysis, Nature Medicine (2025)
2. Qsymia prescribing information, FDA (2026)
3. Contrave prescribing information, FDA (2025)
4. Wegovy prescribing information, FDA (2025)
5. Adipex-P (phentermine) prescribing information, Drugs.com
6. STEP 1 trial summary, American College of Cardiology
7. SURMOUNT-1 trial summary, American College of Cardiology
8. Phentermine-topiramate combination yields significant weight loss (CONQUER), NEJM CardioExchange
9. Phentermine prices, GoodRx
10. Qsymia cost, GoodRx
11. How to save on Contrave, GoodRx
12. Wegovy pill launches at $149 per month, Fierce Pharma
13. Zepbound coverage and savings, Eli Lilly
14. Foundayo (orforglipron) receives FDA approval, Close Concerns
15. Medicare GLP-1 Bridge: GLP-1 drugs for $50 a month, Medicare.gov

Medical disclaimer: This article is general information, not medical advice, and does not replace a licensed clinician who knows your history. Approvals, labels, coverage and prices change; check the linked sources and talk with your prescriber or pharmacist before making decisions about any medication.