# What Weight Loss Drugs Are There Besides Ozempic? Six Have Evidence | This GLP

What weight loss drugs are there besides Ozempic? Six have randomized evidence across 56 trials and 60,307 patients | only two exceeded 10% of body weight.

Publisher: This GLP Editorial Team
Canonical: https://thisglp.com/research/what-weight-loss-drugs-are-there-besides-ozempic
Updated: 2026-09-18
Published: 2026-09-17

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Evidence

# What Weight Loss Drugs Are There Besides Ozempic? Six Have Evidence

Six obesity drugs have randomized evidence behind them and storefronts sell two. Across 56 trials and 60,307 patients, all six beat placebo, and only semaglutide and tirzepatide passed 10%. The cheapest respectable option reaches about eight.

[This GLP Editorial Team](https://thisglp.com/about)September 20269 min read

56 trials, 60,307 patients, six drugs · orlistat · 22 · semaglutide · 14 · liraglutide · 11 · tirzepatide · 6 · naltrexone/bupropion · 5 · phentermine/topiramate · 2 · ⛔ Trial count is not effect size. The order nearly inverts.

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Six obesity drugs have randomized evidence behind them. Storefronts sell two. Across 56 trials and 60,307 patients, all six beat placebo on weight loss, and only semaglutide and tirzepatide exceeded 10% [\[1\]](https://thisglp.com/research/what-weight-loss-drugs-are-there-besides-ozempic#ref-1). The other four are orlistat, liraglutide, naltrexone with bupropion, and phentermine with topiramate. A larger network meta-analysis of 262 trials and 99,791 participants puts phentermine-topiramate at −8.1% against lifestyle alone [\[2\]](https://thisglp.com/research/what-weight-loss-drugs-are-there-besides-ozempic#ref-2).

## Key takeaways

-   A systematic review pooled 56 trials of six obesity medications, enrolling 60,307 patients — 32,598 on a drug and 27,709 on placebo.
-   Every one of the six beat placebo on total body weight loss. Only semaglutide and tirzepatide exceeded 10%.
-   ⛔ Trial counts run almost opposite to effect sizes: orlistat has 22 trials and the smallest effect, tirzepatide 6 and the largest.
-   A 262-trial network meta-analysis puts phentermine-topiramate at -8.1% at one year, against tirzepatide at -14.9%.
-   The older drugs carry their own adverse-event records: orlistat raises serious adverse events at RR 1.45 in hypertensive patients.

The drugs this site tracks are two of six with randomized evidence behind them, and the other four are almost never mentioned on a storefront. This review places all six in one frame. That is the only honest way to answer whether the expensive option is the right one. The trial-by-trial reading in [what the semaglutide trials are worth](https://thisglp.com/research/semaglutide-cochrane-review) can only half answer it.

## What was pooled

A search to 31 January 2025 identified 56 randomized trials comparing obesity medications against placebo or an active comparator, enrolling 60,307 patients [\[1\]](https://thisglp.com/research/what-weight-loss-drugs-are-there-besides-ozempic#ref-1). Orlistat appeared in 22 trials, semaglutide in 14, liraglutide in 11, tirzepatide in 6, naltrexone with bupropion in 5, and phentermine with topiramate in 2. All six produced significantly greater total body weight loss than placebo. Only semaglutide and tirzepatide exceeded 10%.

Trial count is not certainty

The two lists run in nearly opposite orders. Orlistat has the most trials and the smallest effect; tirzepatide has among the fewest and the largest. A reader treating the number of studies as a measure of how sure we are will get this backwards. What the trial count measures is how long a drug has existed and how hard anyone bothered to study it.

## The ranking, from the largest comparison

The biggest synthesis so far pooled 262 randomized trials and 99,791 participants across 19 drugs [\[2\]](https://thisglp.com/research/what-weight-loss-drugs-are-there-besides-ozempic#ref-2). At one year against lifestyle modification alone, tirzepatide led at −14.9%, 95% CI −16.0% to −13.9%. Cagrilintide-semaglutide came next at −14.8%, oral semaglutide at −10.9%, orforglipron at −9.9%, injected semaglutide at −9.8%, and phentermine-topiramate at −8.1%. All of those carry moderate to high certainty.

So the cheapest drug with a respectable result is phentermine with topiramate, at a little over half what tirzepatide achieves. Taking phentermine alongside semaglutide is a separate question, and [no trial has tested that pairing](https://thisglp.com/research/can-you-take-phentermine-with-ozempic). That is the trade a reader is actually being asked to make, and it is never framed that way on a storefront. The tolerability side of the same analysis is in [the discontinuation ranking](https://thisglp.com/research/the-best-losers-are-the-worst-tolerated).

## What the older drugs cost in side effects

A Cochrane review of long-term weight drugs in people with hypertension reports the harms in a way the efficacy reviews do not [\[3\]](https://thisglp.com/research/what-weight-loss-drugs-are-there-besides-ozempic#ref-3). Orlistat probably increases serious adverse events at RR 1.45, 95% CI 1.10 to 1.91, across three trials and 1,476 participants. Naltrexone with bupropion probably increases all adverse events at RR 1.69, 95% CI 1.58 to 1.80. Phentermine with topiramate probably increases them at RR 1.13, 95% CI 1.08 to 1.20.

None of that makes the older drugs unusable. It means the cheaper option is cheaper partly because it is older and partly because it does less, and its side-effect record is not blank. The same review found the semaglutide and tirzepatide trials reported no adverse-event results at all in that population, which is a different problem, set out in [the Cochrane update](https://thisglp.com/research/eight-trials-and-nobody-counted-the-deaths).

## What none of this establishes

Which drug is better than which, for a particular person. Fifty-six trials with different populations, durations and comparators can establish that each beats placebo. They cannot substitute for putting two drugs in one protocol. The review’s own conclusion is that the choice should be individualized rather than ranked, and the one head-to-head that does exist is read in [the tirzepatide against semaglutide comparison](https://thisglp.com/research/tirzepatide-vs-semaglutide-which-works-better).

The drugs still in trials are a separate category again. Ecnoglutide, mazdutide and retatrutide may produce reductions of 13.1% to 14.6%, with certainty graded very low to low, and none of them can be bought. What is coming and what is buyable are separated in [the pipeline reading](https://thisglp.com/research/what-new-weight-loss-drugs-are-coming).

## Why the other four matter to a buyer

Because they are cheaper, and because nobody selling a GLP-1 will mention them. Four drugs with randomized evidence of real weight loss exist outside this market entirely, at a fraction of what this roster charges. They have smaller effects and their own side-effect profiles.

That does not make them the right choice. The effect sizes really are smaller, and for many people the difference between 5% and 15% is the difference between a result and none. It does mean a reader comparing only the two drugs a storefront sells is comparing a shortlist somebody else wrote.

## Frequently asked

What weight loss drugs are there besides Ozempic?

Five others carry randomized evidence: tirzepatide, liraglutide, orlistat, naltrexone with bupropion, and phentermine with topiramate. All six beat placebo, and only semaglutide and tirzepatide exceeded 10% of body weight.

Which is the cheapest drug that actually works?

Phentermine with topiramate reached −8.1% at one year against lifestyle modification alone, in a network meta-analysis of 262 trials, against tirzepatide at −14.9%.

Do the older drugs have worse side effects?

They have their own records. Orlistat probably increases serious adverse events at RR 1.45, and naltrexone with bupropion increases all adverse events at RR 1.69, both in hypertensive populations.

Does more trials mean more certainty?

Not here. Orlistat has 22 trials and the smallest effect; tirzepatide has 6 and the largest. Trial count measures how long a drug has existed, not how well it works.

## Sources

1.  \[1\] McGowan B, et al. (2025). A systematic review and meta-analysis of the efficacy and safety of pharmacological treatments for obesity in adults Nature Medicine. [PMID 41039116](https://pubmed.ncbi.nlm.nih.gov/41039116/)
2.  \[2\] Nong K, Shi Q, Xie X, Wang Y, Agarwal A, Guyatt GH, et al. (2026). Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis BMJ. [PMID 42419792](https://pubmed.ncbi.nlm.nih.gov/42419792/)
3.  \[3\] Spary-Kainz U, Posch N, Radl-Karimi C, Jeitler K, Krenn C, Siebenhofer A (2026). Long-term effects of weight-reducing drugs in people with hypertension Cochrane Database of Systematic Reviews. [PMID 42318855](https://pubmed.ncbi.nlm.nih.gov/42318855/)

## Where to get it

### Best GLP-1 injections

Every injectable seller we can verify, with the price each one publishes and an honest read of what the trials measured.

[Compare providers →](https://thisglp.com/best/compounded-semaglutide)

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