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, which is the only honest way to answer whether the expensive option is the right one — a question the trial-by-trial reading in what the semaglutide trials are worth can only half answer.
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]: orlistat 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%.
Where the two diverge
Both semaglutide and tirzepatide showed restoration of normoglycemia, remission of type 2 diabetes, and a reduction in hospitalization for heart failure. Beyond that their records differ, and the difference is not a matter of degree.
Semaglutide was effective in reducing major adverse cardiovascular events and in reducing pain in knee osteoarthritis. Tirzepatide was effective in remission of obstructive sleep apnea and of metabolic dysfunction-associated steatohepatitis. Neither carries the other’s results, and writing “these drugs” across both would erase a real distinction — the same one at issue in tirzepatide against semaglutide.
What the review does not establish
Which drug is better than which. Fifty-six trials with different populations, durations and comparators can establish that each beats placebo and cannot substitute for putting two drugs in one protocol. The authors’ own conclusion is that the choice should be individualized rather than ranked.
That is the same limit as the one in what a comparator can and cannot tell you, arriving from the other direction: there, a comparison could not speak about one arm alone; here, separate comparisons cannot be chained into a ranking.
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, with 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, and the question of whether the premium is worth paying is in what the semaglutide trials are worth.