This is the most complete ranking of these drugs published so far, and reading it as a shopping list produces a strange result: most of the podium is unavailable. It is a map of a menu that is still being written.
What was pooled
Fifty-eight randomized trials covering 24,214 adults, searched across three databases from 2000 to March 2026, all in people with overweight or obesity and without diabetes — trials enrolling people with diabetes, or where diabetes status was unclear, were excluded. [1] That exclusion makes the comparison cleanly about weight and means none of it describes a diabetes population.
Against placebo, retatrutide produced the largest reduction at 22.10%, 95% CI −25.60 to −18.60. Tirzepatide came next at 19.28%, 95% CI −20.39 to −18.16, and CagriSema, a combination of cagrilintide and semaglutide, at 17.32%, 95% CI −19.32 to −15.32. The conventional GLP-1 receptor agonists were more modest. Waist circumference and lipid outcomes followed similar patterns.
The trade at the top
Retatrutide produced the most weight loss and, on low-certainty evidence, also had higher rates of stopping treatment. Danuglipron showed the same pattern. Mazdutide was better tolerated.
That is worth registering before anybody concludes the next generation is simply better. A drug that takes off more weight and that more people stop taking has not obviously beaten a gentler one, and the tolerability evidence here is explicitly graded low.
What the authors say about their own ranking
That confidence intervals overlapped for several comparisons, that head-to-head evidence is limited, and that residual uncertainty should be considered when interpreting comparative effects. Their framing is a probabilistic hierarchy rather than an order of merit.
Look at the intervals. Tirzepatide runs −20.39 to −18.16, which is tight. Retatrutide runs −25.60 to −18.60, which is wide and reaches down into tirzepatide’s range. The difference between first and second place is less settled than the order suggests, which is the standing problem with any pooled ordering.
What a reader can use today
Two things. Tirzepatide’s position is solid — second place with the narrowest interval on the board, from the largest body of trials, and it is buyable. That is a stronger practical statement than retatrutide’s first place.
And the modest tier is where most purchasing actually happens. Semaglutide and the older agonists are what this market sells, and their own evidence is the relevant evidence for almost everybody reading. What is available in which molecule and format is a separate question with a concrete answer.