How much weight, and which drug.

For a long time, weight-loss medication meant a number in the single digits. Five percent of body weight was a good result. Eight was a very good one. Then the GLP-1s arrived and reset the scale, and now the numbers come in steps, each new molecule a little higher than the one before it. The differences are real. They are also more subtle than the headline figures suggest.

Here is where each of the major drugs landed in the trial that defined it.

What each number means

Semaglutide set the modern baseline. In STEP 1, the trial that brought it to obesity medicine, patients on the 2.4 milligram dose lost an average of about fifteen percent of their body weight over sixty-eight weeks.¹ Before this, no drug had reliably done that. Fifteen percent is the number every later molecule is measured against.

Tirzepatide raised it. By acting on two receptors instead of one, GLP-1 and GIP, it produced an average loss of around twenty-one percent at the highest dose in SURMOUNT-1.² That is the difference between a dress size and two, and it arrived only a couple of years after semaglutide.

CagriSema takes a different route. It pairs semaglutide with cagrilintide, a long-acting version of a second gut hormone called amylin. In its first large obesity trial, REDEFINE 1, it produced an average loss in the low twenties.³ The amylin arm appears to add something the GLP-1 alone does not.

Retatrutide sits at the top of the current ladder. It acts on three receptors, GLP-1, GIP, and glucagon, and in its Phase 2 trial the highest dose produced an average loss of about twenty-four percent at forty-eight weeks, with the curve still pointing downward.⁴ Its Phase 3 program is ongoing. The final number may be higher still.

Why this is not a head-to-head race

The chart above is the single most misread image in this category, so it is worth being clear about what it does and does not show. These figures come from different trials, run at different times, in different populations, for different durations, against different placebo groups. They are not a tournament bracket. A drug that produced twenty-one percent in one trial might produce more or less than a drug that produced twenty-two percent in another, if the two were ever tested against each other directly.

A small number of true head-to-head trials are now running. Until they read out, the honest way to read the chart is as a set of independent results, each accurate on its own terms, none of them a direct comparison.

The chart is not a tournament bracket. It is a set of independent results, each accurate on its own terms.

What the differences are actually about

For most patients, the choice between these drugs will not come down to a percentage point of weight loss. It will come down to tolerability, cost, insurance coverage, dosing schedule, and the side-effect profile of the specific molecule. A drug that produces a slightly larger average loss but causes more nausea, or costs three times as much, or is not covered, is not the better drug for that patient.

The more important story in the chart is the trajectory. In the space of a few years, the ceiling moved from fifteen percent to twenty-four, and the molecules at the top of the ladder were designed to address the problems of the ones below them. Retatrutide's glucagon arm is partly about preserving lean mass. CagriSema's amylin arm is partly about appetite signaling the GLP-1 misses. The category is not just getting stronger. It is getting more specific.

Editorial content. Not medical advice. The figures above come from separate published trials and are not direct head-to-head comparisons. Individual response varies. Talk to your prescriber before starting or changing any medication.