Yes, by about 6.5 percentage points, in the one trial built to answer it directly. The useful part is how small that margin is beside the headline figures, and what it cost in tolerability.
The trial that compared them head to head
A randomized, masked trial gave 331 adults in east Asia either cagrilintide-semaglutide or semaglutide alone, both escalated to 2.4 mg, for 68 weeks [1]. Weight fell 18.4% on the combination and 11.9% on semaglutide alone. The estimated treatment difference was 6.5 percentage points, with an interval from 8.4 to 4.6.
Both arms reached the same dose, so this is not the mismatched-dose comparison this site keeps finding elsewhere — the problem set out in the tirzepatide network comparison.
A correction to what this site previously said
This site has twice described the head-to-head comparison as missing from the CagriSema program. That was not accurate, and the record is worth correcting.
REDEFINE 1 randomized 3,417 participants in a 21:3:3:7 ratio: 2,108 to the combination, 302 to semaglutide alone, 302 to cagrilintide alone and 705 to placebo [2]. A semaglutide-alone arm was there from the start.
What was true is narrower. REDEFINE 1’s co-primary endpoints were both stated against placebo. The comparison against semaglutide alone therefore sat in the trial as a secondary question, not the one it was powered to answer. The 2026 trial made that comparison its primary purpose.
What REDEFINE 1 found
| Trial | Compared against | Result |
|---|---|---|
| REDEFINE 1, n=3,417 | Placebo | −20.4% vs −3.0%, difference −17.3 (95% CI −18.1 to −16.6) |
| Head-to-head, n=331 | Semaglutide 2.4 mg alone | −18.4% vs −11.9%, difference −6.5 (95% CI −8.4 to −4.6) |
Gastrointestinal adverse events affected about 79% of the combination group in REDEFINE 1. Its analysis used a treatment-policy estimand, consistent with intention to treat, which counts what happened to everyone randomized rather than only those who stayed on the drug.
Read the two rows together and the shape is clear. Against nothing, the combination looks enormous. Against the drug you would otherwise take, it is worth about 6.5 points. That is the same lesson as the ladder of comparators: the harder the comparator, the smaller the claim.
What does not transfer
The head-to-head enrolled participants from east Asia and the authors frame their conclusion that way. Its semaglutide-alone arm reached 11.9%, noticeably below the figures Western trials report for the same dose in the pooled weight-loss averages.
So the 6.5-point gap is the trial’s finding and should travel. The 18.4% is not a number to promise anyone elsewhere. The trial was also 68% male, unusual for an obesity trial, and funded by Novo Nordisk, which the paper states.
Whether stacking a second agent helps at all appears to depend entirely on which second agent. In the zalfermin trial, every combination failed and the single agent won.