# Is CagriSema Better Than Semaglutide Alone? By 6.5 Points, Head to Head A 331-person randomized trial found cagrilintide-semaglutide cut weight 18.4% against 11.9% for semaglutide alone, with adverse events of 87% vs 84%. Publisher: This GLP Editorial Team Canonical: https://thisglp.com/research/is-cagrisema-better-than-semaglutide Updated: 2026-09-17 Published: 2026-09-17 [← Research](https://thisglp.com/research) Evidence # Is CagriSema Better Than Semaglutide Alone? By 6.5 Points, Head to Head The trial built to answer it gave both arms 2.4 mg and found 18.4% against 11.9%. Against placebo the combination looks twice as impressive, which is the point. [This GLP Editorial Team](https://thisglp.com/about)September 20267 min read Weight change at week 68 · CagriSema, head-to-head · −18.4% · semaglutide alone, same trial · −11.9% · CagriSema, REDEFINE 1 · −20.4% · The gap between the top two is the answer: 6.5 points. **Research, not medical advice.** This GLP is independent and educational. Nothing here is a substitute for individualized care from a licensed clinician, and reading it creates no doctor–patient relationship. Talk to your own provider before starting, stopping, or changing any medication, peptide, or therapy. See our [methodology](https://thisglp.com/methodology) and [terms](https://thisglp.com/terms). ## Key takeaways - A randomized trial in 331 adults in east Asia gave both arms 2.4 mg and compared the combination directly against semaglutide alone. - Weight fell 18.4% on the combination against 11.9% on semaglutide alone — a difference of 6.5 percentage points (95% CI -8.4 to -4.6). - Adverse events were 87% against 84%, so the extra weight loss did not cost measurably more side effects. - REDEFINE 1, the larger placebo-controlled trial, reached 20.4% against 3.0% on placebo in 3,417 people. 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 [\[1\]](https://thisglp.com/research/is-cagrisema-better-than-semaglutide#ref-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](https://thisglp.com/research/is-tirzepatide-better-than-dulaglutide). The extra weight loss did not cost extra side effects Adverse events occurred in 87% of the combination group against 84% on semaglutide alone, and gastrointestinal events in 53% against 51%. Discontinuation ran 10% against 6%. Adding a second agent for 6.5 more points without a clear tolerability penalty is the commercially important part of this trial, and the part most in need of replication — it is the opposite of the trade in [the network meta-analysis of nineteen drugs](https://thisglp.com/research/the-best-losers-are-the-worst-tolerated). Adding phentermine to a GLP-1 drug has been tested only with liraglutide, in [one 12-week trial](https://thisglp.com/research/can-you-take-phentermine-with-ozempic). ## 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 [\[2\]](https://thisglp.com/research/is-cagrisema-better-than-semaglutide#ref-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 The same combination, measured against two different things. | 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) | The same combination, measured against two different things. REDEFINE 1 and the 2026 head-to-head trial 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](https://thisglp.com/research/tirzepatide-vs-real-clinical-practice): 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](https://thisglp.com/research/glp1-weight-loss-pooled-average). 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](https://thisglp.com/research/does-semaglutide-help-liver-cirrhosis), every combination failed and the single agent won. ## Frequently asked Is CagriSema better than semaglutide on its own? In the trial built to compare them, yes — 18.4% against 11.9% over 68 weeks with both arms at 2.4 mg, a difference of 6.5 percentage points. Why do some figures say 20% and others 18%? Different comparators. REDEFINE 1 reported 20.4% against placebo in 3,417 people; the head-to-head reported 18.4% against semaglutide alone in 331 people. Against nothing, the combination looks far larger. Does the combination cause more side effects? Not measurably in the head-to-head: adverse events were 87% against 84% and gastrointestinal events 53% against 51%, though discontinuation was 10% against 6%. Do the weight figures apply everywhere? The 6.5-point gap should travel; the absolute numbers may not. Participants were from east Asia and the semaglutide arm reached 11.9%, below what Western trials report at the same dose. ## Sources 1. \[1\] Yamauchi T, Becker NP, Hagemann CA, Huang KC, Kiyosue A, Lim S (2026). Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity The Lancet Diabetes & Endocrinology. [PMID 42009015](https://pubmed.ncbi.nlm.nih.gov/42009015/) 2. \[2\] Garvey WT, Blüher M, Osorto Contreras CK, Davies MJ, Winning Lehmann E, Pietiläinen KH (2025). Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity The New England Journal of Medicine. [PMID 40544433](https://pubmed.ncbi.nlm.nih.gov/40544433/) ## 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) ## More in Evidence - [ 150 minutes · Weekly activity goal · 2 days · Muscle strengthening · Adapt · Symptoms and ability ### Exercise on Ozempic: Building Strength Without Ignoring Symptoms ](https://thisglp.com/research/exercise-on-ozempic) - [ STEP 1, semaglutide 2.4 mg vs placebo, % change at 68 weeks · LDL cholesterol · −2.5% vs +1.3% · Total cholesterol · −3.3% vs +0.1% · HDL cholesterol · +5.2% vs +1.4% · Triglycerides · −21.9% vs −7.3% · Wegovy label, Table 13. Adults without diabetes. Ozempic doses are lower. ### Does Ozempic Lower Cholesterol? 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