Cagrilintide is often compared to GLP-1 drugs, but that comparison needs care: the figures come from different trials, different populations and different treatment durations. Lining up percentages side by side invites wrong conclusions.
Here are the facts first, then what cannot be compared.
[Four compounds, four pathways]
Pramlintide: selective amylin receptor agonist. Approved in 2005 as an insulin adjunct, dosed three times daily. 3.7% placebo-adjusted weight loss at 16 weeks (Aronne et al., 2007, PMID 17504894).
Cagrilintide: dual amylin and calcitonin receptor agonist. Investigational. 10.8% monotherapy weight loss at 26 weeks (4.5 mg, Phase II); 11.5% at 68 weeks (2.4 mg, REDEFINE 1 monotherapy arm). Once weekly (Lau et al., 2021, PMID 34798060; Garvey et al., 2025, PMID 40544433).
Semaglutide: GLP-1 receptor agonist. Approved. 14.9% at 68 weeks (STEP 1) (Wilding et al., 2021, PMID 33567185). Once weekly.
Tirzepatide: GIP + GLP-1 dual agonist. Approved. 20.9% at 72 weeks (SURMOUNT-1) (Jastreboff et al., 2022, PMID 35658024). Once weekly.
Retatrutide: GIP + GLP-1 + glucagon triple agonist. Investigational. 24.2% at 48 weeks (Phase II) (Jastreboff et al., 2023, PMID 37366315). Once weekly.
[The combination picture]
CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg): 20.4% at 68 weeks (REDEFINE 1). That is cagrilintide's best published weight-loss figure.
Note carefully: that figure belongs to the combination, not to cagrilintide alone. Monotherapy sits at 11.5%.
[Two facts worth noting]
First, cagrilintide monotherapy performs like liraglutide, not like tirzepatide. In Phase II, 4.5 mg cagrilintide beat daily 3.0 mg liraglutide by 1.8 percentage points — the only time cagrilintide has beaten an active comparator on the primary endpoint (Lau et al., 2021).
Second, cagrilintide's value is in combination. In REDEFINE 1, semaglutide alone gave 14.9%; adding cagrilintide lifted that to 20.4%, a gain of roughly 5.5 percentage points.
[The trial where CagriSema lost to tirzepatide]
REDEFINE 4: 809 adults with obesity, CagriSema vs tirzepatide 15 mg, open-label, 84 weeks. Result: 23.0% vs 25.5%, failing the non-inferiority endpoint. Announced by Novo Nordisk on 23 February 2026, not yet formally published.
This is the only direct obesity comparison between CagriSema and tirzepatide, and it lost.
[Two new readouts, September 2026]
REIMAGINE 5: adults with type 2 diabetes, CagriSema 1 mg / 1 mg vs tirzepatide 5 mg, 60 weeks. Weight loss 12.4% vs 9.1%.
REDEFINE 9: adults without diabetes, CagriSema 1 mg / 1 mg vs placebo, 68 weeks. 21% vs 2%.
Note both use the lower 1 mg / 1 mg dose, not 2.4 mg / 2.4 mg. Novo Nordisk is exploring lower doses to improve tolerability. Both are company announcements, not yet formally published.
[Why these numbers cannot be compared directly]
First, different populations. REDEFINE 1 excluded people with diabetes; SURMOUNT-1 did too, but enrolment criteria, baseline weight and geography differed.
Second, different durations. Cagrilintide monotherapy data comes from 26 and 68 weeks, tirzepatide from 72 weeks, retatrutide from 48 weeks. Weight-loss curves typically are still declining after 48 weeks, so longer trials produce higher numbers.
Third, different denominators. A higher baseline weight means the same absolute loss registers as a smaller percentage.
Fourth, different placebo responses. Placebo arms ranged from 2% to 3.4% across these trials, which directly affects the net drug effect.
Fifth, unpublished data deserves caution. REDEFINE 4, REIMAGINE 5 and REDEFINE 9 currently exist only as company earnings summaries, not peer-reviewed papers.
[Conclusion]
Monotherapy ranking: retatrutide > tirzepatide > semaglutide > cagrilintide ≈ liraglutide.
Combination: CagriSema at roughly 20.4%, close to tirzepatide monotherapy but still below retatrutide.
Cagrilintide's role is as an adjunct, not a primary agent. On the current data, that positioning is clear.