AMYLIN ANALOG + GLP-1 RECEPTOR AGONIST

CagriSema

A fixed-dose cagrilintide/semaglutide combination with substantial Phase 3 weight-loss efficacy—and a useful lesson in why headline percentages need comparator context.

M4 Evidence Maturity · Advanced Clinical

Investigational · Phase 3

Evidence reviewed: September 19, 2026Sponsor-reported + registered trials

Signal summary

CagriSema combines two appetite-regulating pathways: cagrilintide, an amylin analog, and semaglutide, a GLP-1 receptor agonist.

Signal interpretation: CagriSema has a strong weight-loss signal, but the 2026 REDEFINE 4 head-to-head result also shows why RecompSignal tracks trial design and comparator performance instead of treating every large percentage as a win.

Study details

Doses studied — not a dosing recommendation. Regimens belong to the named study, formulation and population.

REDEFINE 4 phase 3 head-to-head trial

Population: 809 adults with obesity and one or more comorbidities; open-label trial.
Doses and administration studied: Cagrilintide 2.4 mg plus semaglutide 2.4 mg versus tirzepatide 15 mg; both subcutaneously once weekly.
Duration: 84 weeks
Reported finding / status: Sponsor efficacy-estimand weight loss: 23.0% vs 25.5%; treatment-regimen estimates: 20.2% vs 23.6%. CagriSema did not demonstrate noninferiority.
Interpretation and limitations: These are two different estimands, not interchangeable results. The comparison does not establish superior lean-mass preservation.

Source tier E · Read the original study or record

Outcome Evidence Strength

Weight change2/5

Fat-mass change0/5

Lean-mass change0/5

Strength / function benefit0/5

This card’s head-to-head result is sponsor-reported. Fat, lean and functional superiority are not established by that report.

Editorial evidence ratings for the cited outcomes, not effect size or treatment recommendations. A lean-mass score may describe loss. 0 means not established in the reviewed evidence, not proof of no effect. Read the rubric.

What is actually established?

Novo Nordisk reported 23.0% weight loss at 84 weeks under an efficacy estimand in REDEFINE 4.
The trial did not meet its primary endpoint of non-inferiority versus tirzepatide 15 mg.
Additional Phase 3 studies, including higher-dose CagriSema, are ongoing.

What is not established?

CagriSema remains investigational.
Strong scale-weight reduction does not establish superior lean-mass preservation.
The head-to-head result should not be reduced to a single percentage without noting the estimand and comparator.

Still being studied

Full peer-reviewed head-to-head results, higher-dose development and composition-specific outcomes.

Best human evidence at a glance

Evidence	Population	Comparator & duration	Outcome measured	Evidence state
REDEFINE 4	809 adults with obesity and at least one comorbidity	Open-label; active comparator: tirzepatide 15 mg · 84 weeks	Scale-weight efficacy under prespecified estimands	Sponsor-reported Full peer-reviewed detail is needed for deeper interpretation.
High-dose CagriSema study	Registered Phase 3 obesity population	Active comparator: semaglutide	Weight and prespecified clinical outcomes	Registered trial Outcome evidence is pending.

Measurement context: Headline weight-loss percentages should be read with the estimand, comparator and analysis population. They do not independently establish fat selectivity, lean-mass preservation or function.

Safety evidence context

Safety and tolerability evidence remains part of an investigational development program. Full peer-reviewed and regulatory review may change the interpretation.

Interpretation boundary

This card tracks research and does not recommend investigational use, dosing or sourcing.

Sep 11, 2026

What changed: Added explicit sponsor-versus-registry labeling, comparator context and separate maturity and outcome definitions.

Evidence sources

A = regulatory/official • B = peer-reviewed randomized/meta-analysis • C = peer-reviewed review/observational • D = registered trial • E = sponsor-reported • F = preclinical

Source tier E — Sponsor-reported Phase 3
REDEFINE 4 headline results, February 2026

Source tier D — Registered Phase 3
High-dose CagriSema vs semaglutide study

Last evidence review: September 19, 2026.

Educational use only. This page summarizes research evidence and regulatory status. Study doses describe research, not prescribing instructions. This page does not provide personalized dosing, self-use protocols, sourcing, or a recommendation to use this therapy.