CagriSema

CagriSema combines two distinct appetite-suppressing peptide hormones into a single weekly injection, targeting complementary pathways in the brain.

How It Works (Simplified)

Key Research: Garvey WT et al. demonstrated in REDEFINE-1 that CagriSema produced 20.4% mean weight loss at 68 weeks versus 3.0% with placebo in adults with overweight or obesity. PMID:40544433

The cagrilintide-only phase 2 trial (PMID 34798060) is component context, not a CagriSema result. REDEFINE 5 supplies the direct combination-versus-semaglutide obesity comparison; REIMAGINE 2 supplies a separate diabetes comparison.

GRADE meta-analysis in kilograms (not percent)

Khan et al. (PMID:42608559) is a systematic review and GRADE-assessed meta-analysis of 7 randomised trials (n=8,069). Pooled mean difference in weight was −7.58 kg versus semaglutide (95% CI −10.30 to −4.86), −9.24 kg versus cagrilintide (95% CI −10.46 to −8.02), and −13.99 kg versus placebo (95% CI −18.38 to −9.61). Adverse events were primarily gastrointestinal and injection-site reactions, without an increase in serious adverse events. These figures are pooled kilogram differences, not percent weight-loss estimands from a single trial, and they are not converted to percents here.

NDA Submission & REDEFINE Program (2025-2026)

NDA Filing: Novo Nordisk filed a New Drug Application for CagriSema in December 2025, based on the REDEFINE clinical program combining cagrilintide (amylin analog) with semaglutide.

REDEFINE 4 — non-inferiority was missed: The 84-week open-label Phase 3 trial (NCT06131437; n=809) compared CagriSema 2.4 mg/2.4 mg with tirzepatide 15 mg in adults with obesity and a comorbidity. Novo’s February 2026 topline reported 23.0% versus 25.5% weight loss under the on-treatment estimand and 20.2% versus 23.6% under the treatment-regimen estimand. The primary non-inferiority endpoint was not met. This is a sponsor release; detailed peer-reviewed results and ClinicalTrials.gov results tables were not located for this trial in this review.

REDEFINE 5 — published active comparator: In a separate Phase 3 trial in Japan and Taiwan, CagriSema produced an estimated 18.4% mean weight reduction versus 11.9% with semaglutide alone at 68 weeks (estimated difference −6.5 percentage points; 95% CI −8.4 to −4.6; PMID:42009015). This does not reverse REDEFINE 4’s failure against tirzepatide, because the comparator and population differ.

September 2026 sponsor toplines: Novo reported that REIMAGINE 5 found 12.4% weight loss with CagriSema 1.0 mg/1.0 mg versus 9.1% with tirzepatide 5 mg at 60 weeks in adults with type 2 diabetes, while HbA1c lowering was non-inferior. In REDEFINE 9, the same CagriSema strength yielded 21.0% versus 2.0% placebo at 68 weeks in adults with overweight or obesity. These are different doses and study populations from REDEFINE 4 and are sponsor toplines pending detailed publication; they should not be used to claim overall superiority to tirzepatide.

Two registered studies withdrawn: A phase 2 study (NCT07357740) and a phase 3 study (NCT07357766) were both recorded as withdrawn on 9 July 2026. ClinicalTrials.gov gives the same stated reason for each: “The study is withdrawn due to strategic reasons.” Withdrawn means the studies never enrolled a participant, so no data exist from either. The registry does not say what the strategic reasons were.

The REIMAGINE programme — phase 3 in type 2 diabetes (2026)

REDEFINE tested CagriSema for weight management. REIMAGINE is a separate phase 3 programme testing it for glycaemic control in type 2 diabetes, and three of its trials published together on 7 June 2026.

REIMAGINE 1 (PMID:42251860, NCT06323174) randomised 189 adults whose type 2 diabetes was managed on diet and exercise alone, across 42 sites in six countries, to CagriSema at 2.4 mg each, 1.0 mg each, or matched placebo for 40 weeks. From a baseline HbA1c of 7.8%, HbA1c fell 1.8 percentage points at the higher dose and 1.5 at the lower, against 0.1 with placebo. Body weight fell 13.8% at the higher dose against 1.4% with placebo.

REIMAGINE 2 (PMID:42251859, NCT06065540) is the more informative trial, because it is the first phase 3 to put CagriSema against each of its own components. 2,713 adults in 30 countries on metformin, with or without an SGLT2 inhibitor, were randomised across six arms — CagriSema at two dose levels, semaglutide at 2.4 mg and 1.0 mg, cagrilintide 2.4 mg alone, and placebo — for 68 weeks. On the primary comparison, HbA1c fell 1.91 percentage points with CagriSema 2.4 mg/2.4 mg against 1.75 with semaglutide 2.4 mg. The difference of 0.16 percentage points (95% CI 0.05 to 0.27) was statistically significant, and it is a small absolute margin: adding cagrilintide to semaglutide improved glycaemic control, but not by much. Adverse events were reported in 86.9% of the CagriSema group against 81.2% on semaglutide alone. A correction to this paper was published in the same issue.

REIMAGINE 3 (PMID:42251856, NCT06323161) covers an indication this page did not previously mention: CagriSema added to existing basal insulin. 274 adults at 46 centres in six countries, 40 weeks, mean baseline HbA1c 8.8%. HbA1c fell 2.33 percentage points at 2.4 mg each and 2.10 at 1.0 mg each, against 0.66 with placebo. Body-weight reductions were 10 to 12%.

All three trials report their primary endpoint on the efficacy estimand, which analyses on-treatment data and excludes the effect of stopping treatment or starting rescue medication. That is the estimand the papers name as primary, so it is the one quoted here; it is not directly comparable to a treatment-regimen figure from another trial.

Important Limitations

• Not FDA-approved; no application appears in Drugs@FDA as of 6 August 2026. Novo Nordisk reports an NDA submitted in December 2025 and under review
• REDEFINE 4 missed its primary non-inferiority endpoint versus tirzepatide; the available percentages are sponsor-reported and not a peer-reviewed paper
• REIMAGINE 5 and REDEFINE 9 September 2026 toplines likewise await detailed peer review
• The REIMAGINE trials report their primary endpoints on the efficacy estimand only, which describes on-treatment results rather than the effect of being assigned the drug
• Against its own GLP-1 component in REIMAGINE 2, the added glycaemic benefit of cagrilintide was 0.16 HbA1c percentage points
• REDEFINE 4 has an 84-week sponsor-reported readout, but detailed peer-reviewed longer-term safety results were not verified here
• Cardiovascular outcomes trial (REDEFINE-3) still ongoing
• GI side effects occur in approximately 80% of patients (mostly mild-moderate, transient)
• Weight maintenance after discontinuation unknown