CagriSema versus semaglutide 2.4 mg: meta-analysis of five trials, 4,746 adults, reports greater weight loss
A systematic review and meta-analysis of five randomised trials in 4,746 adults reports a 6.89 percentage-point greater weight reduction with CagriSema than semaglutide 2.4 mg, with more frequent injection-site reactions.
Frontiers in endocrinology · 2026 · Meta-analysis · n=4746 · Human · Published October 20, 2026
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What the review did
This was a systematic review and meta-analysis of randomised controlled trials in human adults with overweight or obesity, with and without type 2 diabetes. The authors state that five trials covering 4,746 unique participants were included.
The authors describe the review as PRISMA 2020-compliant and registered in PROSPERO (CRD420261380458), with searches of PubMed, Embase, Cochrane CENTRAL, ScienceDirect, ClinicalTrials.gov and WHO ICTRP to 30 June 2026 for trials comparing CagriSema with semaglutide 2.4 mg or placebo. Results were pooled in two prespecified comparator strata using random-effects models with a Hartung-Knapp-Sidik-Jonkman small-sample adjustment, prediction intervals, leave-one-out and phase-3a-restricted sensitivity analyses, and trial sequential analysis.
What it reported
Against semaglutide 2.4 mg, the pooled estimate for CagriSema was a mean difference of -6.89 percentage points in weight loss (95% CI -8.70 to -5.06; I² = 33%; prediction interval -8.91 to -4.86), with an absolute body-weight reduction of -7.16 kg (95% CI -9.15 to -5.17) and a body-mass index reduction of -2.41 kg/m² (95% CI -2.83 to -1.99). The authors report roughly twice the likelihood of reaching a 20% reduction (RR 2.10, 95% CI 1.78 to 2.47) and a further fall in waist circumference of -4.07 cm (95% CI -5.10 to -3.04).
No incremental glycaemic benefit was detected: the interval for glycated haemoglobin was -0.07 (95% CI -0.14 to 0.01), and fasting plasma glucose intervals lay entirely within prespecified minimal important differences. Injection-site reactions were more frequent (RR 3.14, 95% CI 1.42 to 6.96), while gastrointestinal adverse events were not significantly increased under the primary model (RR 1.09, 95% CI 0.97 to 1.21).
Reported dosing
The only regimen stated in the abstract is the comparator: semaglutide 2.4 mg monotherapy, given to adults with overweight or obesity, with or without type 2 diabetes, in the included randomised trials. The abstract does not report the cagrilintide or CagriSema dose, the dosing frequency, the route of administration, or the treatment duration in the pooled trials.
Limitations
The analysis pools five trials, so the evidence base is small, and the authors state that it is insufficient to determine whether serious adverse events or neoplasms differ between treatments. They also state that long-term durability, cardiovascular outcomes and body composition remain undetermined.
A meta-analysis inherits the design limits of its included trials, and heterogeneity was present (I² = 33%) for the primary weight-loss estimate. The abstract does not report funding sources, author affiliations, participant characteristics beyond overweight or obesity with or without type 2 diabetes, or the individual trial dosing schedules.
Regulatory context
Cagrilintide, an amylin analogue also referred to as AM833 or NNC0174-0833 and coformulated with semaglutide as CagriSema, is not an FDA-approved drug for any use. That status comes from the site's regulatory review rather than from this publication.
Study-reported dosing
| Regimen as reported | Population | Route | Source |
|---|---|---|---|
| semaglutide 2.4 mg monotherapyThe abstract states this comparator dose but does not report the cagrilintide or CagriSema dose, frequency, route, or treatment duration. | adults with overweight or obesity, with or without type 2 diabetes, in the comparator arms of the included randomised controlled trials | Not stated |
Claims and where they come from
Each statement below is followed by the passage of the source record it was checked against.
The review pooled five randomised trials covering 4,746 unique participants.
“Five trials (4,746 unique participants) were included.”
CagriSema was associated with greater absolute weight and body-mass index reductions than semaglutide 2.4 mg.
“a greater absolute reduction in body weight (-7.16 kg, 95% CI -9.15 to -5.17) and in body-mass index (-2.41 kg/m², 95% CI -2.83 to -1.99)”
Participants on CagriSema were about twice as likely to reach a 20% weight reduction.
“roughly twice the likelihood of reaching a 20% reduction (RR 2.10, 95% CI 1.78 to 2.47)”
No incremental glycaemic benefit was detected for the combination.
“No incremental glycaemic benefit was detected, with intervals for glycated haemoglobin (-0.07, 95% CI -0.14 to 0.01)”
Injection-site reactions were more frequent, while gastrointestinal events were not significantly increased in the primary model.
“Injection-site reactions were more frequent (RR 3.14, 95% CI 1.42 to 6.96); gastrointestinal adverse events were not significantly increased under the primary model (RR 1.09, 95% CI 0.97 to 1.21).”
The authors state the evidence cannot resolve serious adverse events, neoplasms, durability, cardiovascular outcomes or body composition.
“The evidence is insufficient to determine whether serious adverse events or neoplasms differ between treatments, and long-term durability, cardiovascular outcomes and body composition remain undetermined.”
Common questions
What comparison did this meta-analysis make?
The authors compared CagriSema, described as a fixed-dose combination of cagrilintide and semaglutide, with semaglutide 2.4 mg monotherapy or placebo, pooling effects within two prespecified comparator strata.
Did the combination improve blood-sugar measures?
No incremental glycaemic benefit was detected. The interval for glycated haemoglobin was -0.07 (95% CI -0.14 to 0.01), and fasting plasma glucose intervals lay entirely within prespecified minimal important differences.
What safety signals were reported?
Injection-site reactions were more frequent (RR 3.14, 95% CI 1.42 to 6.96). Gastrointestinal adverse events were not significantly increased under the primary model (RR 1.09, 95% CI 0.97 to 1.21), and the authors state the evidence is insufficient to compare serious adverse events or neoplasms.
Does the abstract state how CagriSema was dosed?
No. The abstract names the semaglutide 2.4 mg comparator dose but does not report the CagriSema or cagrilintide regimen, frequency, or route used in the included trials.
Source
- 1.CagriSema versus Semaglutide 2.4 mg monotherapy for weight management in adults with overweight or obesity, with or without type 2 diabetes: a systematic review, meta-analysis, and trial sequential analysis — Frontiers in endocrinology (2026)Meta-analysishumann=4746PMID 42890523DOI 10.3389/fendo.2026.1903335