CagriSema Versus Semaglutide Monotherapy or Placebo for Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with GRADE Assessment

Feb 27, 2026The American journal of cardiology

Comparing CagriSema, Semaglutide, and Placebo for Treating Obesity: A Review and Analysis of Clinical Trials

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Abstract

CagriSema therapy resulted in a 11 kg greater absolute weight loss compared to semaglutide or placebo.

CagriSema significantly reduced percent weight loss with a Cohen's d of -1.38.
Patients on CagriSema experienced a greater reduction in waist circumference, averaging -9.41 cm.
Systolic blood pressure decreased by an average of -7.06 mmHg in those receiving CagriSema.
Gastrointestinal adverse events were more frequent with CagriSema, indicated by a relative risk of 1.32.
CagriSema may achieve superior weight reduction compared to semaglutide monotherapy or placebo.

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The obesity epidemic is a major health burden that enhances susceptibility to a broad spectrum of metabolic-associated comorbidities, ranging from fatty liver disease and endocrine dysfunction to traditional risks like type 2 diabetes mellitus and cardiovascular disease. Glucagon-like peptide-1 receptor agonists, including semaglutide, facilitate weight loss alongside glucose metabolism. The dual therapy CagriSema, which combines semaglutide with cagrilintide was developed. We systematically searched MEDLINE (via PubMed), Web of Science, Scopus, and Cochrane Library, from inception to July 2025, for randomized controlled trials (RCTs) comparing CagriSema with semaglutide monotherapy or placebo in patients with obesity. Four RCTs (n=4,419) were included (CagriSema: 3,055; control: 1,364). Pooled analysis showed that CagriSema significantly reduced percent weight loss (Cohen's d: -1.38; 95% CI: -1.84 to -0.91; I² = 94.8%). CagriSema also resulted in greater absolute weight loss (MD: -11 kg), waist circumference (MD: -9.41 cm), and systolic blood pressure (MD: -7.06 mmHg). Gastrointestinal adverse events were more frequent (RR: 1.32). CagriSema therapy was associated with superior weight reduction compared with semaglutide or placebo. In conclusion, CagriSema achieves greater weight loss than semaglutide or placebo but increases gastrointestinal adverse events, warranting careful tolerability monitoring and longer-term data.