CagriSema Versus Semaglutide Monotherapy or Placebo for Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with GRADE Assessment. | Pepdox
CagriSema Versus Semaglutide Monotherapy or Placebo for Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with GRADE Assessment.
The American journal of cardiology2026PMID: 41759565
Systematic review and meta-analysis with GRADE quality assessment comparing CagriSema (combined cagrilintide + semaglutide) to semaglutide monotherapy or placebo for obesity across RCTs. Quantifies the incremental weight loss, metabolic improvements, and additional adverse events of adding cagrilintide to semaglutide. Provides GRADE-graded evidence for CagriSema's superiority over semaglutide alone—informing Phase 3 clinical trial prioritization and future regulatory submissions for this next-generation combination obesity therapy.
Abstract
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.