CagriSema (Amylin + GLP-1) Achieves 11 kg More Weight Loss Than Semaglutide Alone
CagriSema (cagrilintide/semaglutide) produced 11 kg more absolute weight loss than semaglutide monotherapy in a meta-analysis of 4 RCTs with 4,419 patients, but with more GI side effects.
Quick Facts
What This Study Found
CagriSema vs comparators: additional -11 kg weight, -9.41 cm waist, -7.06 mmHg systolic BP. Cohen's d for weight: -1.38. GI adverse events 32% more frequent (RR 1.32). 4 RCTs, n=4,419.
Key Numbers
How They Did This
Systematic review and meta-analysis of 4 RCTs from MEDLINE, Web of Science, Scopus, and Cochrane Library through July 2025, with GRADE assessment.
Why This Research Matters
If validated long-term, CagriSema could become the most effective obesity drug available, addressing a key unmet need for patients who don't lose enough weight on GLP-1 monotherapy.
The Bigger Picture
The amylin + GLP-1 combination represents the next evolution in peptide-based obesity therapy, combining two satiety peptide pathways for enhanced weight loss.
What This Study Doesn't Tell Us
High heterogeneity (I²=94.8%). Only 4 RCTs available. Long-term outcomes unknown. GI tolerability may limit real-world effectiveness. Cost may restrict access.
Questions This Raises
- ?Will CagriSema's weight loss durability exceed semaglutide's?
- ?Can the GI side effects be managed to maintain adherence?
- ?How does CagriSema compare to tirzepatide for weight loss?
Trust & Context
- Key Stat:
- -11 kg additional loss CagriSema produced 11 kg more weight loss than semaglutide alone across 4 RCTs with over 4,000 patients
- Evidence Grade:
- Systematic review with GRADE assessment of 4 RCTs. Large effect size but high heterogeneity limits certainty.
- Study Age:
- Published in 2025 with studies through July 2025.
- Original Title:
- CagriSema Versus Semaglutide Monotherapy or Placebo for Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with GRADE Assessment.
- Published In:
- The American journal of cardiology (2026)
- Authors:
- Gadelmawla, Ahmed Farid(3), Hammad, Noha(2), Atta, Karim, Diaa, Ahmed, Abouzkaly, Fatma, Soni, Kriti, Kelkar, Raveena, Agrawal, Siddharth P, Ahmed, Raheel, Jain, Hritvik, Passey, Siddhant, Aronow, Wilbert S
- Database ID:
- RPEP-15178
Evidence Hierarchy
Frequently Asked Questions
What is CagriSema?
CagriSema combines two peptide drugs: semaglutide (which targets GLP-1 receptors) and cagrilintide (which targets amylin receptors). Together, they suppress appetite through two different brain pathways, producing more weight loss than either alone.
How much more weight does CagriSema lose vs Ozempic?
In clinical trials, CagriSema produced about 11 kg (24 lbs) more weight loss than semaglutide alone. However, stomach side effects are about 32% more common.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-15178APA
Gadelmawla, Ahmed Farid; Hammad, Noha; Atta, Karim; Diaa, Ahmed; Abouzkaly, Fatma; Soni, Kriti; Kelkar, Raveena; Agrawal, Siddharth P; Ahmed, Raheel; Jain, Hritvik; Passey, Siddhant; Aronow, Wilbert S. (2026). 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 cardiology. https://doi.org/10.1016/j.amjcard.2026.02.030
MLA
Gadelmawla, Ahmed Farid, et al. "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 cardiology, 2026. https://doi.org/10.1016/j.amjcard.2026.02.030
RethinkPeptides
RethinkPeptides Research Database. "CagriSema Versus Semaglutide Monotherapy or Placebo for Obes..." RPEP-15178. Retrieved from https://rethinkpeptides.com/research/gadelmawla-2026-cagrisema-versus-semaglutide-monotherapy
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.