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.

Gadelmawla, Ahmed Farid et al.·The American journal of cardiology·2026·
RPEP-151782026RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Not classified
Evidence
Not graded
Sample
Not reported

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)
Database ID:
RPEP-15178

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

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

RPEP-15178·https://rethinkpeptides.com/research/RPEP-15178

APA

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.