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CagriSema (Amylin + GLP-1) Achieves 11 kg More Weight Loss Than Semaglutide Alone

RPEP-151782026Gadelmawla, 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
evidence
The takeaway

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.

-11 kg additional loss

CagriSema produced 11 kg more weight loss than semaglutide alone across 4 RCTs with over 4,000 patients

What the researchers 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.

Why it 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.

How the study worked

Systematic review and meta-analysis of 4 RCTs from MEDLINE, Web of Science, Scopus, and Cochrane Library through July 2025, with GRADE assessment.

What this study cannot 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.

How to read the evidence

Systematic review with GRADE assessment of 4 RCTs. Large effect size but high heterogeneity limits certainty.

When this study was published

Published in 2025 with studies through July 2025.

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.

Questions still open

  • 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?

Common 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.

Read the original research

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

View on PubMed ↗Publisher’s paper ↗

Citation

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