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doi: 10.1371/journal.pone.0256749 42 LiuC.-Y.YangY.JuW.-N.WangX.ZhangH.-L

Transitioning from weight loss to maintenance Determining goal weight achievement: Lost 10-12% body weight (cagrilintide alone) Lost 15-25% body weight (CagriSema) Weight stable for 4-8 weeks Satisfied with current weight Ready to focus on maintenance Maintenance dose options comparison: Option 1: Continue same dose Keep cagrilintide at 2.4mg weekly Ensures no regain Most conservative approach Highest cost Option 2: Reduce dose slightly Decrease to 1.8-2.0mg weekly Monitor weight for 4 weeks If stable, maintain If gaining, increase back 20-25% cost savings Option 3: Try every 10 days Instead of weekly, inject every 10 days Effectively 30% dose reduction Some maintain weight this way Requires close monitoring Recommendation: Try Option 2 first (reduce to 1.8-2.0mg)

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Analysis of single-cell RNA sequencing Single-cell RNA sequencing (scRNA-seq) data (HRA000425) were downloaded from Genome Sequence Archive (SRA)-Human databases in China National Center for Bioinformation 16 , converted into FASTQ format using fasterq-dump software (sratoolkit 3.0.2, NCBI, NIH, Bethesda, MD, USA), converted into a matrix data file using Cell Ranger software version 3.0.2 (10xGenomics, Pleasanton, CA, USA), converted into Seurat objects using Seurat 5.0.1 software (Satija lab, Lower Manhattan, New York, NY, USA), and plotted for t -distributed stochastic neighbor embedding ( t -SNE) visualization