---
title: "Factors Driving Weight Loss Variability with GLP-1 Receptor Agonists and Dual Agonists in Obesity:"
id: "pubmed-42733128"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42733128"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42733128/"
doi: "10.1111/cob.70112"
published_at: "2026-10-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Factors Driving Weight Loss Variability with GLP-1 Receptor Agonists and Dual Agonists in Obesity:
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42733128
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42733128/)
- **DOI:** [10.1111/cob.70112](https://doi.org/10.1111%2Fcob.70112)
- **Published At:** 2026-10-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This meta-regression examined interindividual heterogeneity in weight loss achieved with **GLP-1RAs** and dual agonists in adults with overweight or obesity, using randomized trials identified through systematic searches up to February 1, 2026 and following PRISMA guidance. - The analysis included 32 eligible trials with 40,408 participants. Analyses were performed using R software. - Pooled weighted mean percentage weight reduction across trials was 9.36% (95% CI 7.92%–10.80%), but interstudy heterogeneity was very high (I2 = 99.6%, p < 0.001). - Subgroup analyses indicated greater weight loss with **GLP-1/GIP dual agonists (tirzepatide)** compared with other agonist classes, and with longer treatment duration (≥ 72 weeks). - Meta-regression identified baseline **anxiety/depression** as positively associated with weight-loss efficacy (β = 2.44, p < 0.001), with this model explaining much of between-study variance (R2 = 81.34%). - Presence of metabolic comorbidities — **type 2 diabetes mellitus (T2DM)**, **obstructive sleep apnea (OSA)**, and **MAFLD** (metabolic dysfunction–associated fatty liver disease) — were negatively correlated with treatment response (all p < 0.05). - Risk of bias across included trials was assessed with RoB-2; figures and sensitivity analyses (including SD imputation approaches) were reported. - The authors conclude that emotional state and specific metabolic comorbidities are important mediators of interindividual differences in weight-loss response to GLP-1RAs and dual agonists, supporting more personalized obesity management. - The publication is a 2026 review in Clinical Obesity (PMID 42733128, PMCID PMC13572569, DOI 10.1111/cob.70112).
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliation * 1 Department of Endocrinology, Peking University First Hospital, Beijing, China. * PMID: **42733128** * PMCID: [ PMC13572569 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13572569/) * DOI: [ 10.1111/cob.70112 ](https://doi.org/10.1111/cob.70112) Item in Clipboard Review # Weight Reduction Heterogenicity and Mediators of GLP-1RAs and Dual Agonists for Individuals With Obesity: A Meta-Analysis Difei Lu et al. Clin Obes. 2026 Oct. Show details Display options Display options Format Abstract PubMed PMID Clin Obes Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Clin+Obes%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Clin+Obes%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42733128/) . 2026 Oct;16(5):e70112. doi: 10.1111/cob.70112. ### Authors [Difei Lu](https://pubmed.ncbi.nlm.nih.gov/?term=Lu+D&cauthor_id=42733128)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42733128/#short-view-affiliation-1 "Department of Endocrinology, Peking University First Hospital, Beijing, China."), [Na Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+N&cauthor_id=42733128)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42733128/#short-view-affiliation-1 "Department of Endocrinology, Peking University First Hospital, Beijing, China."), [Zhenfang Yuan](https://pubmed.ncbi.nlm.nih.gov/?term=Yuan+Z&cauthor_id=42733128)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42733128/#short-view-affiliation-1 "Department of Endocrinology, Peking University First Hospital, Beijing, China."), [Ying Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+Y&cauthor_id=42733128)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42733128/#short-view-affiliation-1 "Department of Endocrinology, Peking University First Hospital, Beijing, China.") ### Affiliation * 1 Department of Endocrinology, Peking University First Hospital, Beijing, China. * PMID: **42733128** * PMCID: [ PMC13572569 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13572569/) * DOI: [ 10.1111/cob.70112 ](https://doi.org/10.1111/cob.70112) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual agonists have become pivotal options for obesity, but marked weight loss heterogeneity remains poorly understood. This meta-regression analysis aimed to identify factors influencing this heterogeneity. We searched Medline, Embase, The Cochrane Library, and Web of Science up to February 1, 2026, enrolling 32 eligible trials (40 408 participants) following PRISMA guidelines. Meta-regression and subgroup analyses were performed using R software. Pooled analysis showed that GLP-1RAs and dual agonists achieved a weighted mean weight reduction of 9.36% (95% CI 7.92%-10.80%), with high interstudy heterogeneity (I2 = 99.6%, p < 0.001). Subgroup analyses revealed that GLP-1/GIP dual agonists (tirzepatide) and longer treatment duration (≥ 72 weeks) yielded superior weight-lowering effects. Meta-regression demonstrated that baseline anxiety/depression was positively associated with weight loss efficacy (β = 2.44, p < 0.001, R2 = 81.34%). Comorbid Type 2 diabetes mellitus (T2DM), obstructive sleep apnea (OSA) and metabolic dysfunction-associated fatty liver disease (MAFLD) were negatively correlated with treatment response (all p < 0.05). Emotional state and metabolic comorbidities including T2DM, OSA and MAFLD are important influencing factors of the interindividual differences of weight loss efficacy of GLP-1RAs and dual agonists, providing evidence for personalized obesity management. **Keywords:** glucagon‐like peptide‐1 receptor agonists; meta‐regression; tirzepatide; weight reduction. © 2026 World Obesity Federation. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement The authors declare no conflicts of interest. ## Figures [ ![FIGURE 1](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/fa6ddc0205f3/COB-16-e70112-g006.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/f9d846d0ba2e/COB-16-e70112-g006.webp) ** FIGURE 1 ** Flow chart of trial selection. ** FIGURE 1 ** Flow chart of trial selection. **FIGURE 1** Flow chart of trial selection. [ ![FIGURE 2](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/31eb66f4d39b/COB-16-e70112-g008.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/e72584c36cd4/COB-16-e70112-g008.webp) ** FIGURE 2 ** Risk of bias analysis using… ** FIGURE 2 ** Risk of bias analysis using RoB‐2 ( _n_ = 32). **FIGURE 2** Risk of bias analysis using RoB‐2 (_n_ = 32). [ ![FIGURE 3](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/687561fc9a33/COB-16-e70112-g005.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/ea95eecd2f3f/COB-16-e70112-g005.webp) ** FIGURE 3 ** Forest plot of the weight… ** FIGURE 3 ** Forest plot of the weight loss effect in individuals with overweight/obesity. **FIGURE 3** Forest plot of the weight loss effect in individuals with overweight/obesity. [ ![FIGURE 4](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/c8588ebdca06/COB-16-e70112-g002.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/9dcd1139edbe/COB-16-e70112-g002.webp) ** FIGURE 4 ** Subgroup analysis of the weight… ** FIGURE 4 ** Subgroup analysis of the weight loss effect in individuals with overweight/obesity using GLP‐1RA,… **FIGURE 4** Subgroup analysis of the weight loss effect in individuals with overweight/obesity using GLP‐1RA, GLP‐1/GCGR dual agonists and GLP‐1/GIP dual agonists. [ ![FIGURE 5](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/75b311f24abb/COB-16-e70112-g001.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/30896c947741/COB-16-e70112-g001.webp) ** FIGURE 5 ** Subgroup analysis of the weight… ** FIGURE 5 ** Subgroup analysis of the weight loss effect in individuals with overweight/obesity using semaglutide… **FIGURE 5** Subgroup analysis of the weight loss effect in individuals with overweight/obesity using semaglutide and liraglutide. [ ![FIGURE 6](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/0f19128e7184/COB-16-e70112-g003.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/8325b78fff41/COB-16-e70112-g003.webp) ** FIGURE 6 ** Subgroup analysis of the weight… ** FIGURE 6 ** Subgroup analysis of the weight loss effect in individuals with overweight/obesity according to… **FIGURE 6** Subgroup analysis of the weight loss effect in individuals with overweight/obesity according to different treatment durations. [ ![FIGURE 7](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/40914a12cfce/COB-16-e70112-g004.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/87f0faae553b/COB-16-e70112-g004.webp) ** FIGURE 7 ** Subgroup sensitivity analysis based on… ** FIGURE 7 ** Subgroup sensitivity analysis based on the standard deviation (SD) data source, comparing studies… **FIGURE 7** Subgroup sensitivity analysis based on the standard deviation (SD) data source, comparing studies using coefficient of variation (CV) = 0.5 for imputation of the standard deviation (SD) of unreported weight loss and studies using reported SD. [ ![FIGURE 8](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/4a9e2f3f08eb/COB-16-e70112-g007.gif) ](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4a2/13572569/018511b78760/COB-16-e70112-g007.webp) ** FIGURE 8 ** Treatment effects for weight reduction… ** FIGURE 8 ** Treatment effects for weight reduction by mean difference in potential mediators. The size… **FIGURE 8** Treatment effects for weight reduction by mean difference in potential mediators. The size of each trial's circle is proportional to the inverse of the variance of its log hazard ratio. The solid line refers to meta‐regression slope, and shaded area refers to point estimates and 95% confidence bands from the meta‐regression analyses. A red line refers to statistical significance. BMI, body mass index; DM, diabetes mellitus; HT, hypertension; OSA, obstructive sleep apnea; MAFLD, metabolic‐dysfunction associated fatty liver disease; OA, osteoarthritis. All figures (8) [See this image and copyright information in PMC](https://pubmed.ncbi.nlm.nih.gov/42733128/) ## Similar articles * [ Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA. ](https://pubmed.ncbi.nlm.nih.gov/40685589/) Sinha B, Ghosal S.Sinha B, et al.Obesity (Silver Spring). 2025 Nov;33(11):2046-2054. doi: 10.1002/oby.24360. Epub 2025 Jul 20.Obesity (Silver Spring). 2025.PMID: 40685589 * [ The quantity, quality and findings of network meta-analyses evaluating the effectiveness of GLP-1 RAs for weight loss: a scoping review. ](https://pubmed.ncbi.nlm.nih.gov/40580049/) Nunns M, Febrey S, Buckland J, Abbott R, Whear R, Bethel A, Boddy K, Shaw L, Coon JT, Melendez-Torres GJ.Nunns M, et al.Health Technol Assess. 2025 Jun;30(63):1-73. doi: 10.3310/SKHT8119.Health Technol Assess. 2025.PMID: 40580049Free PMC article. * [ GLP-1 Receptor/Dual Agonists for Weight Loss: A Systematic Review and Network Meta-Analysis of RCTs. ](https://pubmed.ncbi.nlm.nih.gov/41872986/) Vienghirun J, Sawangjit R, Suttiruksa S, Chaiyakunapruk N, Jinathongthai P, Khunti K, Lee SWH.Vienghirun J, et al.Diabetes Obes Metab. 2026 Jun;28(6):5043-5057. doi: 10.1111/dom.70698. Epub 2026 Mar 23.Diabetes Obes Metab. 2026.PMID: 41872986 * [ Tirzepatide for adults living with obesity. ](https://pubmed.ncbi.nlm.nih.gov/41161687/) Franco JV, Guo Y, Varela LB, Aqra Z, Alhalahla M, Medina Rodriguez M, Salvador Oscco EL, Patiño Araujo B, Banda S, Escobar Liquitay CM, Bracchiglione J, Meza N, Madrid E.Franco JV, et al.Cochrane Database Syst Rev. 2025 Oct 30;10(10):CD016018. doi: 10.1002/14651858.CD016018.Cochrane Database Syst Rev. 2025.PMID: 41161687 * [ Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies. ](https://pubmed.ncbi.nlm.nih.gov/40196933/) Thomsen RW, Mailhac A, Løhde JB, Pottegård A.Thomsen RW, et al.Diabetes Obes Metab. 2025 Apr;27 Suppl 2(Suppl 2):66-88. doi: 10.1111/dom.16364. Epub 2025 Apr 8.Diabetes Obes Metab. 2025.PMID: 40196933Free PMC article.Review. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42733128) ## References 1. 1. Pedersen S. D., Manjoo P., Dash S., Jain A., Pearce N., and Poddar M., “Pharmacotherapy for Obesity Management in Adults: 2025 Clinical Practice Guideline Update,” CMAJ 197, no. 27 (2025): E797–E809. - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC12350384/) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/40789597/) 2. 1. Grill H. J., “A Role for GLP‐1 in Treating Hyperphagia and Obesity,” Endocrinology 161, no. 8 (2020): bqaa093. - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7899438/) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/32516384/) 3. 1. Wilding J. P. H., Batterham R. L., Calanna S., et al., “STEP 1 Study Group. Once‐Weekly Semaglutide in Adults With Overweight or Obesity,” New England Journal of Medicine 384, no. 11 (2021): 989–1002. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/33567185/) 4. 1. Jastreboff A. M., Aronne L. J., Ahmad N. N., et al., “SURMOUNT‐1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity,” New England Journal of Medicine 387, no. 3 (2022): 205–216. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/35658024/) 5. 1. Ji L., Jiang H., Bi Y., et al., “GLORY‐1 Investigators. Once‐Weekly Mazdutide in Chinese Adults With Obesity or Overweight,” New England Journal of Medicine 392, no. 22 (2025): 2215–2225. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/40421736/) Show all 50 references ## Publication types * Meta-Analysis Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?ter
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