---
title: "Semaglutide and Primary Prevention of MACCE in Obese Adults with T2DM and Rheumatoid Arthritis"
id: "pubmed-42334436"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42334436"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42334436/"
doi: "10.1093/ehjcvp/pvag044"
published_at: "2026-08-17T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Semaglutide and Primary Prevention of MACCE in Obese Adults with T2DM and Rheumatoid Arthritis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42334436
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42334436/)
- **DOI:** [10.1093/ehjcvp/pvag044](https://doi.org/10.1093%2Fehjcvp%2Fpvag044)
- **Published At:** 2026-08-17T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This target-trial emulation evaluated whether initiating **semaglutide** reduces incident **major adverse cardiovascular and cerebrovascular events (MACCE)** in obese adults with **type 2 diabetes mellitus (T2DM)** and comorbid **rheumatoid arthritis (RA)** without prior cardiovascular events. - Data came from the TriNetX US database with a new-user design comparing semaglutide initiators to initiators of non-GLP-1 receptor agonist (non-GLP-1RA) second-line glucose-lowering therapies. - Eligible patients were adults (≥18 years) with BMI ≥30 kg/m2, T2DM and RA, and no prior stroke, heart failure (HF), acute coronary syndrome, or coronary revascularization; those with contraindications to GLP-1RAs were excluded. - Propensity-score matching (1:1) produced two balanced cohorts of 1,017 patients each; mean age ~59 years, ~81% women, mean BMI ~38 kg/m2, HbA1c around 6.8%–7.0%. - Primary outcome was incident **MACCE**, a composite of all-cause mortality, myocardial infarction (MI), HF, or stroke, assessed over up to 2 years with Cox models producing hazard ratios (HRs) and 95% CIs. - Semaglutide initiation was associated with lower risk of incident **MACCE** (12.7% vs. 16.5%; HR 0.75, 95% CI 0.60–0.94; P = 0.01). - The reduction in composite events was driven mainly by fewer incident **heart failure** events (8.9% vs. 12.5%; HR 0.69, 95% CI 0.53–0.91; P = 0.007). - Semaglutide users had lower rates of **DMARD escalation** (16.6% vs. 21.6%; HR 0.75, 95% CI 0.60–0.90; P = 0.003), suggesting potential effects on RA management intensity. - No significant differences were reported for all-cause mortality, MI, or stroke between groups. - Authors conclude that among obese adults with T2DM and RA in a primary-prevention setting, semaglutide initiation was associated with reduced incident MACCE largely due to fewer HF events; they recommend prospective studies to confirm causality.
## Clinical Analysis & Structured Key Points
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more resources ](https://pubmed.ncbi.nlm.nih.gov/42334436/#linkout) Title & authors Abstract Conflict of interest statement Similar articles MeSH terms Substances Related information LinkOut - more resources Eur Heart J Cardiovasc Pharmacother Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Eur+Heart+J+Cardiovasc+Pharmacother%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Eur+Heart+J+Cardiovasc+Pharmacother%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42334436/) . 2026 Aug 17;12(5):368-378. doi: 10.1093/ehjcvp/pvag044. # Semaglutide for primary prevention of major adverse cardiac and cerebrovascular events in patients with type 2 diabetes and comorbid rheumatoid arthritis: a target-trial emulation [Farheen Malik](https://pubmed.ncbi.nlm.nih.gov/?term=Malik+F&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Mandar Shah](https://pubmed.ncbi.nlm.nih.gov/?term=Shah+M&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Yu Chang](https://pubmed.ncbi.nlm.nih.gov/?term=Chang+Y&cauthor_id=42334436)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-2 "Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, Tainan 704302, Taiwan."), [Ishmum Chowdhury](https://pubmed.ncbi.nlm.nih.gov/?term=Chowdhury+I&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Sridhar Mangalesh](https://pubmed.ncbi.nlm.nih.gov/?term=Mangalesh+S&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Ahmed Ashraf Morgan](https://pubmed.ncbi.nlm.nih.gov/?term=Morgan+AA&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Ezerioha Pascal](https://pubmed.ncbi.nlm.nih.gov/?term=Pascal+E&cauthor_id=42334436)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-3 "Department of Internal Medicine, Jacobi Medical Center/North Central Bronx, Albert Einstein College of Medicine, Bronx, NY 10467, USA."), [Vishakha Modak](https://pubmed.ncbi.nlm.nih.gov/?term=Modak+V&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Nachum Lebovics](https://pubmed.ncbi.nlm.nih.gov/?term=Lebovics+N&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Suraj Adhikari](https://pubmed.ncbi.nlm.nih.gov/?term=Adhikari+S&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Pei-Lun Lee](https://pubmed.ncbi.nlm.nih.gov/?term=Lee+PL&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Wei-Cheng Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+WC&cauthor_id=42334436)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-4 "Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan."), [Kuan-Yu Chi](https://pubmed.ncbi.nlm.nih.gov/?term=Chi+KY&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#full-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA.") Affiliations Expand ### Affiliations * 1 Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. * 2 Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, Tainan 704302, Taiwan. * 3 Department of Internal Medicine, Jacobi Medical Center/North Central Bronx, Albert Einstein College of Medicine, Bronx, NY 10467, USA. * 4 Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan. * PMID: **42334436** * DOI: [ 10.1093/ehjcvp/pvag044 ](https://doi.org/10.1093/ehjcvp/pvag044) Free article Item in Clipboard # Semaglutide for primary prevention of major adverse cardiac and cerebrovascular events in patients with type 2 diabetes and comorbid rheumatoid arthritis: a target-trial emulation Farheen Malik et al. Eur Heart J Cardiovasc Pharmacother. 2026. Free article Show details Display options Display options Format Abstract PubMed PMID Eur Heart J Cardiovasc Pharmacother Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Eur+Heart+J+Cardiovasc+Pharmacother%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Eur+Heart+J+Cardiovasc+Pharmacother%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42334436/) . 2026 Aug 17;12(5):368-378. doi: 10.1093/ehjcvp/pvag044. ### Authors [Farheen Malik](https://pubmed.ncbi.nlm.nih.gov/?term=Malik+F&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Mandar Shah](https://pubmed.ncbi.nlm.nih.gov/?term=Shah+M&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Yu Chang](https://pubmed.ncbi.nlm.nih.gov/?term=Chang+Y&cauthor_id=42334436)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-2 "Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, Tainan 704302, Taiwan."), [Ishmum Chowdhury](https://pubmed.ncbi.nlm.nih.gov/?term=Chowdhury+I&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Sridhar Mangalesh](https://pubmed.ncbi.nlm.nih.gov/?term=Mangalesh+S&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Ahmed Ashraf Morgan](https://pubmed.ncbi.nlm.nih.gov/?term=Morgan+AA&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Ezerioha Pascal](https://pubmed.ncbi.nlm.nih.gov/?term=Pascal+E&cauthor_id=42334436)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-3 "Department of Internal Medicine, Jacobi Medical Center/North Central Bronx, Albert Einstein College of Medicine, Bronx, NY 10467, USA."), [Vishakha Modak](https://pubmed.ncbi.nlm.nih.gov/?term=Modak+V&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Nachum Lebovics](https://pubmed.ncbi.nlm.nih.gov/?term=Lebovics+N&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Suraj Adhikari](https://pubmed.ncbi.nlm.nih.gov/?term=Adhikari+S&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Pei-Lun Lee](https://pubmed.ncbi.nlm.nih.gov/?term=Lee+PL&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA."), [Wei-Cheng Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+WC&cauthor_id=42334436)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-4 "Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan."), [Kuan-Yu Chi](https://pubmed.ncbi.nlm.nih.gov/?term=Chi+KY&cauthor_id=42334436)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42334436/#short-view-affiliation-1 "Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA.") ### Affiliations * 1 Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. * 2 Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, Tainan 704302, Taiwan. * 3 Department of Internal Medicine, Jacobi Medical Center/North Central Bronx, Albert Einstein College of Medicine, Bronx, NY 10467, USA. * 4 Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan. * PMID: **42334436** * DOI: [ 10.1093/ehjcvp/pvag044 ](https://doi.org/10.1093/ehjcvp/pvag044) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Aims:** Rheumatoid arthritis (RA)-related physical limitations often hinder sustained physical activity and weight management, thereby amplifying cardiovascular risk through adverse metabolic profiles and chronic inflammation. We aimed to assess the effectiveness of semaglutide on the risk of incident major adverse cardiovascular and cerebrovascular events (MACCE) in obese adults with type 2 diabetes mellitus (T2DM) and RA in a primary-prevention setting. **Methods and results:** We emulated a target trial using data from the TriNetX US database, including obese adults [aged ≥18 years; body mass index (BMI) ≥30 kg/m2] with T2DM and comorbid RA and no prior history of stroke, heart failure (HF), acute coronary syndrome, or coronary revascularization. Using a new-user design, we compared patients initiating semaglutide with those initiating non-GLP-1 receptor agonist (GLP-1RA) second-line glucose-lowering therapies. Patients with contraindications to GLP-1RAs were excluded. Propensity-score matching (PS) (1:1) was used to balance baseline covariates. The primary outcome was incident MACCE, defined as a composite of all-cause mortality, myocardial infarction (MI), HF, or stroke. Secondary outcomes included individual MACCE components, HF hospitalization, and disease-modifying anti-rheumatic drug (DMARD) escalation, with Bonferroni correction applied for multiple comparisons. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models over a follow-up of up to 2 years. Between 1 January 2014 and 1 January 2025, we identified 1200 and 2972 patients who initiated semaglutide and non-GLP-1RA therapies, respectively, within 3 months of meeting eligibility. After PS matching, 1017 semaglutide users were compared with 1017 non-GLP-1RA users (mean age 59.5 vs. 59.3 years; women 81.3% vs. 81.0%; mean BMI 38.2 vs. 38.0 kg/m2; HbA1c, 6.8% vs. 7.0%). Semaglutide initiation was associated with a significantly lower risk of incident MACCE compared with non-GLP-1RA therapies (12.7% vs. 16.5%; HR, 0.75; 95% CI, 0.60-0.94; P = 0.01). This benefit was driven primarily by a lower risk of incident HF (8.9% vs. 12.5%; HR, 0.69, 95% CI, 0.53-0.91; P = 0·007). Semaglutide use was also associated with significantly lower DMARD escalation (16.6% vs. 21.6%; HR, 0.75; 95% CI, 0.60-0.90; P = 0.003). No significant differences were observed in all-cause mortality, MI, or stroke. **Conclusion:** Among obese adults with T2DM and comorbid RA, initiation of semaglutide was associated with a reduced risk of incident MACCE, driven predominantly by a reduction in incident HF, in a primary-prevention setting. Prospective studies are needed to confirm these observations and establish causality. **Keywords:** Diabetes; Primary prevention; Rheumatoid arthritis; Semaglutide. © The Author(s) 2026. Published by Oxford University Press on behalf of European Society of Cardiology. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Conflict of interest: None declared. ## Similar articles * [ Superior Cerebrovascular Outcomes with Tirzepatide versus Semaglutide in Diabetic CABG Patients: A Global Network Study of Propensity-Matched Patients. ](https://pubmed.ncbi.nlm.nih.gov/40938549/) Chunduri S, Bidaoui G, Hussein MH, Patel M, Abdelmaksoud A, Mohamed M, Attia A, Tatum D, Borgi J, Toraih EA.Chunduri S, et al.Cardiovasc Drugs Ther. 2026 Jun;40(3):1001-1011. doi: 10.1007/s10557-025-07757-3. Epub 2025 Sep 12.Cardiovasc Drugs Ther. 2026.PMID: 40938549 * [ Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity. ](https://pubmed.ncbi.nlm.nih.gov/40663350/) Lin HT, Tsai YF, Liao PL, Wei JC.Lin HT, et al.JAMA Netw Open. 2025 Jul 1;8(7):e2521016. doi: 10.1001/jamanetworkopen.2025.21016.JAMA Netw Open. 2025.PMID: 40663350 * [ Comparative real-world outcomes of tirzepatide vs semag
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