Evidence map›Paper›PMID 41444586›Full record

Observational studyCardiovascular diabetology2025

Glucagon-like peptide-1 receptor agonists and risk for cardiovascular events in older adults treated with levothyroxine: a target trial emulation.

Fanxing Du, Naykky M Singh Ospina, Yishan Chen, Juan P Brito, Qing Liu, Stephan Schmidt, Rozalina G McCoy, Brian Cicali, Hui Shao, Tianze Jiao

Abstract readObservational StudyComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Cardiovascular diabetology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Fanxing DuDepartment of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, USA.
Naykky M Singh OspinaDivision of Endocrinology, Department of Medicine, University of Florida, Gainesville, USA.
Yishan ChenDepartment of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, USA.
Juan P BritoDivision of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, USA.
Qing LiuDepartment of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, USA.
Stephan SchmidtDepartment of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, USA.
Rozalina G McCoyDivision of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, USA.
Brian CicaliDepartment of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, USA.
Hui ShaoEmory Global Diabetes Research Center of Woodruff Health Sciences Center, Emory University, Atlanta, USA.
Tianze JiaoDepartment of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, USA. tianzejiao@ufl.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInitiation of Glucagon-Like Peptide-1 receptor agonists (GLP-1RA) in patients with type 2 diabetes (T2D) treated with levothyroxine may decrease the required levothyroxine dose due to weight loss or enhance levothyroxine absorption through delayed gastric emptying. These changes may cause thyroid hormone over-replacement and increased risk of atrial fibrillation/flutter (AF/Aflutter) and stroke. Our study aims to investigate the impact of GLP-1RA initiation on risks of AF/Aflutter and stroke in patients with T2D treated with levothyroxine, compared to sodium-glucose cotransporter 2 (SGLT2) inhibitors.

methodsLeveraging the target trial emulation framework, we conducted a retrospective study using observational data to emulate a new user, active comparator trial examining the effects of initiating GLP-1RA (exposure group) versus SGLT2 inhibitors (control group), with random treatment assignment emulated by propensity score matching with 1:1 ratio. We used a 15% nationally representative sample of U.S. Medicare beneficiaries to identify participants > 65 years, continuously on stable dose of levothyroxine for ≥ 6 months before the index date (i.e., GLP-1RA or SGLT2 inhibitor initiation), with continuous Medicare enrollment, without malignant cancer or palliative care during 1 year before the index date. The primary outcome was AF/Aflutter, and secondary outcome was stroke, including ischemic stroke or transient ischemic attack. We assessed the per-protocol effects of GLP-1RA vs. SGLT2 inhibitors using inverse-probability-censoring weighted Cox proportional hazards models.

resultsAfter matching, the study cohort included 2,384 participants in both GLP-1RA and SGLT2 groups with mean age (SD): 73.3 (5.9) vs. 73.2 (5.8), and 71.5% and 71.8% of female. The median follow-up time was 1.05 years. Compared to SGLT2 inhibitors, initiation of GLP-1RA was associated with higher risk of AF/Aflutter (HR: 1.46; 95% CI: 1.28-1.67), while no statistically significant difference was observed between the two groups for stroke (HR: 1.17; 95% CI: 0.98-1.39). Sensitivity analyses showed consistent results, including restricting outcomes to inpatient visits, conducting an intention-to-treat analysis, applying a prevalent new user design, and substituting SGLT2 inhibitors with dipeptidyl peptidase-4 (DPP4) inhibitors as the active comparator.

conclusionsIn patients with T2D historically treated with stable doses of levothyroxine, GLP-1RA initiation was associated with a higher risk of AF/Aflutter. Further research is warranted to investigate the potential roles of weight loss, TSH fluctuations, and levothyroxine dose adjustment after GLP-1RA in mediating the cardiovascular risk.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsIncretinsSodium-Glucose Transporter 2 InhibitorsStrokeThyroxineAgedAged, 80 and overAge FactorsAtrial FibrillationDatabases, FactualFemaleGlucagon-Like Peptide-1 ReceptorHeart Disease Risk FactorsHumansMaleGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsIncretinsSodium-Glucose Transporter 2 InhibitorsThyroxineatrial fibrillation or flutterGLP-1RAlevothyroxineSGLT2 inhibitorsstroketarget trial emulation

Identifiers

PMID41444586
PMCPMC12729143

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.