The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index; 4 of the 7 sources its claims cite were checked for support.
Association of GLP-1 receptor agonist use with cardiovascular outcomes in patients with non-obstructive hypertrophic cardiomyopathy
Open accessOverview
AI snapshot
Written from the paper’s full text.
TL;DR
In a nationwide TriNetX retrospective cohort of 51,528 adults with non-obstructive hypertrophic cardiomyopathy (nHCM), GLP-1 receptor agonist (GLP-1 RA) use for at least six months was associated with lower risk of heart failure exacerbations and sudden cardiac death/ventricular arrhythmias at intermediate and long-term follow-up, and fewer major adverse cardiovascular events by end of follow-up. Safety events were generally modest, with more gastrointestinal adverse events among GLP-1 RA users but low/comparable pancreatitis and less gallbladder disease and acute kidney injury over time.
Key findings
- Among 51,528 included patients, 2,194 were treated with a GLP-1 RA for at least six months; 40.8% of users received more than one agent, with semaglutide most commonly prescribed, followed by tirzepatide, dulaglutide, and liraglutide.
- GLP-1 RA use was associated with a lower cumulative incidence of HF exacerbations and SCD/VA compared with non-use, with event-curve separation becoming more apparent over longer follow-up; GLP-1 RA users also experienced fewer MACE events by the end of follow-up, while early 1-year event rates were comparable between groups.
- Safety outcomes: pancreatitis rates were low and comparable between groups; gastrointestinal adverse events were more frequent among GLP-1 RA users; gallbladder disease and acute kidney injury occurred less frequently among GLP-1 RA users over time.
- At baseline, GLP-1 RA users had higher prevalence of hypertension (71.1% vs 44.5%), diabetes (55.9% vs 10.9%), obesity (58.4% vs 13.6%), and chronic kidney disease (7.4% vs 4.7%), and greater use of beta blockers, diuretics, statins, SGLT-2 inhibitors, and RAAS inhibitors.
Methods
- Retrospective nationwide analysis using the TriNetX Research Network, a global EHR network spanning approximately 30 countries and over 200 healthcare organizations; adults aged ≥18 years with nHCM were included after excluding secondary causes of ventricular hypertrophy, prior study outcomes, missing demographic data, and GLP-1 RA exposure <6 months.
- Exposure was post-diagnosis GLP-1 RA use versus non-use; index date was first recorded GLP-1 RA prescription for users and nHCM diagnosis date for non-users; follow-up ran from index date to most recent recorded healthcare encounter.
- Inverse probability weighting used propensity scores from demographics, comorbidities, and medication use, with stabilized weights trimmed at the 1st and 99th percentiles; relative risks with 95% confidence intervals were reported at 1, 3, and 5 years and over total follow-up, with non-users as reference; safety outcomes were summarized descriptively; analyses used RStudio v5.2.
Limitations
- The paper states that its retrospective observational design introduces possible confounding by indication and residual confounding despite IPW; reliance on EHR-based ICD coding may cause diagnostic and outcome misclassification; medication dose, adherence, and imaging parameters were unavailable; SCD/VA event definitions were not adjudicated; and proportional hazards assumptions were violated, limiting causal inference.
- Evident from the text: safety outcomes were summarized descriptively rather than with comparative adjusted estimates, and the manuscript text does not report numeric relative risks or confidence intervals for the efficacy outcomes, referring instead to Fig. 1.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
4 of 7 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured
- Premisecitation
GLP-1 receptor agonists have shown benefit in heart failure with preserved ejection fraction (HFpEF).
“Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown benefit in HFpEF [4].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [4] Kosiborod, 2023, Semaglutide in patients with heart failure with preserved ejection fraction and obesity, N Engl J Med source
The Conclusions report that semaglutide, a GLP-1 receptor agonist, improved symptoms, physical limitations, and exercise function compared with placebo in patients with HFpEF and obesity. The claim omits the obesity restriction and generalizes from one drug to GLP-1 receptor agonists as a class. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Premisecitation
Clinical variability in HCM can, in part, be explained by the influence of modifiable cardiometabolic risk factors, such as obesity, diabetes, and hypertension.
“This clinical variability can, in part, be explained by the influence of modifiable cardiometabolic risk factors, such as obesity, diabetes, and hypertension [6].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [6] Marian, 2017, Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy, Circ Res source
The Pathogenesis section, under “Determinants of the HCM Phenotypes” (page not provided), says environmental factors contribute to HCM phenotypic variability and that systemic arterial hypertension would be expected to increase hypertrophy severity. It does not identify obesity or diabetes as contributors, so the full list of cardiometabolic risk factors is not supported by our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Premisecitation
Myosin inhibitors failed to improve outcomes in the phase 3 ODYSSEY-HCM trial in patients with non-obstructive hypertrophic cardiomyopathy.
“Despite their success in obstructive HCM, myosin inhibitors failed to improve outcomes in the recent phase 3 ODYSSEY-HCM trial, underscoring the lack of effective therapies for nHCM [2,3].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [2] Desai, 2025, Mavacamten in symptomatic nonobstructive hypertrophic cardiomyopathy, N Engl J Med source
- cites [3] Bilen, 2025
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Findingown data
GLP-1 RA users had greater baseline use of cardiovascular and metabolic therapies, including beta blockers, diuretics, statins, SGLT-2 inhibitors, and RAAS inhibitors, compared with non-users.
“They also demonstrated greater baseline use of cardiovascular and metabolic therapies, including beta blockers, diuretics, statins, sodium-glucose cotransporter-2 inhibitors, and renin-angiotensin-aldosterone system inhibitors (Table 1).”
Quote in the paperNot a substantial claim - Findingown data
Rates of pancreatitis were low and comparable between GLP-1 RA users and non-users throughout follow-up.
“Rates of pancreatitis were low and comparable between groups throughout follow-up.”
Quote in the paperNot a substantial claim- Rests on an assumption: The ICD-based definitions accurately identify nHCM, GLP-1 RA exposure, and study outcomes.
- Rests on an assumption: After IPW, there is no unmeasured confounding between GLP-1 RA users and non-users.
- Findingown data
GLP-1 RA users experienced fewer MACE events by the end of follow-up.
“GLP-1 RA users experienced fewer MACE events by the end of follow-up.”
Quote in the paperSubstantial claim- Rests on an assumption: The ICD-based definitions accurately identify nHCM, GLP-1 RA exposure, and study outcomes.
- Rests on an assumption: After IPW, there is no unmeasured confounding between GLP-1 RA users and non-users.
- Rests on an assumption: The violation of proportional hazards assumptions does not invalidate the reported associations.
- Rests on an assumption: Non-adjudicated event definitions, particularly for SCD/VA, are accurate enough for the reported associations.
- Rests on an assumption: The lack of information on medication dose, adherence, and imaging parameters does not substantially bias the results.
- Findingown data
The analysis identified 124,885 adult U.S. patients with nHCM after excluding those with valvular disease, coarctation of the aorta, and infiltrative cardiomyopathies.
“This retrospective nationwide analysis identified 124,885 adult U.S. patients with nHCM after excluding those with valvular disease, coarctation of the aorta, and infiltrative cardiomyopathies.”
Quote in the paperSubstantial claim - Study design and conductnone given
Proportional hazards assumptions were violated.
“proportional hazards assumptions were violated”
Quote in the paperNot a substantial claim - Study design and conductnone given
Event definitions, particularly for SCD/VA, were not adjudicated.
“Event definitions, particularly for SCD/VA, were not adjudicated”
Quote in the paperSubstantial claim - Study design and conductnone given
Information on medication dose, adherence, and imaging parameters was unavailable.
“information on medication dose, adherence, and imaging parameters was unavailable”
Quote in the paperSubstantial claim - Premisecitation
Non-obstructive HCM shares considerable phenotypic overlap with heart failure with preserved ejection fraction (HFpEF).
“Notably, nHCM shares considerable phenotypic overlap with heart failure with preserved ejection fraction (HFpEF) [1].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Maron, 2022, Diagnosis and evaluation of hypertrophic cardiomyopathy: JACC State-of-the-art Review, J Am Coll Cardiol source
Checked before — its earlier verdict is held back until a new check runs.
- Study design and conductreasoning
The retrospective observational design introduces the possibility of confounding by indication and residual confounding despite IPW.
“Its retrospective observational design introduces the possibility of confounding by indication and residual confounding despite IPW.”
Quote in the paperSubstantial claim
- Probably not a substantial claim. 7
- It may state two separate claims as one. 8
Probably not a substantial claim.
PremisecitationUnfavorable cardiovascular health is associated with substantially higher risks of heart failure and arrhythmias among carriers of pathogenic sarcomeric variants.
“Previous work from the UK Biobank has shown that unfavorable cardiovascular health is associated with substantially higher risks of heart failure and arrhythmias among carriers of pathogenic sarcomeric variants, supporting the concept that cardiometabolic health may modify outcomes in genetically predisposed individuals [7].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [7] Patel, 2025, Cardiovascular health and outcomes in carriers with genetic variants of hypertrophic cardiomyopathy, Mayo Clin Proc source
It may state two separate claims as one.
Findingown dataCompared with non-users, GLP-1 RA users had a higher prevalence of hypertension, diabetes, obesity, and chronic kidney disease.
“Compared with non-users, GLP-1 RA users had a higher prevalence of cardiometabolic comorbidities, including hypertension, diabetes, obesity, and chronic kidney disease.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataGastrointestinal adverse events were more frequently observed among GLP-1 RA users, though absolute event rates remained modest.
“Gastrointestinal adverse events were more frequently observed among GLP-1 RA users, consistent with the known class effect, though absolute event rates remained modest.”
Quote in the paperNot a substantial claim- Rests on an assumption: The ICD-based definitions accurately identify nHCM, GLP-1 RA exposure, and study outcomes.
- Rests on an assumption: After IPW, there is no unmeasured confounding between GLP-1 RA users and non-users.
It may state two separate claims as one.
Findingown dataAfter excluding those with missing demographic data, prior outcomes, or insufficient GLP-1 RA exposure, 51,528 patients were included, of whom 2,194 were treated with GLP-1 RA for at least six months.
“After excluding those with missing demographic data, prior outcomes, or insufficient GLP-1 RA exposure, 51,528 patients were included, of whom 2,194 were treated with GLP-1 RA for at least six months.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataGallbladder disease and acute kidney injury occurred less frequently among GLP-1 RA users compared with non-users over time.
“Gallbladder disease and acute kidney injury occurred less frequently among GLP-1 RA users compared with non-users over time. (Fig. 1 Panel C)”
Quote in the paperNot a substantial claim- Rests on an assumption: The ICD-based definitions accurately identify nHCM, GLP-1 RA exposure, and study outcomes.
- Rests on an assumption: After IPW, there is no unmeasured confounding between GLP-1 RA users and non-users.
It may state two separate claims as one.
Findingown dataSafety analyses using IPW demonstrated low and comparable rates of pancreatitis, gallbladder disease, and acute kidney injury between groups across short-term follow-up intervals.
“Safety analyses using IPW demonstrated low and comparable rates of pancreatitis, gallbladder disease, and acute kidney injury between groups across short-term follow-up intervals.”
Quote in the paperSubstantial claim- Rests on an assumption: The ICD-based definitions accurately identify nHCM, GLP-1 RA exposure, and study outcomes.
- Rests on an assumption: After IPW, there is no unmeasured confounding between GLP-1 RA users and non-users.
It may state two separate claims as one.
Findingown dataEarly event rates at one year were comparable between groups, but longer-term outcomes consistently favored GLP-1 RA users across endpoints.
“Early event rates at one year were comparable between groups; however, longer-term outcomes consistently favored GLP-1 RA users across endpoints. (Fig. 1 Panel B)”
Quote in the paperSubstantial claim- Rests on an assumption: The ICD-based definitions accurately identify nHCM, GLP-1 RA exposure, and study outcomes.
- Rests on an assumption: After IPW, there is no unmeasured confounding between GLP-1 RA users and non-users.
- Rests on an assumption: The violation of proportional hazards assumptions does not invalidate the reported associations.
- Rests on an assumption: Non-adjudicated event definitions, particularly for SCD/VA, are accurate enough for the reported associations.
- Rests on an assumption: The lack of information on medication dose, adherence, and imaging parameters does not substantially bias the results.
It may state two separate claims as one.
Findingown dataGLP-1 RA use was associated with a lower cumulative incidence of HF exacerbations and SCD/VA compared with non-use.
“During follow-up, GLP-1 RA use was associated with a lower cumulative incidence of HF exacerbations and SCD/VA compared with non-use, with separation of event curves becoming more apparent over longer follow-up durations (Fig. 1, Panel B).”
Quote in the paperSubstantial claim- Rests on an assumption: The ICD-based definitions accurately identify nHCM, GLP-1 RA exposure, and study outcomes.
- Rests on an assumption: After IPW, there is no unmeasured confounding between GLP-1 RA users and non-users.
- Rests on an assumption: The violation of proportional hazards assumptions does not invalidate the reported associations.
- Rests on an assumption: Non-adjudicated event definitions, particularly for SCD/VA, are accurate enough for the reported associations.
- Rests on an assumption: The lack of information on medication dose, adherence, and imaging parameters does not substantially bias the results.
Probably not a substantial claim. It may be too vague to check against evidence.
InterpretationcitationThese findings provide a mechanistic framework through which GLP-1 RAs may exert cardioprotective effects in nHCM.
“These findings provide a mechanistic framework through which GLP-1 RAs may exert cardioprotective effects in nHCM.”
Quote in the paperNot a substantial claimProbably not a substantial claim.
Study design and conductreasoningPatients experiencing efficacy outcomes within 6 months of the index date were censored to minimize immortal time bias.
“To minimize immortal time bias, patients experiencing efficacy outcomes within 6 months of the index date were censored.”
Quote in the paperSubstantial claimProbably not a substantial claim.
Study design and conductreasoningInverse probability weighting was applied using propensity scores derived from logistic regression incorporating demographics, comorbidities, and medication use to address baseline differences.
“Given baseline differences between groups, inverse probability weighting (IPW) was applied using propensity scores derived from logistic regression incorporating demographics, comorbidities, and medication use.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductcitationStabilized weights were trimmed at the 1st and 99th percentiles.
“Stabilized weights were trimmed at the 1st and 99th percentiles [5].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [5] Patel, 2025, Clinical outcomes with Mavacamten use in patients with obstructive hypertrophic cardiomyopathy using real-world data, Mayo Clin Proc source
Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
InterpretationreasoningThese factors limit causal inference and warrant cautious interpretation.
“These factors limit causal inference and warrant cautious interpretation.”
Quote in the paperNot a substantial claimProbably not a substantial claim.
Study design and conductnone givenReliance on electronic health record-based ICD coding may result in diagnostic and outcome misclassification.
“Reliance on electronic health record-based ICD coding may result in diagnostic and outcome misclassification”
Quote in the paperSubstantial claim
The paper relies on this without support.
The ICD-based definitions accurately identify nHCM, GLP-1 RA exposure, and study outcomes.
“Clinical conditions and procedures are identified using standardized coding systems, including ICD-10-CM, CPT, and SNOMED.”
The paper relies on this without support.
After IPW, there is no unmeasured confounding between GLP-1 RA users and non-users.
“Given baseline differences between groups, inverse probability weighting (IPW) was applied using propensity scores derived from logistic regression incorporating demographics, comorbidities, and medication use.”
The paper relies on this without support.
The violation of proportional hazards assumptions does not invalidate the reported associations.
“proportional hazards assumptions were violated”
The paper relies on this without support.
Non-adjudicated event definitions, particularly for SCD/VA, are accurate enough for the reported associations.
“Event definitions, particularly for SCD/VA, were not adjudicated”
The paper relies on this without support.
The lack of information on medication dose, adherence, and imaging parameters does not substantially bias the results.
“information on medication dose, adherence, and imaging parameters was unavailable”
Citations
Cites
Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity
Kosiborod, M. N., Abildstrøm, S. Z., Borlaug, B. A., Butler, J., Rasmussen, S., Davies, M., Hovingh, G. K., Kitzman, D. W., Lindegaard, M. L., Møller, D. V., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2306963 · Cited by 1,669 · cited 2×
“Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown benefit in HFpEF [4].”
Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy
Marian, A. J., & Braunwald, E. (2017) · Circulation Research · doi:10.1161/circresaha.117.311059 · Cited by 1,403
Diagnosis and Evaluation of Hypertrophic Cardiomyopathy
Maron, B. J., Desai, M. Y., Nishimura, R. A., Spirito, P., Rakowski, H., Towbin, J. A., Rowin, E. J., Maron, M. S., & Sherrid, M. V. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.12.002 · Cited by 637
Mavacamten in symptomatic nonobstructive hypertrophic cardiomyopathy
Desai, M. Y., Owens, A. T., Abraham, T., Olivotto, I., Garcia-Pavia, P., Lopes, R. D., Elliott, P., Fernandes, F., Verheyen, N., Maier, L., et al. (2025) · New England Journal of Medicine · doi:10.1056/nejmoa2505927 · Cited by 90
Bilen, O., Adler, A., Bastiaenen, R., MacNamara, J. P., Paratz, E. D., Maor, E., Arad, M., Gold, M. E., Patel, N., Pruett, C., et al. (2025) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.125.005502 · Cited by 6
Self-citationPatel, N., Gaonkar, M., Pampana, A., Shetty, N. S., Vekariya, N., Li, P., Arora, G., & Arora, P. (2026) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2025.01.003 · Cited by 2
Self-citationCardiovascular health and outcomes in carriers with genetic variants of hypertrophic cardiomyopathy
Patel, N., Gaonkar, M., Pampana, A., Dhaliwal, J. S., Vekariya, N., Shetty, N. S., Li, P., Kalra, R., Arora, G., & Arora, P. (2026) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2024.12.018 · Cited by 2
Self-citation
Flagged first, then by citations
Cited by
Still being checked.
Metadata
- Authors
- Bal, H. S., Nayak, A., Pampana, A., Malay, S., Upadhyaya, A., Vekariya, N., Arora, G., & Arora, P.
- Affiliations
- University of Alabama at Birmingham (US)
- Venue
- American Journal of Preventive Cardiology
- Publisher
- Elsevier BV
- Published
- 2026-02
- Volume
- 25
- Pages
- 101451
- ISSN
- 2666-6677 (ISSN-L)
- PMC
- PMC12946939
- OpenAlex
- W7126449261
- Semantic Scholar
- 035a6d2bccdde0312873d15e9338c050a29406fb
- Cited by
- 0
- References
- 5
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- American Journal of Preventive Cardiology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Heart, Lung, and Blood Institute
- National Institutes of Health (R01HL160982, K24HL180320, R01HL163081, R01HL163852, R01HL176882)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- GLP-1 receptor agonists, non-obstructive hypertrophic cardiomyopathy, cardiovascular outcomes, drug safety, heart failure
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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A second model labelled each claim on 2026-11-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
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