Glucagon-like peptide-1 receptor agonists and risk for cardiovascular events in older adults treated with levothyroxine: a target trial emulation
Main finding · AF/AflutterResult — go to the resultHazard ratio 1.46 95% CI 1.28–1.67Authors' conclusion
In 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.
Study context
- Population
- Medicare beneficiaries >65 years with T2D on stable-dose levothyroxine ≥6 months before index date, continuous enrollment, without malignant cancer or palliative care in prior year; 15% nationally representative US samplematched cohort
- Participants
- 2,384 vs 2,384
- Exposure
- GLP-1 RA initiation vs SGLT2 inhibitor initiation
- GLP-1RAn = 2,384
- SGLT2n = 2,384reference
- Outcome
- AF/Aflutter
- Follow-up
- Median 1.05 years
Methodological detailsretrospective cohort study, new user, active comparator design, propensity score matching 1:1, per-protocol analysis, inverse-probability-censoring weighted Cox models
- Retrospective cohort study
- New user, active comparator design
- Propensity score matching 1:1
- Per-protocol analysis
- Inverse-probability-censoring weighted Cox models
Main finding
As reported in the abstract
Hazard ratio
1.46
95% CI 1.28–1.67
GLP-1RAvs SGLT2
HR 1.46 (95% CI 1.28–1.67)
Observational data: associations, not effects.
Secondary outcomes
| Outcome | HR (95% CI) | |
|---|---|---|
| Stroke (ischemic stroke or transient ischemic attack) | 1.17 (0.98–1.39) | |
| 0.512Hazard ratio (log scale) |
Sensitivity analyses
- Consistent results restricting outcomes to inpatient visits, with ITT analysis, prevalent new user design, and DPP-4i as active comparator
Original publication
Glucagon-like peptide-1 receptor agonists and risk for cardiovascular events in older adults treated with levothyroxine: a target trial emulation. Cardiovasc Diabetol. Published 24 December 2025. doi:10.
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