The signal in the records
Adults with type 2 diabetes who began taking levothyroxine, or LT4, had a higher incidence of major adverse cardiovascular events, known as MACE, than matched adults who did not use the drug, according to a retrospective cohort study. The analysis found an association, not proof that levothyroxine caused the events.
MACE comprised three outcomes: a nonfatal heart attack, a nonfatal stroke, or a hospital admission for heart failure. The researchers also reported the stroke and heart failure components separately, and both were more common among LT4 users than matched nonusers.
How the comparison was made
The researchers used the multi-institutional Chang Gung Research Database, drawing on records from 2006 through 2017. They studied new LT4 users and excluded patients with prior LT4 exposure or prior MACE, then matched each user with one nonuser by age, sex and index date.
Follow-up began on the index date and continued until the first cardiovascular event or 31 December 2017. The analysis assessed baseline illnesses, other medicines and laboratory measures, and used Cox models to estimate hazard, meaning the rate at which events occurred over time, in the matched cohort.
The supplied analysis does not report the number of people in either group, the number of events, incidence rates, hazard ratios, confidence intervals or p-values. The direction of the finding is therefore available, but not the size of the difference or how precisely it was estimated.
The pattern across patient groups
Prespecified subgroup analyses examined age, sex, hypertension, diabetic microvascular complications and end-stage renal disease. Within those analyses, LT4 use, older age, male sex, hypertension, diabetic microvascular complications and end-stage renal disease were each associated with increased MACE risk.
The supplied results do not include the figures needed to compare the strength of those associations across the groups. They show which characteristics were linked with higher MACE risk, but not whether any one subgroup had a reliably larger or smaller effect than another.
What the finding can and cannot say
The authors did not interpret the result as evidence that levothyroxine itself was responsible. They said the increased MACE risk appeared to be related to inadequately controlled hypothyroidism rather than LT4 itself. They emphasized achieving and maintaining euthyroidism, or normal thyroid function, through careful LT4 dosing and active thyroid-function monitoring.
That distinction matters because the comparison was not randomized. People taking LT4 may differ from nonusers in ways linked to both thyroid treatment and cardiovascular outcomes, and the supplied material does not give enough detail to show how fully comorbidities, other medicines or laboratory measures were handled. The retrospective design cannot establish that LT4 caused MACE, or that inadequately controlled hypothyroidism caused the association.
The analysis also leaves several questions unanswered. It does not say how inadequate thyroid control was defined or tracked, how LT4 dose or adherence varied, or how often thyroid function was checked. It also does not show whether achieving euthyroidism reduced cardiovascular events, because monitoring and thyroid control were recommendations rather than tested treatments.
A study tied to one database
The study concerns adults with type 2 diabetes represented in the Chang Gung Research Database, so the supplied evidence cannot show how broadly the association applies beyond that population. The datasets are not publicly available because of institutional data-use agreements and patient-privacy restrictions; access is fee-based, limited to a secure on-site environment, and the data cannot be transferred outside the institution.
The article is a peer-reviewed journal paper with publication and version-of-record dates of 21 August 2026. It reports support from Chang Gung Memorial Hospital grants CMRPG3M2141 and CFRPG3L0031, and the authors declared no competing interests. The article also indicates that supplementary material is available, although its contents were not included in the supplied text.
Paper data and sources
Original title: Association of inadequately controlled hypothyroidism with major adverse cardiovascular events in type 2 diabetes patients receiving levothyroxine: a retrospective cohort study.
Authors: Yi-Hsuan Lin, Chih-Wei Hsu, Pi-Hua Liu et al.
Journal/Repository: Endocrine
Status: Peer-reviewed
First online: 2026-08-21
DOI: 10.1007/s12020-026-04651-2
Original paper · Full text