Cardiovascular outcomes and rates of fractures and falls among patients with brand-name versus generic L-thyroxine use

Juan P. Brito, Joseph S. Ross, Yihong Deng, Lindsey Sangaralingham, David J. Graham, Yandong Qiang, Zhong Wang, Xiaoxi Yao, Liang Zhao, Robert C. Smallridge, Victor Bernet, Nilay D. Shah, Kasia J. Lipska

Research output: Contribution to journalArticlepeer-review


Purpose: To compare cardiovascular outcomes and rates of fractures and falls among patients with persistent brand-name versus generic L-thyroxine use. Methods: Retrospective, 1:1 propensity-matched longitudinal study using a national administrative claims database to examine adults (≥18 years) who initiated either brand or generic L-thyroxine between 2008 and 2018, censored at switch or discontinuation of L-thyroxine formulation or disenrollment from the health plan. Main outcome measures included rates of hospitalization for atrial fibrillation, myocardial infarction, congestive heart failure, stroke, spine and hip fractures, and rate of falls in the outpatient or inpatient setting. Hospitalizations for pneumonia were used as a negative control. Results: 195,046 adults initiated treatment with L-thyroxine between 2008 and 2017: 87% generic and 13% brand formulations. They were mostly women (76%), young (94.6% under age 65), white (66%), and 47% had baseline thyroid stimulating hormone levels between 4.5 and 9.9 mIU/L. Among 35,667 propensity-matched patients, there were no significant differences between patients treated with brand versus generic L-thyroxine in atrial fibrillation (HR 0.96, 0.58–1.60), myocardial infarction (HR 0.66, 0.39–1.14), congestive heart failure (HR 1.30, 0.78–2.16), stroke (0.72, 0.49–1.06), spine (HR 0.87, 0.38–1.99) and hip fractures (HR 0.86, 0.26–2.82), or fall outcomes (HR 1.02, 0.14–7.32). Hospitalization rates for pneumonia (used as negative control) did not differ between groups (HR 0.85, 0.61–1.19). There were no interactions between brand versus generic L-thyroxine, these outcomes, and thyroid cancer, age, or L-thyroxine dose subgroups. Conclusions: We found no significant differences in cardiovascular outcomes and rates of falls and fractures for patients who filled brand versus generic L-thyroxine.

Original languageEnglish (US)
Pages (from-to)592-602
Number of pages11
Issue number3
StatePublished - Dec 2021


  • Brand
  • Generic
  • Hypothyroidism
  • Levothyroxine

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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