The effect of different levothyroxine administration regimens on thyroid hormone levels: a systematic review, pairwise, and network meta-analysis

ABSTRACT

Introduction

This systematic review aimed to compare the effect of alternative levothyroxine administration regimens on thyroid hormone levels and patient-reported outcomes (PROs) among adults with hypothyroidism.

Methods

We searched PubMed, Embase, CENTRAL, CINAHL, LILACS, SciELO, Scopus, Web of Science, OpenGrey, ProQuest, ClinicalTrials.gov, and ICTRP from inception to May/2023 for randomized controlled trials (RCTs). We assessed the risk of bias with Cochrane Risk of Bias 2.0 tool. We analyzed TSH levels by pairwise and network meta‐analyses (NMA). The FT4 levels and PROs were qualitatively assessed.

Results

We included 14 RCTs (906 participants) comparing different regimens, as bedtime vs. before breakfast. A total of 12 RCTs were at high risk of bias. Seven RCTs were included in the TSH meta-analysis, where the mean difference (MD) and 95% confidence interval (CI) were as follows: bedtime vs before breakfast (4 RCTs) 0.69 (−1.67–3.04), I² = 92%, very low certainty evidence; weekly dose vs before breakfast (2 RCTs) 1.68 (0.94–2.41), I² = 0%, low certainty evidence; and at breakfast vs before breakfast (1 RCT) 0.65 (−1.11–2.41), very low certainty evidence. The NMA showed no evidence of differences in TSH level with different regimens.

Conclusion

The evidence is insufficient to determine the most effective levothyroxine administration regimen for hypothyroidism.

Systematic review registration

PROSPERO – CRD42021279375

KEYWORDS:

• Administration regimen
• hypothyroidism
• levothyroxine
• meta-analysis
• systematic review
• thyroid hormones

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions statement

BV Bianchini: Conceptualization, Methodology, Formal analysis, Investigation, Writing – Original Draft, Writing – Review & Editing and Project administration; PR de Jesus: Formal analysis and Investigation, Writing – Review & Editing; RGB de Mello: Resources, Writing – Original Draft and Writing – Review & Editing; PK Ziegelmann: Resources, Statistical analysis assistance, Writing – Original Draft and Writing – Review & Editing; KB Filion: Resources, Writing – Original Draft and Writing – Review & Editing; T da Silva Dal Pizzol: Conceptualization, Methodology, Formal analysis, Resources, Writing – Original Draft, Writing – Review & Editing and Supervision.

Acknowledgments

Librarian Viviane Castanho, from Federal University of Rio Grande do Sul, for supervising search strategy process and translating search strings from one database to another. This work was previously presented as an abstract at a conference (International Conference on Pharmacoepidemiology 2023).

Additional information

Funding

This paper was not funded.