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

Publication Number: 549

Background: Levothyroxine is the standard treatment for hypothyroidism. It has good intestinal absorption and is thus generally recommended to be taken on an empty stomach (i.e., before breakfast (BB)). However, this regimen can compromise treatment adherence, and alternative treatment regimens have been proposed.

Objectives: This systematic review aimed to examine the effect of different levothyroxine administration regimens on thyroid stimulating hormone (TSH) levels among adults with hypothyroidism.

Methods: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, LILACS, SciELO, Scopus, Web of Science, OpenGrey, ProQuest, ClinicalTrials.gov, and International Clinical Trials Registry Platform for randomized controlled trials (RCTs) comparing the effect of different levothyroxine regimens on TSH level. The primary endpoint was TSH level. Two review authors independently selected, extracted data, and assessed the risk of bias (Cochrane Risk of Bias (RoB2) tool), with discrepancies resolved by a third reviewer. Using pairwise and network meta‐analyses (NMA) with random-effects models, we estimated the mean difference (MD) and 95% confidence interval (CI) comparing each treatment regimen.

Results: A total of 14 RCTs (906 participants) compared different administration regimens of levothyroxine: bedtime vs BB (6 RCTs), at breakfast vs BB (4 RCTs), weekly dose vs daily (BB) (3 RCTs), twice-weekly dose vs daily (1 RCT), before dinner vs BB (1 RCT), and an hour before the main meal vs BB (1 RCT). A total of 12 RCTs were at high risk of bias, predominantly because of problems with the randomization process. Seven RCTs were included in the meta-analysis, where the MD (95% CI) between the regimens were: bedtime vs BB (4 RCTs) 0.69 (-1.67; 3.04), I²=92%; weekly dose vs BB (2 RCTs) 1.68 (0.94; 2.41), I²=0%; and at breakfast vs BB (1 RCT) 0.65 (-1.11; 2.41). The NMA showed no evidence of differences in TSH level with any regimen.

Conclusions: This systematic review determined that the available evidence is insufficient to identify the most effective levothyroxine administration regimen for hypothyroidism. The few available studies in this area are at high risk of bias and important heterogeneity is present, including differences in age, treatment times, and outcome measurement.