Comparative Study Between the Short-Term Effects of Replacement Therapy with Liquid and Tablet Formulations of...

Background/Objectives: Levothyroxine (L-T4) replacement therapy is essential following total thyroidectomy. While liquid L-T4 formulations exhibit superior pharmacokinetic properties compared to tablets, their specific metabolic impact-particularly on insulin resistance-remains unclear. The aim of this study was to compare the short-term effects of liquid versus tablet L-T4 replacement therapy on insulin resistance indices in recently thyroidectomized women and to identify baseline predictors of metabolic response. Methods: A post hoc analysis included 130 women randomized to receive either liquid or tablet L-T4 after total thyroidectomy. Metabolic parameters-including the homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides-glucose (TyG) index, and triglycerides-to-HDL cholesterol (TG/HDL-C) ratio-were assessed at baseline and after two months. Results: Both L-T4 formulations significantly improved insulin resistance indices over two months. Liquid L-T4 induced a more pronounced reduction in HOMA-IR (treatment effect p = 0.022) and fasting insulin levels (treatment effect p = 0.017) compared to the tablet formulation. No significant between-group differences were observed for TyG index or TG/HDL-C ratio. Changes in insulin resistance markers were independent of body mass index variations and were predicted by baseline metabolic parameters including insulin, glucose, and lipid levels. Conclusions: L-T4 replacement therapy improves insulin resistance markers shortly after thyroidectomy, with the liquid formulation exerting a greater effect on hepatic insulin sensitivity. These findings support the individualized selection of L-T4 formulations to optimize both endocrine and metabolic outcomes post-thyroidectomy.