Benefits and Harms of Levothyroxine/liothyronine vs. Levothyroxine Monotherapy for Adult Patients with Hypothyroidism: Systematic Review and Meta-analysis.

Combined therapy with levothyroxine/liothyronine (L-T4/L-T3) has garnered attention among clinicians and patients as a potential treatment alternative to levothyroxine (L-T4) monotherapy. The objective of this study was to compare the benefits and harms of L-T4/L-T3 combined therapy and L-T4 monotherapy for patients with hypothyroidism.
A systematic search in MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials was performed by a librarian from inception date until September 2020. Randomized clinical trials and quasi-experimental studies comparing combined therapy (L-T4/L-T3) versus monotherapy (L-T4) for adult patients with hypothyroidism were considered for inclusion. Independent data extraction was performed by paired reviewers. A meta-analysis comparing standardized mean differences of the effect of each therapy was performed on clinical outcomes and patient preferences. Proportions of adverse events and reactions were assessed narratively.
A total of 1398 references were retrieved from which 18 fulfilled inclusion criteria. Results supported by evidence at low-to-moderate certainty evidence did not display a difference in treatment effect between therapies on clinical status, quality of life, psychological distress, depressive symptoms, and fatigue; all measured with standardized questionnaires. Furthermore, meta-analysis of patient preferences revealed higher proportions of choice for combined therapy (43%) when compared to monotherapy (23%) or having no preference (30%). When evaluating treatment adverse events or adverse reactions, similar proportions were observed between treatment groups; meta-analysis was not possible.
The available evidence at low-to-moderate certainty demonstrates that there is no difference in clinical outcomes between L-T4/L-T3 combined therapy and L-T4 monotherapy for treating hypothyroidism in adults, except for a higher proportion of patient preferring combined therapy. Adverse events and reactions appear to be similar across both groups, however this observation is only narrative. These results could inform shared decision-making conversations between patients with hypothyroidism and their clinicians. PROSPERO Registration ID: CRD42020202658.