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Benefits and Harms of Levothyroxine/L-Triiodothyronine Versus Levothyroxine Monotherapy for Adult Patients with Hypothyroidism: Systematic Review and Meta-Analysis.

Millan-Alanis JM, González-González JG, Flores-Rodríguez A, Singh Ospina N, Maraka S, Moreno-Peña PJ, Brito JP, González-Velázquez C, Rodríguez-Gutiérrez R. Benefits and Harms of Levothyroxine/L-Triiodothyronine Versus Levothyroxine Monotherapy for Adult Patients with Hypothyroidism: Systematic Review and Meta-Analysis. Thyroid : official journal of the American Thyroid Association. 2021 Nov 1; 31(11):1613-1625.

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Combined therapy with levothyroxine (LT4)/L-triiodothyronine (LT3) has garnered attention among clinicians and patients as a potential treatment alternative to LT4 monotherapy. The objective of this study was to compare the benefits and harms of LT4/LT3 combined therapy and LT4 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 quasiexperimental studies comparing combined therapy (LT4/LT3) versus monotherapy (LT4) 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 the 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 with 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 LT4/LT3 combined therapy and LT4 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. CRD42020202658.

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