Millan-Alanis JM, et al. Thyroid. 2021;doi:10.1089/thy.2021.0270.

Disclosures: The authors report no relevant financial disclosures.
September 14, 2021
2 min read

Similar efficacy with levothyroxine monotherapy, combined therapy in hypothyroidism


Millan-Alanis JM, et al. Thyroid. 2021;doi:10.1089/thy.2021.0270.

Disclosures: The authors report no relevant financial disclosures.
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Combined levothyroxine and liothyronine therapy provides similar efficacy to levothyroxine monotherapy for adults with hypothyroidism, according to a systematic review and meta-analysis published in Thyroid.

“We believe that our findings have both clinical and research implications,” René Rodríguez-Gutiérrez, MD, MSc, PhD, assistant professor in the department of endocrinology, metabolism and diabetes at the Mayo Clinic, told Healio. “From a clinical standpoint, we reinforce previous evidence suggesting similar efficacy between monotherapy and combined therapy for hypothyroidism, as well as report high patient preferences for the latter. This information will provide more certainty for patients and clinicians looking for alternative therapies in patients that are unresponsive to monotherapy. From a research standpoint, our study helps in identifying significant gaps in the evidence regarding this topic that will need to be answered in the future.”

Thyroid anatomy 2019
Source: Adobe Stock.

Rodríguez-Gutiérrez and colleagues conducted a systematic review and meta-analysis of randomized controlled trials and quasi-experimental studies comparing the efficacy of levothyroxine and liothyronine combination therapy with levothyroxine monotherapy in adults with primary or central hypothyroidism. Researchers searched the PubMed, Scopus, Embase, Web of Science and Cochrane Central databases from inception until September 2020. Outcomes evaluated included treatment effect on clinical status, quality of life, psychological distress, depressive symptoms and fatigue.

The review included 18 trials with a combined 1,563 participants. The risk of bias was low for most studies. Clinical status, quality of life, psychological distress, depression and fatigue were all evaluated through clinical questionnaires, with no differences observed between combined therapy and monotherapy in any of the outcomes.

In subgroup analysis where participants were separated into a group with a duration of treatment 12 weeks or less and a group with a duration longer than 12 weeks, those who had a shorter duration of treatment favored levothyroxine monotherapy compared with combined therapy (standardized mean difference = 0.15; 95% CI, 0.02-0.28; P = .02). There was no significant difference for favoring combined therapy between the two groups, and no differences were observed for psychological distress and depressive symptoms. There was a tendency toward favoring combined therapy when doses of liothyronine were higher than 10 µg for change in depressive symptoms (standardized mean difference = –0.21; 95% CI, –0.41 to –0.01; P = .04).

Of 10 crossover trials, six asked for patient preferences after the study’s completion. Combination therapy was preferred for 43% of participants, 23% preferred monotherapy and 30% had no preference.

“We were surprised to observe that even when there was not an evident difference between both therapies regarding clinical outcomes, a higher proportion of participants did prefer combined therapy compared to monotherapy, according to our data analysis,” Rodríguez-Gutiérrez said. “We were only left with the hypothesis that either there was an extra factor that could have contributed to this preference, or that previous tools that have evaluated clinical outcomes in trials on patients with hypothyroidism are not fully adequate to evaluate the whole spectrum of treatment response.”

The researchers wrote that incidences of adverse events did not appear to differ with combined therapy compared with monotherapy. However, a statistical comparison was not done due to the heterogeneous form of reporting across studies.

“This paper could mainly concern patients with hypothyroidism who are unresponsive to levothyroxine monotherapy, for them and their clinicians to be aware of other treatment alternatives that are not only as beneficial for them, but also accompanied with high proportions of patient preferences,” Rodríguez-Gutiérrez said.

For more information:

René Rodríguez-Gutiérrez, MD, MSc, PhD, can be reached at