Patient Preference for Levo-Triiodothyronine, Levothyroxine Combination Therapy vs Levothyroxine Alone

Model of thyroid gland surrounded by six blister packs with white pills inside in corners of image on orange background. Photo concept art of treatment or hormone replacement therapy of thyroid
Researchers assessed patient preference for combination L-T3/L-T4 treatment vs L-T4 monotherapy.

Approximately half of patients with hypothyroidism reported preferring combination therapy with levo-triiodothyronine (L-T3) and levothyroxine (L-T4) compared with L-T4 monotherapy, according to results of a systematic review and meta-analysis published in Frontiers in Endocrinology.

While the standard medical treatment for hypothyroidism is L-T4, patients with hypothyroidism are often not satisfied with their treatment. The goal of this study was to assess patient preference for combination L-T3/L-T4 treatment compared with L-T4 monotherapy.

Following a comprehensive search in 9 electronic databases for randomized controlled trials reporting how often patients with hypothyroidism prefer combination treatment to L-T4 monotherapy, published from inception until February 2019, two reviewers critically appraised the quality of the studies and abstracted the data.

The meta-analysis included 7 blinded randomized controlled trials with a total of 348 patients with hypothyroidism. In a random effects meta-analysis, approximately 46% (95% CI, 40.2%-52.4%) of adult patients with hypothyroidism preferred combination therapy with L-T3 and L-T4 over L-T4 monotherapy, with no significant difference relative to chance (P =.231).

In planned sensitivity analyses that aimed to assess potential differences in treatment benefits according to patient, study, or disease characteristics, preference of combination treatment was partially explained by treatment effects on thyroid-stimulating hormone levels. In addition, mood and symptoms of hypothyroidism may have affected patient preference, as several trials reporting improvement in mood and symptoms tended to report higher rates of combination therapy preference.

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Meta-regression performed to explore dose effect on treatment preference indicated a statistically significant positive association between the total daily dose of L-T3 (ranging between 0 and 20 µg/d; P =.020), but not with the L-T4:L-T3 ratio or treatment preference.

According to the researchers, the study had several limitations, including the small number of trials, short duration of the included trials, and exclusion of studies written in languages other than English.

“[A]lthough L-T4 monotherapy is the standard of care in management of hypothyroidism in adults, dissatisfaction among some patients treated with L-T4 as well as significant uncertainties relating to thyroid hormone alternatives, highlights the critical need for more research on effective treatments to optimize the well-being and treatment satisfaction in this population,” concluded the researchers.

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Akirov A, Fazelzad R, Ezzat S, Thabane L, Sawka AM. A systematic review and meta-analysis of patient preferences for combination thyroid hormone treatment for hypothyroidism [published online July 24, 2019]. Front Endocrinol. doi:10.3389/fendo.2019.00477