CONTEXT: Levothyroxine (L-T4) monotherapy is the standard of care for the treatment of hypothyroidism. A minority of L-T4-treated patients remain symptomatic and report better outcomes with combination therapy that contains liothyronine (L-T3) or with desiccated thyroid extract (DTE). OBJECTIVE: This work aimed to assess patient preferences in the treatment of hypothyroidism. METHODS: A systematic review, meta-analysis, meta-regression, and network meta-analysis of randomized controlled trials (RCTs) comparing treatments for adults with hypothyroidism (L-T4 vs L-T4 + L-T3 or DTE). Searches were conducted in PubMed, Embase, and Cochrane databases up to April 10, 2024. Data extraction and quality assessment were independently performed by 4 researchers. RESULTS: Eleven RCTs (8 cross-over studies) with a total of 1135 patients were considered. Overall, 24% of patients preferred L-T4 vs 52% who preferred L-T4 + L-T3 or DTE
24% had no preference. The meta-analysis confirmed the preference for combination therapy over L-T4 monotherapy (relative risk [RR]: 2.20
95% CI, 1.38-3.52
P = .0009). Excluding 4 studies reduced the high heterogeneity (I2 = 81%) without affecting the results (RR: 1.97
95% CI, 1.52-2.54
P <
.00001
I2 = 24%). This preference profile remained when only crossover studies were considered (RR: 2.84
95% CI, 1.50-5.39
P <
.00001). Network meta-analysis confirmed the preference for DTE and L-T3 + L-T4 vs L-T4 alone. CONCLUSION: Patients with hypothyroidism prefer combination therapy (L-T3 + L-T4 or DTE) over L-T4 monotherapy. The strength of these findings justifies considering patient preferences in the setting of shared decision-making in the treatment of hypothyroidism.