Liquid or soft-gel levothyroxine vs tablet levothyroxine in athyreotic adults after total thyroidectomy: Systematic review and meta-analysis

Table 1 Characteristics of the included studies

Ref.	Study design	Follow-up (weeks)	n (total)	Female (%)	Age (years)	BMI	Thyroid-stimulating hormone baseline	Malabsorption	Disease
Brancato et al[24], 2014	Retrospective cohort	14	53	94.3	45	26.8	3.04	35.9%	Thyroiditis (66%), thyroidectomy (26%), goiter (8%)
Negro et al[25], 2014	Prospective cohort	54	200	81	53	-	1.71	None	Surgical (29%) or autoimmune (71%)
Vita et al[26], 2014	Prospective cohort	27	24	75	56.2	-	4.1	100%	Primary hypothyroidism (58%) or DTC (42%)
Cappelli et al[27], 2017	RCT	54	102	78.4	49.4	24.1	0.28	None	DTC
Fallahi et al[28], 2016	Prospective cohort	54	21	81	51	24.4	7.6	None	Autoimmune thyroiditis (62%), nodular goiter (38%)
Lombardi et al[29], 2017	RCT	10	155	84.5	51.5	26.4	8	None	Benign diseases only
Fallahi et al[30], 2018	Prospective cohort	15	105	77	48	24.5	2.55	None	Thyroid cancer only (papillary/follicular)
Baratta et al[31], 2025	RCT	10	130	100	51.6	26.4	8	None	Thyroidectomized patients
Gatta et al[32], 2025	Retrospective cohort	13	275	78.2	53	25.7	1.2	27.6%	DTC (28%) vs benign (72%)

BMI: Body mass index; RCT: Randomized controlled trial; DTC: Differentiated thyroid cancer.

Table 2 Certainty of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach

Outcomes	Anticipated absolute effects (95%CI)	n of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Liquid levothyroxine
Thyroid-stimulating hormone	SMD 0.91 lower (1.52 lower to 0.3 lower)	1115 (9 studies)	Lowa,b	Liquid levothyroxine may lead to a greater reduction in thyroid-stimulating hormone levels compared to tablet levothyroxine, but the evidence is uncertain
T4 levels	SMD 0.34 higher (0.15 higher to 0.52 higher)	480 (5 studies)	Moderatea	Liquid levothyroxine probably results in slightly higher circulating T4 levels compared to tablet levothyroxine
T3 levels	SMD 0.25 higher (0.06 higher to 0.44 higher)	432 (4 studies)	Moderatea	Liquid levothyroxine probably results in slightly higher T3 levels compared to tablet levothyroxine

^aMost included studies had a moderate risk of bias.

^bHigh heterogeneity found in analysis.

CI: Confidence interval; GRADE: Grades of Recommendation, Assessment, Development and Evaluation; SMD: Standardized mean differences; T4: Total thyroxine; T3: Triiodothyronine.