Liothyronine
Liothyronine is active T3. It has clinical replacement uses, mixed evidence for persistent thyroid symptoms and depression augmentation, and clear effects on energy metabolism. Those effects do not establish healthy cognitive enhancement or fat loss that preserves muscle.
Synthetic triiodothyronine sodium, or T3
- Liothyronine is T3; levothyroxine is T4 and is a separate compound.
- The label explicitly rejects obesity and weight-loss use.
- Selected fatigue and depression studies were positive; larger or blinded comparisons did not consistently replicate the benefit.
- Excess exposure can cause arrhythmia, ischemia, bone loss, and dangerous sympathomimetic interactions.
What is liothyronine approved to do?
Liothyronine is synthetic T3, the more immediately active thyroid hormone. US Cytomel is approved for thyroid replacement, adjunctive TSH suppression in selected differentiated thyroid cancer, and selected diagnostic suppression. Obesity, weight loss, and bodybuilding are outside the indication and inside the boxed warning.
US Cytomel label · T3 indications, PK, boxed warning
FDA prescribing information
Pfizer Laboratories Div Pfizer Inc. CYTOMEL (liothyronine sodium) tablets. DailyMed setid 51452b31-ff68-4e0c-b982-c15502ebf1d3. Revised April 2025; record updated May 18, 2026.
The US label covers thyroid-hormone replacement, adjunctive TSH suppression in well-differentiated thyroid cancer, and selected diagnostic suppression testing. It carries a boxed warning against obesity or weight-loss use, reports about 95% absorption within four hours and a biological half-life around 2.5 days, and details cardiovascular, bone, adrenal, glycemic, anticoagulant, digoxin, antidepressant, and sympathomimetic risks.
- Participants / model
- Patients with labeled hypothyroid, thyroid-cancer suppression, or diagnostic indications
- Treatment
- Oral liothyronine sodium tablets
- Follow-up
- Current product record; initial US approval 1956
- Study design
- Regulatory prescribing information
The 2.5-day value is described as a biological half-life, not a formulation-independent terminal plasma half-life, and the label supplies no clean Tmax.
Read the original sourcePubChem CID 5920 · T3 identity
Government substance database
National Library of Medicine. PubChem Compound Summary for CID 5920, Liothyronine.
Identifies liothyronine/T3 base as C15H12I3NO4, molecular weight 650.97 g/mol, CID 5920.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Living database record
- Study design
- Curated chemical identity record
Liothyronine base and liothyronine sodium formulations are distinct chemical records; T3 is not an alias for T4.
Read the original sourceDoes replacing T4 with T3 improve symptoms or performance?
In a four-month trial, 46 stable patients were randomized and 44 analyzed. Adding T3 did not improve weight, lipids, heart rate, blood pressure, hypothyroid quality of life, or 12 of 13 cognitive tests; the remaining pegboard result favored T4 alone. A crossover randomized 18 and was completed by 14: at matched TSH, T3 lowered weight by 1.8 kg within person and lowered several lipids, while fat mass, fat-free mass, bone density, exercise tolerance, heart rate, blood pressure, and insulin sensitivity were unchanged.
| Study | Result | Limit |
|---|---|---|
| 46 randomized; 44 analyzed; 4 months | Combination no better on weight, lipids, quality of life, or 12/13 cognitive tests | Selected stable patients at one military facility; one combination withdrawal for tremor/fatigue |
| 18 randomized; 14 completed crossover | Within-person weight −1.8 kg on T3; total cholesterol, LDL, and apoB lower | Tiny selected inpatient replacement study; fat mass, exercise, cardiovascular measures, and insulin sensitivity unchanged |
46 hypothyroid patients · combination therapy null
Randomized double-blind placebo-controlled trial
Patrick W. Clyde, Amir E. Harari, Eric J. Getka, and K. M. Mohamed Shakir. JAMA. 2003. PMID 14665656.
Forty-six were randomized and 44 analyzed. Hypothyroid quality-of-life scores improved in both groups but did not differ (p=0.54); body weight, lipids, heart rate, and blood pressure were unchanged. Twelve of 13 cognitive tests were null and the remaining pegboard test favored levothyroxine alone.
- Participants / model
- 46 adults with primary hypothyroidism randomized; 44 analyzed
- Treatment
- Levothyroxine/liothyronine combination versus continued levothyroxine
- Follow-up
- 4 months
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- National Naval Medical Center institutional support
Single military facility, selected stable patients, self-reported adherence without pill counts, and one combination strategy. One combination participant withdrew with tremor, fatigue, and work impairment despite normal laboratory values.
Read the original source14 hypothyroid patients · metabolic differences under replacement
Randomized double-blind crossover trial
Francesco S. Celi, Marina Zemskova, Joyce D. Linderman, et al. Journal of Clinical Endocrinology & Metabolism. 2011. PMID 21865366.
Eighteen were randomized and 14 completed. At matched TSH, within-person weight was 1.8±1.9 kg lower on T3 (p=0.009); total cholesterol, LDL, and apoB were lower. Fat mass, fat-free mass, bone density, resting energy expenditure, exercise, heart rate, blood pressure, and insulin sensitivity did not differ.
- Participants / model
- 18 adults with hypothyroidism randomized; 14 completed the crossover; 13 women and one man among completers
- Treatment
- Liothyronine versus levothyroxine replacement
- Follow-up
- At least 6 weeks stable at target before each inpatient assessment
- Study design
- Randomized double-blind crossover trial
- Funding
- Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Highly selected inpatient assessments after stable replacement; cardiovascular disease, hypertension, and diabetes were excluded. The trial is too small for uncommon harms and says nothing about euthyroid weight loss.
Read the original sourceCan T3 help people who still feel unwell on T4?
Some selected symptomatic patients report better fatigue and cognitive symptoms on T3. Blinded whole-group comparisons are less consistent, and treatment preference alone does not establish superiority.
In a nonblinded crossover, 59 women entered and 47 completed. T3 lowered total fatigue by 4.4 points, ThyPRO tiredness by 15 and cognitive complaints by nine versus T4. Five symptom-related withdrawals occurred on T3 versus one on T4. Resting heart rate and blood pressure did not differ; that short observation does not settle long-term safety.
A 2025 trial randomized 158 and analyzed 151; two quality-of-life subscales favored combination treatment, but overall physical and mental summary scores and weight were neutral. A postsurgical feasibility trial analyzed only 12 people and found no significant weight, lipid or quality-of-life advantage.
Earlier blinded comparisons also found differences between whole-group results and selected symptomatic subgroups. A prespecified responder rule still needs validation.
Bjerkreim et al., symptomatic women on T3 versus T4
Randomized controlled human trial
Bjerkreim BA, Hammerstad SS, Gulseth HL, Berg TJ, Omdal LJ, Lee-Ødegård S, Eriksen EF. Effect of Liothyronine Treatment on Quality of Life in Female Hypothyroid Patients With Residual Symptoms on Levothyroxine Therapy: A Randomized Crossover Study. Frontiers in endocrinology. 2022. DOI 10.3389/fendo.2022.816566.
Fifty-nine women with persistent symptoms entered nonblinded 12-week crossover periods; 47 completed. Compared with T4, T3 reduced total-fatigue score by 4.4 points, ThyPRO tiredness by 15 and cognitive complaints by 9. These are between-treatment differences, unlike larger baseline changes quoted in the abstract. Five symptom-related withdrawals occurred on T3 versus one on T4. Resting BP/HR did not differ, but the selected sample, subjective outcomes, lack of blinding and attrition limit certainty. It is not a healthy-user cognitive trial.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
2025 Iranian T4/T3 randomized trial
Randomized controlled human trial
Hajtalebi F, Alaei-Shahmiri F, Golgiri F, Shahini N, Akbari H, Assadian K, Mosalamiaghili S. Early effects of LT3 + LT4 combination therapy on quality of life in hypothyroid patients: a randomized, double-blind, parallel-group comparison trial. BMC endocrine disorders. 2025. DOI 10.1186/s12902-025-01840-4.
The full report gives 158 randomized and 151 analyzed, with all seven withdrawals in the combination arm. At six months two SF-36 subscales favored combination treatment; physical/mental summary comparisons were null and weight did not improve. Several tabulated intervals and registration dates are internally inconsistent. The result differed by endpoint.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
Phan et al., 2025 total-thyroidectomy feasibility study
Primary human study
Phan et al., 2025 total-thyroidectomy feasibility study. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1522753/full
Thirteen randomized participants, 12 analyzed, compared T4 with T4/T3 following total thyroidectomy. T3 concentrations differed, but weight, lipids and quality-of-life differences were nonsignificant. The small exploratory study used no multiplicity adjustment and last-observation carry-forward; blood draws near T3 peaks and inability to adjust T3 independently complicate interpretation. It supports a larger study, not a demonstrated clinical win.
Read the original source141 patients · preference signal tracked lower TSH and weight
Randomized double-blind controlled trial
Bente C. Appelhof, Eric Fliers, Ellie M. Wekking, et al. Journal of Clinical Endocrinology & Metabolism. 2005. PMID 15705921.
Of 141 randomized, 140 entered intention-to-treat analysis and 130 completed. Preference was 29.2%, 41.3%, and 52.2% across T4, 10:1, and 5:1 groups (trend p=0.024), while mood, fatigue, wellbeing, and cognition did not differ. The 5:1 arm ended at median TSH 0.07, pulse +3.9 beats/min, and weight −1.7 kg.
- Participants / model
- 141 adults with primary autoimmune hypothyroidism stable on levothyroxine
- Treatment
- Levothyroxine alone or two levothyroxine/liothyronine ratios
- Follow-up
- 15 weeks
- Study design
- Double-blind randomized controlled comparative trial
The highest-T3 arm was commonly biochemically over-replaced; 44% of combination-preferrers had TSH below 0.11. Seven withdrew for side effects, and one 5:1 participant developed recurrent atrial ectopy. Multiple outcomes were tested.
Read the original sourceThree-way crossover · 75 completers, whole-group null
Prospective randomized double-blind three-period crossover trial
K. M. Mohamed Shakir, David I. Brooks, Elizabeth A. McAninch, et al. Journal of Clinical Endocrinology & Metabolism. 2021;106(11):e4400 to e4413. PMID 34185829.
Ninety enrolled and 75 completed all three 22-week periods. Whole-group thyroid symptoms, general health, depression, memory, weight, lipids, and preference did not differ among T4, T4/T3, and desiccated thyroid; the latter raised heart rate by 2.2 beats/min. A most-symptomatic-third analysis was post hoc.
- Participants / model
- 90 military-health-system beneficiaries aged 18 to 65 with primary hypothyroidism; 75 completed; 77% women and 77% White among completers
- Treatment
- Levothyroxine, levothyroxine/liothyronine, and desiccated thyroid in randomized crossover order with TSH adjustment
- Follow-up
- Three 22-week treatment periods
- Study design
- Prospective randomized double-blind three-period crossover trial
- Funding
- Walter Reed National Military Medical Center Institutional Research Board
Fifteen withdrew before randomization because of relocation or time constraints. Cardiac disease and several common comorbidities/medications were excluded. The symptomatic-third result was post hoc and vulnerable to regression to the mean.
Read the original sourceDoes T3 help antidepressants work?
One randomized trial was positive, a larger trial did not replicate it, and STAR*D provided an active-comparator result. The evidence supports selected clinical use, not a reliable benefit for every patient or a healthy mood boost.
In 124 adults with major depression, eight weeks of sertraline plus T3 produced response rates of 70% versus 50% and remission rates of 58% versus 38% with sertraline plus placebo. Treatment began together, so this was not necessarily rescue after an adequate failed course.
A later blinded 153-person trial found no advantage: response was 61.8% versus 65%, and remission 40.8% versus 50.6%. Sertraline schedules differed between the trials. STAR*D compared T3 with lithium without a placebo arm; its 24.7% versus 15.9% remission difference was nonsignificant. These are conflicting results, not an absence of research.
Cooper-Kazaz et al., sertraline plus T3 randomized trial
Randomized controlled human trial
Cooper-Kazaz R, Apter JT, Cohen R, Karagichev L, Muhammed-Moussa S, Grupper D, Drori T, Newman ME, Sackeim HA, Glaser B, Lerer B. Combined treatment with sertraline and liothyronine in major depression: a randomized, double-blind, placebo-controlled trial. Archives of general psychiatry. 2007. DOI 10.1001/archpsyc.64.6.679.
In 124 adults with major depression, eight-week double-blind treatment produced response rates of 70% versus 50% and remission rates of 58% versus 38% for sertraline-plus-T3 versus sertraline-plus-placebo. It studied concurrent initiation, not necessarily rescue after failed adequate treatment; sertraline dosing and remission definitions matter when comparing later trials. It found no significant overall adverse-effect-frequency difference, but eight weeks cannot establish long-term cardiac/bone safety.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
Garlow et al., 153-person sertraline augmentation trial
Randomized controlled human trial
Garlow SJ, Dunlop BW, Ninan PT, Nemeroff CB. The combination of triiodothyronine (T3) and sertraline is not superior to sertraline monotherapy in the treatment of major depressive disorder. Journal of psychiatric research. 2012. DOI 10.1016/j.jpsychires.2012.08.009.
A later eight-week randomized blinded trial found no T3 advantage: response was 61.8% with T3 versus 65% with placebo, and remission 40.8% versus 50.6%. Sertraline was flexibly dosed, averaging about 145 mg at final assessment, unlike the earlier fixed schedule. This is important nonreplication, not proof that the earlier trial was fabricated or that no subgroup can benefit.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
STAR*D step 3 · active comparison, no placebo
Randomized open-label active-comparator effectiveness trial
Andrew A. Nierenberg, Maurizio Fava, Madhukar H. Trivedi, et al. American Journal of Psychiatry. 2006. PMID 16946176.
Among 142 adults with major depression after two unsuccessful medication steps, remission was 24.7% with T3 augmentation and 15.9% with lithium, a nonsignificant difference. Fewer T3 participants discontinued because of side effects.
- Participants / model
- 142 adult outpatients with nonpsychotic major depression after two failed or intolerable prospective medication steps
- Treatment
- Liothyronine augmentation versus lithium augmentation
- Follow-up
- Up to 14 weeks; mean treatment 9.6 weeks
- Study design
- Randomized open-label active-comparator effectiveness trial
STAR*D level 3 included only patients willing to accept the listed options, used an open-label active comparison, and had no placebo.
Read the original sourceDoes T3 reverse metabolic slowdown or spare muscle while cutting?
T3 changes human energy metabolism. The studies do not establish durable fat-loss benefit with muscle preservation, and some directly suggest increased protein breakdown.
Nine inpatients were studied before and after 10% dietary weight loss. Five-week T3/placebo periods reversed selected changes in muscle efficiency and gene expression. Weight was controlled; the experiment did not test long-term prevention of weight regain.
In seven normal adults, seven days of slightly supraphysiological T3 increased leucine carbon and nitrogen flux, consistent with greater protein degradation. An older severe-diet-restriction study found faster weight loss and increased urinary nitrogen; the authors attributed the extra loss to lean tissue.
The small T3-versus-T4 replacement crossover found about 1.8 kg lower weight on T3, but its fat-mass comparison was nonsignificant. Changes in scale weight, adaptive physiology and useful body composition are separate outcomes.
Rosenbaum et al., T3 repletion after dietary weight loss
Randomized controlled human trial
Rosenbaum M, Goldsmith RL, Haddad F, Baldwin KM, Smiley R, Gallagher D, Leibel RL. Triiodothyronine and leptin repletion in humans similarly reverse weight-loss-induced changes in skeletal muscle. American journal of physiology. Endocrinology and metabolism. 2018. DOI 10.1152/ajpendo.00116.2018.
Nine inpatients with obesity were examined at usual weight and after 10% dietary weight loss, with five-week placebo/T3 crossover periods. T3 reversed selected changes in skeletal-muscle efficiency and myosin/SERCA expression. This is a mechanistic test of adaptive physiology; weight was controlled, and it was not a durable weight-regain-prevention trial. The leptin comparator data came from a different, partly previously reported population.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
Primary abstract and metadata
Read the original sourceHuman leucine-flux experiment in normal adults
Primary human study
Tsalikian E, Lim VS. L-triiodothyronine at a slightly over physiologic dose increases leucine flux, which suggests an increase in protein degradation in normal subjects. The Journal of laboratory and clinical medicine. 1989. PMID 2754304.
Seven normal adults received a seven-day T3 exposure producing slightly supraphysiological concentrations. Leucine carbon and nitrogen flux increased in the postabsorptive state, consistent with increased protein degradation. There was no large randomized body-composition trial here, but it directly challenges the assumption that thyroid-driven weight reduction is muscle-sparing.
Primary abstract and metadata
Read the original sourceT3, weight loss and nitrogen excretion during severe restriction
Primary human study
Wolman SI, Sheppard H, Fern M, Waterlow JC. The effect of tri-iodothyronine (T3) on protein turnover and metabolic rate. International journal of obesity. 1985. PMID 3830937.
In patients with obesity losing weight slowly under marked energy restriction, short T3 treatment accelerated weight loss and increased urinary nitrogen; changes in basal metabolic rate and protein turnover were not significant. Authors attributed the extra loss to lean tissue. The restrictive-diet context prevents direct extrapolation to every regimen, but the study shows why scale weight alone is an inadequate benefit endpoint.
The abstract does not report sample size or full methods.
Read the original source14 hypothyroid patients · metabolic differences under replacement
Randomized double-blind crossover trial
Francesco S. Celi, Marina Zemskova, Joyce D. Linderman, et al. Journal of Clinical Endocrinology & Metabolism. 2011. PMID 21865366.
Eighteen were randomized and 14 completed. At matched TSH, within-person weight was 1.8±1.9 kg lower on T3 (p=0.009); total cholesterol, LDL, and apoB were lower. Fat mass, fat-free mass, bone density, resting energy expenditure, exercise, heart rate, blood pressure, and insulin sensitivity did not differ.
- Participants / model
- 18 adults with hypothyroidism randomized; 14 completed the crossover; 13 women and one man among completers
- Treatment
- Liothyronine versus levothyroxine replacement
- Follow-up
- At least 6 weeks stable at target before each inpatient assessment
- Study design
- Randomized double-blind crossover trial
- Funding
- Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Highly selected inpatient assessments after stable replacement; cardiovascular disease, hypertension, and diabetes were excluded. The trial is too small for uncommon harms and says nothing about euthyroid weight loss.
Read the original sourceIs the often-quoted T3 half-life a precise plasma value?
Cytomel reports about 95 percent absorption within four hours and a biological half-life around 2.5 days. The label gives no clean oral Tmax. Peaks, troughs, thyroid status, binding proteins, and formulation all change the concentration-time pattern.
US Cytomel label · T3 indications, PK, boxed warning
FDA prescribing information
Pfizer Laboratories Div Pfizer Inc. CYTOMEL (liothyronine sodium) tablets. DailyMed setid 51452b31-ff68-4e0c-b982-c15502ebf1d3. Revised April 2025; record updated May 18, 2026.
The US label covers thyroid-hormone replacement, adjunctive TSH suppression in well-differentiated thyroid cancer, and selected diagnostic suppression testing. It carries a boxed warning against obesity or weight-loss use, reports about 95% absorption within four hours and a biological half-life around 2.5 days, and details cardiovascular, bone, adrenal, glycemic, anticoagulant, digoxin, antidepressant, and sympathomimetic risks.
- Participants / model
- Patients with labeled hypothyroid, thyroid-cancer suppression, or diagnostic indications
- Treatment
- Oral liothyronine sodium tablets
- Follow-up
- Current product record; initial US approval 1956
- Study design
- Regulatory prescribing information
The 2.5-day value is described as a biological half-life, not a formulation-independent terminal plasma half-life, and the label supplies no clean Tmax.
Read the original sourceWhy is excess T3 more than feeling wired?
Over-replacement can trigger angina, arrhythmia, myocardial infarction, bone loss, heat intolerance, muscle wasting, and worsening glucose control. Correct adrenal insufficiency first. Anticoagulants, diabetes medicines, digoxin, tricyclic or tetracyclic antidepressants, and sympathomimetics can require clinical adjustment; the boxed warning specifically flags life-threatening toxicity with sympathomimetic co-use.
US Cytomel label · T3 indications, PK, boxed warning
FDA prescribing information
Pfizer Laboratories Div Pfizer Inc. CYTOMEL (liothyronine sodium) tablets. DailyMed setid 51452b31-ff68-4e0c-b982-c15502ebf1d3. Revised April 2025; record updated May 18, 2026.
The US label covers thyroid-hormone replacement, adjunctive TSH suppression in well-differentiated thyroid cancer, and selected diagnostic suppression testing. It carries a boxed warning against obesity or weight-loss use, reports about 95% absorption within four hours and a biological half-life around 2.5 days, and details cardiovascular, bone, adrenal, glycemic, anticoagulant, digoxin, antidepressant, and sympathomimetic risks.
- Participants / model
- Patients with labeled hypothyroid, thyroid-cancer suppression, or diagnostic indications
- Treatment
- Oral liothyronine sodium tablets
- Follow-up
- Current product record; initial US approval 1956
- Study design
- Regulatory prescribing information
The 2.5-day value is described as a biological half-life, not a formulation-independent terminal plasma half-life, and the label supplies no clean Tmax.
Read the original sourceStudies and sources
US Cytomel label · T3 indications, PK, boxed warning
FDA prescribing information
Pfizer Laboratories Div Pfizer Inc. CYTOMEL (liothyronine sodium) tablets. DailyMed setid 51452b31-ff68-4e0c-b982-c15502ebf1d3. Revised April 2025; record updated May 18, 2026.
The US label covers thyroid-hormone replacement, adjunctive TSH suppression in well-differentiated thyroid cancer, and selected diagnostic suppression testing. It carries a boxed warning against obesity or weight-loss use, reports about 95% absorption within four hours and a biological half-life around 2.5 days, and details cardiovascular, bone, adrenal, glycemic, anticoagulant, digoxin, antidepressant, and sympathomimetic risks.
- Participants / model
- Patients with labeled hypothyroid, thyroid-cancer suppression, or diagnostic indications
- Treatment
- Oral liothyronine sodium tablets
- Follow-up
- Current product record; initial US approval 1956
- Study design
- Regulatory prescribing information
The 2.5-day value is described as a biological half-life, not a formulation-independent terminal plasma half-life, and the label supplies no clean Tmax.
Read the original source46 hypothyroid patients · combination therapy null
Randomized double-blind placebo-controlled trial
Patrick W. Clyde, Amir E. Harari, Eric J. Getka, and K. M. Mohamed Shakir. JAMA. 2003. PMID 14665656.
Forty-six were randomized and 44 analyzed. Hypothyroid quality-of-life scores improved in both groups but did not differ (p=0.54); body weight, lipids, heart rate, and blood pressure were unchanged. Twelve of 13 cognitive tests were null and the remaining pegboard test favored levothyroxine alone.
- Participants / model
- 46 adults with primary hypothyroidism randomized; 44 analyzed
- Treatment
- Levothyroxine/liothyronine combination versus continued levothyroxine
- Follow-up
- 4 months
- Study design
- Randomized double-blind placebo-controlled trial
- Funding
- National Naval Medical Center institutional support
Single military facility, selected stable patients, self-reported adherence without pill counts, and one combination strategy. One combination participant withdrew with tremor, fatigue, and work impairment despite normal laboratory values.
Read the original source14 hypothyroid patients · metabolic differences under replacement
Randomized double-blind crossover trial
Francesco S. Celi, Marina Zemskova, Joyce D. Linderman, et al. Journal of Clinical Endocrinology & Metabolism. 2011. PMID 21865366.
Eighteen were randomized and 14 completed. At matched TSH, within-person weight was 1.8±1.9 kg lower on T3 (p=0.009); total cholesterol, LDL, and apoB were lower. Fat mass, fat-free mass, bone density, resting energy expenditure, exercise, heart rate, blood pressure, and insulin sensitivity did not differ.
- Participants / model
- 18 adults with hypothyroidism randomized; 14 completed the crossover; 13 women and one man among completers
- Treatment
- Liothyronine versus levothyroxine replacement
- Follow-up
- At least 6 weeks stable at target before each inpatient assessment
- Study design
- Randomized double-blind crossover trial
- Funding
- Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH
Highly selected inpatient assessments after stable replacement; cardiovascular disease, hypertension, and diabetes were excluded. The trial is too small for uncommon harms and says nothing about euthyroid weight loss.
Read the original source141 patients · preference signal tracked lower TSH and weight
Randomized double-blind controlled trial
Bente C. Appelhof, Eric Fliers, Ellie M. Wekking, et al. Journal of Clinical Endocrinology & Metabolism. 2005. PMID 15705921.
Of 141 randomized, 140 entered intention-to-treat analysis and 130 completed. Preference was 29.2%, 41.3%, and 52.2% across T4, 10:1, and 5:1 groups (trend p=0.024), while mood, fatigue, wellbeing, and cognition did not differ. The 5:1 arm ended at median TSH 0.07, pulse +3.9 beats/min, and weight −1.7 kg.
- Participants / model
- 141 adults with primary autoimmune hypothyroidism stable on levothyroxine
- Treatment
- Levothyroxine alone or two levothyroxine/liothyronine ratios
- Follow-up
- 15 weeks
- Study design
- Double-blind randomized controlled comparative trial
The highest-T3 arm was commonly biochemically over-replaced; 44% of combination-preferrers had TSH below 0.11. Seven withdrew for side effects, and one 5:1 participant developed recurrent atrial ectopy. Multiple outcomes were tested.
Read the original sourceSTAR*D step 3 · active comparison, no placebo
Randomized open-label active-comparator effectiveness trial
Andrew A. Nierenberg, Maurizio Fava, Madhukar H. Trivedi, et al. American Journal of Psychiatry. 2006. PMID 16946176.
Among 142 adults with major depression after two unsuccessful medication steps, remission was 24.7% with T3 augmentation and 15.9% with lithium, a nonsignificant difference. Fewer T3 participants discontinued because of side effects.
- Participants / model
- 142 adult outpatients with nonpsychotic major depression after two failed or intolerable prospective medication steps
- Treatment
- Liothyronine augmentation versus lithium augmentation
- Follow-up
- Up to 14 weeks; mean treatment 9.6 weeks
- Study design
- Randomized open-label active-comparator effectiveness trial
STAR*D level 3 included only patients willing to accept the listed options, used an open-label active comparison, and had no placebo.
Read the original sourceRussian study · T3-induced thyrotoxicosis in rats
Russian preclinical animal study
V. I. Sobolev. Ученые записки Крымского федерального университета имени В. И. Вернадского. Биология. Химия. 2016;2(68)(2):58 to 69.
The study used daily subcutaneous T3 to create graded experimental hyperthyroidism or thyrotoxicosis, then measured muscle M-responses to adrenaline. Reported systemic changes included higher heart rate, oxygen consumption, and progressive body-mass loss with more prolonged exposure.
- Participants / model
- Adult male white rats; abstract says 130 while methods account for 170 across five groups
- Treatment
- Subcutaneous triiodothyronine with acute intramuscular adrenaline testing
- Follow-up
- T3 for 4 or 10 days across study subgroups
- Study design
- Controlled in-situ preclinical physiology experiment
The abstract and methods report conflicting denominators. This induced-thyrotoxicosis rat study provides hazard and mechanism evidence, not human weight-loss efficacy.
Read the original sourcePubChem CID 5920 · T3 identity
Government substance database
National Library of Medicine. PubChem Compound Summary for CID 5920, Liothyronine.
Identifies liothyronine/T3 base as C15H12I3NO4, molecular weight 650.97 g/mol, CID 5920.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Living database record
- Study design
- Curated chemical identity record
Liothyronine base and liothyronine sodium formulations are distinct chemical records; T3 is not an alias for T4.
Read the original sourceThree-way crossover · 75 completers, whole-group null
Prospective randomized double-blind three-period crossover trial
K. M. Mohamed Shakir, David I. Brooks, Elizabeth A. McAninch, et al. Journal of Clinical Endocrinology & Metabolism. 2021;106(11):e4400 to e4413. PMID 34185829.
Ninety enrolled and 75 completed all three 22-week periods. Whole-group thyroid symptoms, general health, depression, memory, weight, lipids, and preference did not differ among T4, T4/T3, and desiccated thyroid; the latter raised heart rate by 2.2 beats/min. A most-symptomatic-third analysis was post hoc.
- Participants / model
- 90 military-health-system beneficiaries aged 18 to 65 with primary hypothyroidism; 75 completed; 77% women and 77% White among completers
- Treatment
- Levothyroxine, levothyroxine/liothyronine, and desiccated thyroid in randomized crossover order with TSH adjustment
- Follow-up
- Three 22-week treatment periods
- Study design
- Prospective randomized double-blind three-period crossover trial
- Funding
- Walter Reed National Military Medical Center Institutional Research Board
Fifteen withdrew before randomization because of relocation or time constraints. Cardiac disease and several common comorbidities/medications were excluded. The symptomatic-third result was post hoc and vulnerable to regression to the mean.
Read the original sourceCooper-Kazaz et al., sertraline plus T3 randomized trial
Randomized controlled human trial
Cooper-Kazaz R, Apter JT, Cohen R, Karagichev L, Muhammed-Moussa S, Grupper D, Drori T, Newman ME, Sackeim HA, Glaser B, Lerer B. Combined treatment with sertraline and liothyronine in major depression: a randomized, double-blind, placebo-controlled trial. Archives of general psychiatry. 2007. DOI 10.1001/archpsyc.64.6.679.
In 124 adults with major depression, eight-week double-blind treatment produced response rates of 70% versus 50% and remission rates of 58% versus 38% for sertraline-plus-T3 versus sertraline-plus-placebo. It studied concurrent initiation, not necessarily rescue after failed adequate treatment; sertraline dosing and remission definitions matter when comparing later trials. It found no significant overall adverse-effect-frequency difference, but eight weeks cannot establish long-term cardiac/bone safety.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
Garlow et al., 153-person sertraline augmentation trial
Randomized controlled human trial
Garlow SJ, Dunlop BW, Ninan PT, Nemeroff CB. The combination of triiodothyronine (T3) and sertraline is not superior to sertraline monotherapy in the treatment of major depressive disorder. Journal of psychiatric research. 2012. DOI 10.1016/j.jpsychires.2012.08.009.
A later eight-week randomized blinded trial found no T3 advantage: response was 61.8% with T3 versus 65% with placebo, and remission 40.8% versus 50.6%. Sertraline was flexibly dosed, averaging about 145 mg at final assessment, unlike the earlier fixed schedule. This is important nonreplication, not proof that the earlier trial was fabricated or that no subgroup can benefit.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
Bjerkreim et al., symptomatic women on T3 versus T4
Randomized controlled human trial
Bjerkreim BA, Hammerstad SS, Gulseth HL, Berg TJ, Omdal LJ, Lee-Ødegård S, Eriksen EF. Effect of Liothyronine Treatment on Quality of Life in Female Hypothyroid Patients With Residual Symptoms on Levothyroxine Therapy: A Randomized Crossover Study. Frontiers in endocrinology. 2022. DOI 10.3389/fendo.2022.816566.
Fifty-nine women with persistent symptoms entered nonblinded 12-week crossover periods; 47 completed. Compared with T4, T3 reduced total-fatigue score by 4.4 points, ThyPRO tiredness by 15 and cognitive complaints by 9. These are between-treatment differences, unlike larger baseline changes quoted in the abstract. Five symptom-related withdrawals occurred on T3 versus one on T4. Resting BP/HR did not differ, but the selected sample, subjective outcomes, lack of blinding and attrition limit certainty. It is not a healthy-user cognitive trial.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
2025 Iranian T4/T3 randomized trial
Randomized controlled human trial
Hajtalebi F, Alaei-Shahmiri F, Golgiri F, Shahini N, Akbari H, Assadian K, Mosalamiaghili S. Early effects of LT3 + LT4 combination therapy on quality of life in hypothyroid patients: a randomized, double-blind, parallel-group comparison trial. BMC endocrine disorders. 2025. DOI 10.1186/s12902-025-01840-4.
The full report gives 158 randomized and 151 analyzed, with all seven withdrawals in the combination arm. At six months two SF-36 subscales favored combination treatment; physical/mental summary comparisons were null and weight did not improve. Several tabulated intervals and registration dates are internally inconsistent. The result differed by endpoint.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
Phan et al., 2025 total-thyroidectomy feasibility study
Primary human study
Phan et al., 2025 total-thyroidectomy feasibility study. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1522753/full
Thirteen randomized participants, 12 analyzed, compared T4 with T4/T3 following total thyroidectomy. T3 concentrations differed, but weight, lipids and quality-of-life differences were nonsignificant. The small exploratory study used no multiplicity adjustment and last-observation carry-forward; blood draws near T3 peaks and inability to adjust T3 independently complicate interpretation. It supports a larger study, not a demonstrated clinical win.
Read the original sourceRosenbaum et al., T3 repletion after dietary weight loss
Randomized controlled human trial
Rosenbaum M, Goldsmith RL, Haddad F, Baldwin KM, Smiley R, Gallagher D, Leibel RL. Triiodothyronine and leptin repletion in humans similarly reverse weight-loss-induced changes in skeletal muscle. American journal of physiology. Endocrinology and metabolism. 2018. DOI 10.1152/ajpendo.00116.2018.
Nine inpatients with obesity were examined at usual weight and after 10% dietary weight loss, with five-week placebo/T3 crossover periods. T3 reversed selected changes in skeletal-muscle efficiency and myosin/SERCA expression. This is a mechanistic test of adaptive physiology; weight was controlled, and it was not a durable weight-regain-prevention trial. The leptin comparator data came from a different, partly previously reported population.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
Primary abstract and metadata
Read the original sourceHuman leucine-flux experiment in normal adults
Primary human study
Tsalikian E, Lim VS. L-triiodothyronine at a slightly over physiologic dose increases leucine flux, which suggests an increase in protein degradation in normal subjects. The Journal of laboratory and clinical medicine. 1989. PMID 2754304.
Seven normal adults received a seven-day T3 exposure producing slightly supraphysiological concentrations. Leucine carbon and nitrogen flux increased in the postabsorptive state, consistent with increased protein degradation. There was no large randomized body-composition trial here, but it directly challenges the assumption that thyroid-driven weight reduction is muscle-sparing.
Primary abstract and metadata
Read the original sourceT3, weight loss and nitrogen excretion during severe restriction
Primary human study
Wolman SI, Sheppard H, Fern M, Waterlow JC. The effect of tri-iodothyronine (T3) on protein turnover and metabolic rate. International journal of obesity. 1985. PMID 3830937.
In patients with obesity losing weight slowly under marked energy restriction, short T3 treatment accelerated weight loss and increased urinary nitrogen; changes in basal metabolic rate and protein turnover were not significant. Authors attributed the extra loss to lean tissue. The restrictive-diet context prevents direct extrapolation to every regimen, but the study shows why scale weight alone is an inadequate benefit endpoint.
The abstract does not report sample size or full methods.
Read the original sourceWhy is Liothyronine in A tier?
A for thyroid-hormone treatment in the appropriate clinical setting. Fatigue and depression trials include positive results and failed replication. Faster weight loss can include muscle; healthy enhancement does not inherit the clinical grade.