Short answer: Levothyroxine (Synthroid) is synthetic T4; liothyronine (Cytomel) is synthetic T3, the active hormone. T4 lasts about 6 to 7 days in the body; T3 about 2.5 days or less.12 Both labels carry a boxed warning: not for obesity or weight loss. The American Thyroid Association calls levothyroxine the standard of care.3
| Levothyroxine (Synthroid) | Liothyronine (Cytomel) | |
|---|---|---|
| Hormone | L-thyroxine (T4)1 | L-triiodothyronine (T3)2 |
| How it works | The body converts T4 to T3; about 80% of circulating T3 comes from T41 | Supplies the active hormone directly2 |
| Approved uses | Hypothyroidism; add-on in thyroid cancer care1 | Hypothyroidism; add-on in thyroid cancer care; diagnostic suppression test2 |
| Label dosing (adult hypothyroidism) | Full replacement 1.6 mcg/kg/day; some start lower; adjust by 12.5 to 25 mcg every 4 to 6 weeks1 | 25 mcg once daily to start; increase by 25 mcg every 1 to 2 weeks; usual 25 to 75 mcg daily2 |
| Half-life | 6 to 7 days (3 to 4 in hyperthyroidism, 9 to 10 in hypothyroidism)1 | About 2.5 days per the Cytomel label; 2 days or less per the Synthroid table21 |
| Onset | Peak effect may take 4 to 6 weeks1 | Within a few hours; maximum response in 2 to 3 days2 |
| Absorption | 40% to 80%; take on an empty stomach 30 to 60 minutes before breakfast1 | About 95% absorbed within 4 hours2 |
| Strengths | 12 strengths from 25 to 300 mcg1 | 5, 25 and 50 mcg2 |
| Boxed warning | Not for obesity or weight loss; large doses can cause serious toxicity1 | Same2 |
T4 binds tightly to blood proteins, which is why it lasts about 6 to 7 days and its full effect can take 4 to 6 weeks to show.1 That long half-life gives steady levels on once-daily dosing and makes a missed dose less noticeable. T3 binds less tightly, acts within hours and peaks in effect within 2 to 3 days.2 Faster on and off also means dose changes are felt sooner, which is why the Cytomel label allows increases every 1 to 2 weeks.2
The American Thyroid Association's 2014 guideline concluded that levothyroxine should remain the standard of care for hypothyroidism, and found no consistently strong evidence that combination T4 and T3, or thyroid extract, improves health outcomes over levothyroxine alone.3 Both labels warn about heart effects, including atrial fibrillation, in older people and those with heart disease, and advise starting below the full dose.12
Both labels say thyroid hormones should not be used to treat obesity or for weight loss. In people with normal thyroid function, normal replacement doses do not cause weight loss, and larger doses can cause serious or life-threatening toxicity, especially with stimulant appetite suppressants.12