Levothyroxine added to a low-calorie diet for adults with obesity and high‑normal or mildly elevated TSH

Effect of Levothyroxine as Adjuvant Therapy to a Hypocaloric Diet in the Treatment of Obesity: a Randomized Placebo-controlled Trial.

We are testing whether adding levothyroxine to a low‑calorie diet helps adults 25–60 with grade I–II obesity and mildly high or high‑normal TSH lose more weight and keep it off.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 286 (estimated)
• Ages: 25 Years to 60 Years
• Sex: All
• Sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud (Academic / other)
• Locations: 5 sites (Cadiz and 4 other locations)
• Trial ID: NCT07332273 on ClinicalTrials.gov

What this trial studies

This is a phase III, randomized, double‑blind, placebo‑controlled multicentre trial in Spain enrolling 286 adults aged 25–60 with BMI 30.0–39.9 kg/m² who either have subclinical hypothyroidism (TSH 5–10 mIU/L with normal peripheral hormones) or are euthyroid with TSH in the upper reference tertile. Participants are randomized 1:1, stratified by age, sex, and BMI, to receive levothyroxine 88 µg once daily or placebo alongside a hypocaloric diet. The trial is conducted at multiple hospitals in Andalusia and will follow participants to measure weight change and related metabolic outcomes. Standard safety monitoring will be performed to detect thyroid hormone–related effects.

Who should consider this trial

Good fit: Adults 25–60 years old with BMI 30.0–39.9 kg/m² who either have subclinical hypothyroidism (TSH 5–10 mIU/L with normal peripheral hormones) or are euthyroid with TSH in the highest tertile, and who are not diabetic or on prior thyroid treatment, are the intended candidates.

Not a fit: People with diabetes, prior thyroid disease or current levothyroxine use, those outside the specified age or BMI ranges, pregnant or breastfeeding women, or those unable to attend participating Spanish sites are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, adding levothyroxine could improve weight loss and reduce weight regain for people with obesity who have mildly elevated or high‑normal TSH.

How similar studies have performed: Observational studies link thyroid status to body weight, but randomized trials testing levothyroxine for weight loss are limited and have not shown consistent, definitive benefit.

Eligibility criteria

Inclusion Criteria:

* Adults 25-60 years of age.
* Obesity grade I-II: BMI 30.0-39.9 kg/m².
* Either subclinical hypothyroidism (TSH 5-10 mIU/L with normal peripheral hormones) or euthyroid with TSH in the highest tertile of the population reference range (no known thyroid disease).
* Able and willing to provide written informed consent.
* Women of childbearing potential: not pregnant or breastfeeding and using a highly effective contraception method (failure rate \<1%) per CTCG guidance (e.g., hormonal methods, IUD/IUS, sterilization, or dual barrier with spermicide).

Exclusion Criteria:

* Diabetes mellitus (HbA1c ≥6.5%, fasting glucose ≥126 mg/dL, or 2-h OGTT ≥200 mg/dL).
* Any prior thyroid disease (hyperthyroidism, overt hypothyroidism) or prior LT4 treatment.
* Current or recent (≤3 months) use of levothyroxine, hypoglycaemic agents, antibiotics, or regular probiotics/prebiotics.
* Active cancer or cancer within the last 5 years (except basal-cell carcinoma).
* Chronic liver disease with total bilirubin ≥2.0 mg/dL or AST \>3× ULN.
* Established cardiovascular disease (e.g., stroke, ischemic heart disease, peripheral artery disease).
* Atrial fibrillation or any arrhythmia history.
* Uncontrolled hypertension (\>160/100 mmHg) despite therapy (assessed by ABPM at screening).
* Any heart failure; resting HR \>85 bpm; eGFR \<60 mL/min.
* Known HIV, HBV, or HCV infection.
* Acute inflammatory disease or inflammatory bowel disease.
* Serious underlying disease that, in the investigator's judgment, could affect participation.
* Drug/alcohol abuse, life expectancy \<12 months, inability to follow the recommended diet or attend visits.
* Positive pregnancy test, pregnant, expecting pregnancy, or breastfeeding.
* Hypersensitivity to any component of the investigational product.
* Inability or unwillingness to provide informed consent.

Where this trial is running

Cadiz and 4 other locations

• Hospital Puerta del Mar — Cadiz, Spain (Not_yet_recruiting)
• Hospital Reina Sofía — Córdoba, Spain (Not_yet_recruiting)
• Hospital Universitario de Jaén — Jaén, Spain (Not_yet_recruiting)
• Hospital Universitario Virgen de la Victoria — Málaga, Spain (Recruiting)
• Hospital Clínico Universitario de Valladolid — Valladolid, Spain (Not_yet_recruiting)

Conditions Obesity