Metformin Does Not Suppress Serum Thyrotropin by Increasing Levothyroxine Absorption

Area of Science:

• Pharmacokinetics and Drug Interactions
• Endocrinology and Metabolism

Background:

• Levothyroxine (LT4) absorption can be impacted by various factors, including medications.
• Metformin's effect on LT4 absorption and subsequent thyroid-stimulating hormone (TSH) levels is not fully understood.

Purpose of the Study:

• To investigate the impact of metformin ingestion on the absorption of levothyroxine (LT4).
• To assess changes in serum total thyroxine (TT4) concentrations following LT4 administration before and after metformin use.

Main Methods:

• A modified FDA LT4 bioequivalence protocol was used in healthy, metformin-naïve volunteers.
• Serum TT4 concentrations were measured at various time points after a 600 μg oral LT4 dose.
• Measurements were taken before and after one week of daily metformin (850 mg three times daily) administration.

Main Results:

• No significant differences were observed in peak serum TT4 concentrations or the time to reach peak TT4.
• A trend towards a reduced area under the concentration-time curve (AUC) for TT4 was noted after metformin ingestion (p=0.09).

Conclusions:

• Concomitant metformin ingestion does not alter levothyroxine (LT4) absorption.
• The observed suppression of TSH in patients taking both metformin and LT4 likely involves mechanisms other than enhanced LT4 absorption.