The biguanide metformin, widely used in the treatment of type 2 diabetes, was associated with a 55% increased risk of low thyroid-stimulating hormone (TSH) levels in patients with hypothyroidism when compared with sulfonylurea use. The research, reported in Canadian Medical Association Journal (CMAJ), showed that the risk was more than double that in the first 6 months of metformin therapy.


In the 25-year, population-based study, Jean-Pascal Fournier, MD, PhD, and co-investigators compared metformin monotherapy with sulfonylurea monotherapy in a cohort of 74,300 patients with type 2 diabetes, aged 40 years and older, from 1988 to 2012.

Participants either had hypothyroidism that was being treated with at least 2 prescriptions for levothyroxine (5,689) or had normal thyroid function (59,937). Levothyroxine, a synthetic form of thyroxine (T4) that is converted to triiodothyronine (T3) by the body, was recently confirmed as the gold standard for the treatment of hypothyroidism in a review published by Jacqueline Jonklaas, MD, PhD, and colleagues in the journal Thyroid.


Researchers found 495 incidences of low TSH (<0.4 mIU/L) in the group with hypothyroidism, compared with 322 in the group with normal thyroid function. While metformin therapy did not appear to affect people with normal thyroid function, patients with underactive thyroids had a 55% increased risk of low TSH levels, compared with treatment with a sulfonylurea.

The risk was especially notable in the first 3 to 6 months of metformin therapy, with an increase of 130% compared with the risk seen in sulfonylurea therapy.