Comparative risk of severe hypoglycemia among concomitant users of thiazolidinedione antidiabetic agents and antihyperlipidemics

•Concomitant thiazolidinedione + fibrate use was associated with a ∼1.5- to 2.5-fold increased risk of severe hypoglycemia.•This increased risk generally manifested after the first month of concomitant use.•Severe hypoglycemia occurs in some patients receiving a thiazolidinedione, even without concomitant exposure to insulin or a sulfonylurea.•The apparent drug interaction between thiazolidinediones and fibrates is an underappreciated cause of severe hypoglycemia.•Clinicians should be attuned to both immediate- and delayed-onset hypoglycemia in their patients treated concomitantly with thiazolidinediones and fibrates.

We conducted high-dimensional propensity score-adjusted cohort studies to examine whether thiazolidinedione use with a statin or fibrate was associated with an increased risk of severe hypoglycemia. We found that concomitant therapy with a thiazolidinedione + fibrate was associated with a generally delayed increased risk of severe hypoglycemia.