Tramadol Therapy Associated with Heightened Risk for Hypoglycemia

Initiation of tramadol therapy is associated with increased risk of hospitalization for hypoglycemia compared with codeine treatment, according to a case-control study in JAMA Internal Medicine.

Using U.K. prescription and hospital databases, researchers identified over 330,000 adults who began treatment with oral tramadol or codeine for noncancer pain between 1998 and 2012. They then matched roughly 1100 patients who were hospitalized for hypoglycemia over 5 years’ follow-up with 1100 who were not.

Compared with codeine use, tramadol was associated with a 52% increased risk of hospitalization for hypoglycemia, a risk that was highest within the first 30 days of treatment. The incidence of hypoglycemia hospitalization in the first 30 days was 3.0 per 10,000 person-months with tramadol versus 0.7 per 10,000 with codeine.

The researchers propose that tramadol may induce hypoglycemia through its effects on opioid receptors and its inhibitory activity on serotonin and norepinephrine reuptake.