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Tramadol Associated with Increased Rate of Hypoglycemia

Clinical question: Does tramadol increase rates of hospitalization from hypoglycemia compared to other opioids?

Background: As tramadol use has increased in the general population, there have been multiple reports of hypoglycemia after initiation of the painkiller, including in patients with no other known risk factors, such as diabetes mellitus.

Study design: Case control study.

Setting: United Kingdom.

Synopsis: Using the United Kingdom’s Clinical Practice Research Datalink, a cohort of 334,034 patients was identified, including 1,105 hospitalized for hypoglycemia. To compare incidence of hypoglycemia in patients taking tramadol versus nontramadol opioids, patients newly treated with tramadol for noncancer pain were compared with those treated with codeine.

Use of tramadol was associated with increase in hospitalization for treatment of hypoglycemia compared with codeine. Specifically, tramadol use had an odds ratio (OR) of 1.52 (95% confidence interval, 1.09-2.10). The risk of hypoglycemia was higher in the first 30 days of use, with an OR of 2.61 (95% confidence interval, 1.61-4.23).

Since tramadol prescribing has increased over the past 10 years, clinicians should be mindful of the potential association between tramadol and severe hypoglycemia requiring hospitalization. Although the details of the pathophysiology leading to this outcome remain unclear, evidence of a causal relationship is mounting. The association with hypoglycemia was seen particularly in the first 30 days of therapy. The incidence of less severe hypoglycemia not requiring hospitalization remains unknown.

Bottom line: Tramadol use is associated with increased rates of hypoglycemia requiring hospitalization.

Citation: Fournier JP, Azoulay L, Yin H, Montastruc JL, Suissa S. Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain. JAMA Intern Med. 2015;175(2):186-193.

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