The popular pain reliever tramadol is associated with hypoglycemia, according to a new study from the United Kingdom. In a nested case-control analysis conducted in the United Kingdom, tramadol was compared to codeine for non-cancer pain between 1998 and 2012. Cases of hypoglycemia were matched with up to 10 controls on age, sex, and duration of follow-up in a study that included more than 330,000 patients. Compared to codeine, tramadol use was associated with an increased risk of hospitalization for hypoglycemia (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.09-2.10), particularly in the first 30 days of use (OR, 2.61; 95% CI, 1.61-4.23). This was confirmed in both cohort and case-crossover analyses. The authors conclude that initiation of tramadol therapy is associated with an increased risk of hypoglycemia requiring hospitalization (JAMA Int Med, published online Dec 8, 2014, doi:10.1001/jamainternmed.2014.6512). This study is important because the use of tramadol has increased in the past few years. The drug is a weak opioid analgesic that was only recently placed in schedule IV. Tramadol has been viewed by some physicians as an alternative to hydrocodone, which was moved from schedule III to the more restrictive schedule II in August. Tramadol has been reported to cause hypoglycemia in those with no known risk factors in up to 40% of cases.