Diabetes patients taking SGLT2 inhibitors may exhibit false positive urine ethanol tests: NEJM

Despite not ingesting alcohol for over 10 months, the man in his early 60s tested positive in his urine for ethanol on the last four urine samples he provided to a probation office. None of the urine samples contained any traces of illicit or non-prescribed substances.

But after he called his primary care provider for fear of going to jail over the positive tests, the PCP's lab revealed no detectable ethanol in a new urine sample, Aaron L. Schwartz, MD, PhD, of the Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center in Philadelphia, detailed in the case study.

On the repeat urine test, they did not find ethanol, but the primary care lab did find the presence of glycosuria -- an expected finding as the patient was newly prescribed 20 mg daily of empagliflozin (Jardiance) just 5 months prior for his diabetes.

Schwartz called the city probation office to ask about their storage of urine samples. He was told that urine samples were samples were sent once daily to an external laboratory to be tested, but samples were not refrigerated before transport.

To test the theory, the primary care office took their new urine sample out of refrigeration. One day later the urine was retested for ethanol after it remained at room temperature for 24 hours. Now, the sample tested positive for ethanol.

He explained how the SGLT2 inhibitor drugs produce glycosuria even when blood glucose levels are within the normal range and also increase the presence of microbes in the urinary tract -- two ingredients needed for microbial fermentation.

Following the positive ethanol tests at the city probation centre, the urine sample collected by the primary care facility 3 days later had a glucose level of 1,000 mg/dL. It was negative for urinary ethyl glucuronide, urinary ethanol, nitrites, leukocyte esterase, blood, ketones, and bilirubin. A urine culture showed less than 50,000 CFU/mL of mixed gram-positive organisms.

According to Schwartz, since the class of SGLT2 inhibitors is frequently prescribed for a wide range of diabetes, kidney, and cardiovascular indications, this could have the potential to affect a lot of patients. The SGLT2 inhibitors include canagliflozin (Invokana), dapagliflozin (Farxiga), and ertugliflozin (Steglatro).

Given the potential for false positive results, he recommended that he would encourage clinicians to be mindful of whether a patient is subject to urine toxicology testing when taking this medication. A clinician should be somewhat sceptical of positive tests in these situations.

To conclude, SGLT2 inhibitors like empagliflozin are effective in diabetes management but can lead to unexpected test results. As science continues to evolve, so does understanding of these complex interactions. By staying vigilant and informed, patients and healthcare providers can navigate these challenges and ensure optimal diabetes management.

Reference:

Schwartz AL "SGLT2 inhibitors and false positive toxicology tests" N Engl J Med 2024; DOI: 10.1056/NEJMc2313463.