Pain Relief Drug Tramadol Associated with Hypoglycemia Interview with:
Ruben Abagyan, Ph.D.

Dr. Abagyan

Professor, University of California, San Diego
Skaggs School of Pharmacy & Pharmaceutical Sciences
San Diego Supercomputer Center  What is the background for this study?  What are the main findings?

Response: The background for this study was concern about unknown side effects of tramadol that became a popular treatment for chronic pain. With our informatics approach and access to millions of the FDA reports we were in a position to look for those adverse effects and we found that hyperglycemia (low blood sugar) is one of those concerns. There have been a few small-scale studies and case reports of tramadol use associated with hypoglycemia and hospitalizations related to it. The dramatic increase in tramadol prescription rates, especially in light of tighter control over hydocodone/acetaminophen (went from schedule III to II), warranted a larger scale postmarketing study of FDA FAERS reports.

As we compared the hypoglycemia side effect between different opioids we found that only one other drug, methadone (used to treat drug abuse and addiction), has a comparable association with hypoglycemia. What should readers take away from your report?

Response: Patients using tramadol should should be aware of hypoglycemia symptoms such as shakiness, dizziness, sweating, hunger, irritability, moodiness, anxiety/nervousness, and headache, or, in severe cases, blurred vision, seizures or loss of consiousness.  The same applies to methadone, also known as Dolophine. What recommendations do you have for future research as a result of this work?

Response: It may be beneficial to perform controlled studies to confirm and understand this association. Our study looked at other drugs with the known pharmacology of tramadol (mu-opioid agonism, serotonin/norepinephrine re-uptake inhibition, and NMDAR antagonism), but did not find an association with hypoglycemia with a specific class.  Would be interesting to learn more about additional/other pharmacology of tramadol and methadone behind the etiology of hypoglycemia. Is there anything else you would like to add?

Response: We think that studies of this nature are beneficial since rare side effects often go unnoticed in clinical trials due to a limited number of participants. Additionally, hypoglycemia effects may often be attributed to other medications and medical conditions, while tramadol or methadone were unlikely to cause suspicion.

Any disclosures?

Non of the authors have any financial or non-financial conflicts of interest to disclose. 


Tigran Makunts, Andrew U, Rabia S. Atayee, Ruben Abagyan. Retrospective analysis reveals significant association of hypoglycemia with tramadol and methadone in contrast to other opioids. Scientific Reports, 2019; 9 (1) DOI: 10.1038/s41598-019-48955-y

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