Distinctive odor of metformin may lead to patient discontinuation

A distinctive fishy odor associated with metformin may cause patients to discontinue use of the drug, and researchers urge physicians to inquire more closely about aversion to the odor of the medication, according to a recent letter published in the Annals of Internal Medicine.

Although previous research has documented that metformin causes adverse gastrointestinal effects, the odor of metformin has not been reported in medical literature. However, Internet postings have addressed the peculiar odor of the drug. Pharmacists are aware of the odor, as well. An informal survey of several pharmacists found that they could readily identify metformin by the odor, which was described as fishy or “like old locker room sweat socks.”

The odor associated with metformin varies between generic versions and seems to be less noticeable with extended release formulations. Bristol-Myers Squibb, manufacturer of Glucophage, has also received complaints about odor.

The letter also included two case reports of patient discontinuation because of odor.

Case one was an adult man with diabetes who had taken Glucophage for years with no reports of adverse events. However, when switched to the generic, immediate-release drug, he reported a “dead fish” smell and discontinued use. After he was then given a generic, ER formulation, he reported no further problems at follow-up.

Case two was another adult man with diabetes who discontinued use of generic metformin also because of a fishy odor that nauseated him. This patient did not want to try an ER formulation.

The researchers questioned why this reaction to metformin has not been previously reported. They postulated that “patients may report that metformin nauseates them but do not further elaborate or distinguish this as a visceral reaction to the smell of the medication” and “physicians probably interpret the report of nausea in light of well-known gastrointestinal side effects of the medication and do not pursue the issue further.”

The researchers concluded that further research on this nonpharmacologic adverse event of metformin is needed. Perhaps a trial of a film-coated, ER formulation may be a reasonable approach. - by Jennifer Southall

This is usually a non-issue, although the occasional patient declines metformin for this reason. Those patients can then take the more expensive brandname products, although our peculiar reimbursement system is such that this may require inordinate effort!

- Zachary T. Bloomgarden, MD
Endocrine Today Editorial Board member

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