My patient is being treated for a urinary tract infection with trimethoprim-sulfamethoxazole (TMP-SMX) and has developed hypoglycemia. Can it be related?

Yes! The sulfamethoxazole component of TMP-SMX contains the identical sulfanilamide structural group as sulfonylureas used as oral hypoglycemics1.  It appears to act through mimicking the action of sulfonyureas on the pancreatic islet cells by acting as an insulin secretagogue leading to increased insulin secretion1.   Increased levels of plasma insulin dropping  following interruption of TMP-SMX has been reported,  and is thought to be dose and time dependent1,2.

A major risk factor for this complication is impaired renal function, but poor hepatic function, and concurrent use of drugs that decrease plasma glucose levels have also been implicated (1,2).  Occasionally there are no obvious risk factors.

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 Bonus Pearl: Did you know that sulfonamides were first noted to cause hypoglycemia in 1942, when they were used for treatment of typhoid, paving the way for the development of sulfonylureas as the original oral hypoglycemic agents . The Power of observation strikes again!

References

  1. Forde DG, Aberdein J, Tunbidge A, et al. Hypoglycemia associated with co-trimoxazole use in a 56-year-old caucasian woman with renal impairment. BMJ Case Reports 2012;doi:101136/bcr-2012-007215.
  2. Nunnai G, Celesia BM, Bellissimo F, et al. Trimethoprim-sulfamethoxazole-associated severe hypoglycemia: a sulfonylurea-like effect. Eur Rev Med Pharmacol Sci 2010;14:1015-18.
My patient is being treated for a urinary tract infection with trimethoprim-sulfamethoxazole (TMP-SMX) and has developed hypoglycemia. Can it be related?

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