A 40-year-old woman recently started a diabetic medication and reports recurrent flu-like symptoms. Which antidiabetic drug is associated with an increased risk of upper respiratory tract infections?

• A. Metformin
• B. Sitagliptin
• C. Pioglitazone
• D. Empagliflozin

Answer: (B)

Upper respiratory infections are a known adverse effect of DPP-4 inhibitors, the class that includes sitagliptin. These drugs raise incretin levels to improve glucose-dependent insulin secretion, but DPP-4/CD26 also plays a role in immune function. Modulating this pathway can modestly increase susceptibility to infections of the upper respiratory tract, especially early after starting therapy. That makes recurrent flu-like symptoms a plausible side effect for someone recently begun on this medication.

Other antidiabetic drugs have different common infection profiles: metformin is more often associated with GI upset; pioglitazone can cause fluid retention and weight gain with cardiovascular concerns; empagliflozin tends to raise risk of genital and urinary tract infections due to glycosuria. While infections can occur with any drug, the pattern and the specific association with upper respiratory infections point most strongly to sitagliptin.