Introduction: Pioglitazone is a medication that can be utilized in the management of type 2 diabetes mellitus (T2DM). It can be associated with adverse effects such as edema, weight gain, and heart failure. It is not commonly associated with pleural effusions. Case Presentation: Our case involves an 81-year-old man with T2DM who presented to the emergency department due to progressively worsening lower extremity edema and exertional dyspnea. These symptoms began after the patient started to regularly take pioglitazone. He had a large pleural effusion and diffuse anasarca. Pioglitazone was discontinued and he underwent successful thoracentesis and diuresis. Discussion: The Naranjo scale yielded a score of 7 points, indicating a probable association between pioglitazone and our patient’s presentation. There is limited documentation of pleural effusions associated with pioglitazone. Our case is unique as the patient had pleural effusions and anasarca associated with pioglitazone.
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