A 66‑year‑old woman on a mechanical heart valve started tirzepatide for obesity and, after 10 days, her blood thinner (warfarin) levels (INR) dropped unexpectedly. The drop wasn’t due to diet changes and was likely because tirzepatide slows stomach emptying, affecting how warfarin is absorbed. Doctors had to raise her warfarin dose and keep a closer eye on INR for several weeks.

Tirzepatide is a medication capable of controlling blood glucose levels through the dual agonism of GIP and GLP-1 receptors. In particular, GLP-1 reduces food intake and delays gastric emptying. We report the case of a 66-year-old woman hospitalised with a medical history notable for grade III obesity and a mechanical mitral valve prosthesis. Given the severity of obesity and the high overall cardiovascular risk, tirzepatide was initiated on the day after admission. After 10 days of therapy, routine blood tests revealed an unexpectedly significant reduction in INR values, despite the patient following a strict and stable diet. The therapeutic INR target was gradually achieved only after approximately three weeks of progressive increases in daily warfarin dosage. Although tirzepatide has no known direct effects on INR, it could indirectly influence its values by delaying gastric emptying. In patients treated concomitantly with tirzepatide and warfarin, closer INR monitoring may therefore be advisable, even in the absence of dietary or pharmacological changes. Tirzepatide may indirectly affect the pharmacokinetics of warfarin.In patients receiving both warfarin and tirzepatide, closer INR monitoring may be required.Careful attention to potential drug interactions is warranted, even when no direct interaction is known.