A 52-year-old woman lost 25 kg on semaglutide treatment, causing her implanted cardiac defibrillator to rotate within its subcutaneous pocket and twist its leads—a rare complication called Twiddler syndrome that required emergency intervention including treatment for cardiac tamponade. This case report identifies a previously unrecognized risk associated with GLP-1 receptor agonists like semaglutide and Ozempic. The dramatic weight loss these medications produce can loosen the tissue around implanted cardiac devices, allowing dangerous mechanical movement. This finding has immediate clinical relevance as millions now use GLP-1 drugs for weight management, and many also have pacemakers or defibrillators. Cardiologists and endocrinologists need awareness of this potential complication, particularly in patients losing substantial weight rapidly. While Twiddler syndrome affects less than 1% of device patients typically, the mechanism—loose subcutaneous tissue allowing device rotation—suggests the risk could be elevated in the GLP-1 era. The complication proved life-threatening in this case, requiring lead extraction surgery complicated by cardiac tamponade. This represents an emerging intersection between metabolic medicine and cardiac device management that warrants systematic monitoring and potentially modified surgical techniques for device placement in patients likely to experience significant weight loss.