Tirzepatide

## What can go wrong **GI side effects** are common — about 45% of users report nausea during titration. Tirzepatide tends to produce slightly more GI symptoms than semaglutide at equivalent stages. **Severe lean mass loss** is the dominant performance risk. With weight losses averaging 21% of body weight, total lean mass loss can be 7-10 kg without intervention. Resistance training and high protein intake are mandatory, not optional, for performance-focused users. **Gallstones** are more common than with semaglutide, likely due to faster weight loss rates. Risk is around 1-3% per year. **Pancreatitis** is rare but reported. Persistent severe abdominal pain warrants immediate medical evaluation and drug discontinuation pending workup. **Gastroparesis** complicates anesthesia. Hold 1-2 weeks before elective surgery per ASA guidance. Several case reports describe aspiration during induction in users still on therapy. **Rebound weight gain** is well-documented. SURMOUNT-4 showed regain of much of the lost weight within a year of discontinuation. This is chronic therapy for most users. **Boxed warning** for medullary thyroid carcinoma based on rodent data — contraindicated in MEN2 or family history of MTC. Diabetic retinopathy can worsen transiently with rapid glycemic correction.