Happy to weigh in on this. Creatine monohydrate is probably the single most studied supplement in sports nutrition history, with an extremely robust safety profile.
1. Safety with GLP-1 agonists: There is no known pharmacological interaction between creatine monohydrate and semaglutide/tirzepatide. They work through entirely different mechanisms. Creatine is stored in skeletal muscle; GLP-1 agonists work on incretin receptors. No contraindication.
2. Water retention: Yes, creatine causes intracellular water retention — typically 1-3kg in the first 1-2 weeks (the "loading" phase, though loading isn't necessary). This is INTRACELLULAR water pulled into muscle cells, which is actually beneficial for muscle protein synthesis. It is NOT subcutaneous water retention (bloating). However, if you're tracking weight loss on a scale, expect a temporary "stall" or slight increase when you start. This is not fat gain. Use waist measurements or DEXA alongside the scale.
3. Dosing: 5g/day of creatine monohydrate. Every day, not just training days. No loading phase necessary — you'll saturate stores in ~3-4 weeks at 5g/day vs ~1 week with a 20g/day load. The loading phase can cause GI distress, which is the LAST thing you need on GLP-1 meds.
4. GLP-1-specific considerations:
- Skip the loading phase (see above — GI risk)
- Take it with food if possible to improve absorption and reduce any stomach upset
- Creatine monohydrate, not HCL or other fancy forms — mono has the most evidence
- Stay well hydrated — you should be doing this anyway on GLP-1 but creatine increases the need
The kidney myth: Creatine does increase creatinine levels in blood tests, which can look like impaired kidney function to an uninformed clinician. If you're getting bloodwork, tell your doctor you take creatine so they don't misinterpret the results. Actual kidney damage from creatine in healthy individuals has never been demonstrated in clinical research.