Known safety concerns, contraindications, and risk factors.
Semaglutide and tirzepatide are FDA-approved for chronic weight management and type 2 diabetes and must be used under prescribed medical supervision. Retatrutide, cagrilintide, and BRP are investigational molecules without approved therapeutic status at time of writing. AOD-9604 is a research compound — failed its primary weight-loss endpoint in 2007 — and is prohibited by WADA. This protocol is not medical advice, not a prescription, and not a recommendation to self-administer any substance. If you choose to use any of these compounds, do so with qualified medical supervision, pharmaceutical-grade sourcing, and full awareness of the legal status in your country. Pharmaceutical-grade sourcing is not a preference; it is the highest-impact safety decision in this protocol.
Personal or family history of medullary thyroid cancer or MEN 2A/2B
Rodent studies show GLP-1 / dual / triple agonists stimulate thyroid C-cell hyperplasia and tumour growth. Human evidence is unconfirmed but the regulatory warning is explicit and strict.
Prior episode of acute pancreatitis
Given the GLP-1 pancreatitis case-report signal (including fatal haemorrhagic cases), prior pancreatitis elevates risk of recurrence. Patients with a pancreatitis history are generally excluded from these therapies.
Pregnancy or breastfeeding
Animal studies show skeletal and visceral malformations. Human data is inadequate to evaluate risk to mother or infant. Broadly contraindicated across the entire class.
Severe renal or hepatic dysfunction
AKI risk from volume contraction elevates in renal dysfunction. Hepatic clearance matters for specific molecules. Available data on safety and dose adjustment in severe impairment is sparse.
Severe gastroparesis or active inflammatory bowel disease
GLP-1 and dual-agonist therapy further delays gastric emptying, which is already impaired in gastroparesis. In active IBD, the GI side-effect profile can exacerbate symptoms.
Unstable or severe cardiovascular disease
Dose-dependent sinus tachycardia on dual and triple agonists can destabilise arrhythmic or ischaemic substrate. Perioperative aspiration risk is also load-bearing in this population.
Competitive athletes under WADA jurisdiction (AOD-9604 specifically)
AOD-9604 is on the WADA Prohibited List. GLP-1 agonists are not currently prohibited for general use but policy is evolving — check current WADA status before competition.