Known safety concerns, contraindications, and risk factors.
Semaglutide and tirzepatide are FDA-approved for type 2 diabetes and chronic weight management and must be used under prescribed medical supervision. MOTS-c and related mitochondrial-derived peptides are research compounds without approved therapeutic status in the US, UK, or EU. Pankragen and the Khavinson bioregulators have clinical use in Russia but are not approved as therapeutics in Western jurisdictions. 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.
Personal or family history of medullary thyroid cancer or MEN 2A/2B
Rodent studies show GLP-1 agonists stimulate thyroid C-cell hyperplasia and tumour growth. Human evidence is unconfirmed but the regulatory warning is explicit and strict.
Pregnancy or breastfeeding
Safety has not been established for any peptide in this protocol during pregnancy or lactation. GLP-1 agonists, growth-hormone analogues, and bioregulators are all broadly contraindicated.
Severe gastroparesis or active inflammatory bowel disease
GLP-1 analogs further delay gastric emptying, which is already impaired in gastroparesis. In active IBD, the GI side-effect profile may exacerbate symptoms.
Severe renal dysfunction (eGFR <30)
Weekly exenatide is specifically avoided in moderate renal failure. All GLP-1 agonists are avoided in severe renal dysfunction due to reduced clearance and increased AKI risk from volume contraction.
Prior episode of acute pancreatitis
Given the GLP-1 pancreatitis case-report signal (including fatal haemorrhagic cases), prior pancreatitis elevates the risk of a recurrence on GLP-1 therapy.
Active malignancy (MOTS-c and Pankragen)
Peptide bioregulators and MDPs with cell-growth or pro-regeneration signalling carry theoretical concern in active malignancy. Evidence is thin but the principle of precaution applies.