Known safety concerns, contraindications, and risk factors.
Semaglutide and tirzepatide are FDA-approved for type 2 diabetes and/or chronic weight management and must be used under prescribed medical supervision. Retatrutide is investigational (Phase 3 ongoing). Tesamorelin is approved for HIV-associated lipodystrophy — not for general insulin sensitisation. MOTS-c is an investigational compound (Phase 1a/1b). The Khavinson bioregulators (Pancragen and related) are not FDA-approved and their Western clinical evidence base is limited. AOD-9604, ipamorelin, CJC-1295, GHRP-2, GHRP-6, and MK-677 are research compounds without FDA approval for the indications discussed. 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 carcinoma or MEN 2
Liraglutide, semaglutide, and tirzepatide stimulated calcitonin release and caused thyroid C-cell tumours in rodent models. Human relevance is uncertain but the regulatory warning is explicit — use is absolutely contraindicated in these populations.
Active malignancy (tesamorelin)
Tesamorelin is contraindicated in patients with active cancer due to GH/IGF-1 axis effects on tumour biology. Patients with a history of recurrent malignancy are also generally excluded.
Pregnancy or breastfeeding
Tesamorelin administration in rats resulted in hydrocephaly in offspring. Tirzepatide and GLP-1s are contraindicated in pregnancy due to lack of human safety data and clear fetal risk. Human data on breastfeeding exposure is inadequate.
Prior episode of acute pancreatitis
Given the incretin pancreatitis case-report signal (including fatal haemorrhagic cases), prior pancreatitis markedly elevates recurrence risk. Patients with a pancreatitis history are generally excluded from these therapies.
Acute critical illness (tesamorelin)
GH and GHRH analogues are associated with increased mortality in patients who are critically ill following open-heart or abdominal surgery, multiple trauma, or acute respiratory failure. Tesamorelin should be discontinued in this setting.
Hypothalamic-pituitary axis disruption
Tesamorelin is contraindicated in patients with axis disruption from pituitary tumours, pituitary surgery, head irradiation, or significant head trauma.
Severe gastroparesis or active inflammatory bowel disease
GLP-1 and tirzepatide further delay gastric emptying, which is already impaired in gastroparesis. In active IBD, the GI side-effect profile can exacerbate symptoms significantly.
Pre-existing diabetic retinopathy
Rapid glycaemic improvement can trigger early worsening of established diabetic retinopathy, particularly with semaglutide.
Dependence on oral hormonal contraception (tirzepatide)
Tirzepatide decreases efficacy of oral hormonal contraceptives via delayed gastric emptying. Contraceptive failure is a documented concern.
Concurrent warfarin therapy
Delayed gastric emptying from GLP-1s may alter warfarin absorption and INR stability.