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Alternative access routes: Private prescription: Available through private GPs, specialist weight management clinics, or online prescribing services, though costs are substantial Clinical trials: Some research studies recruit menopausal women, offering supervised access to these medications Diabetes indication: Women with type 2 diabetes may access GLP-1 receptor agonists through diabetes services according to NICE NG28 guidance [23] Patients should discuss their individual circumstances with their GP to determine eligibility and local access pathways

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Deamidation breaks the backbone Asparagine and glutamine residues in the tirzepatide sequence are vulnerable to deamidation, a chemical reaction where the amide group converts to a carboxylic acid

Of note is that tirzepatide was previously reported to cause biased signaling at GLP-1R in favor of cAMP response over -arrestin recruitment in the presence of 0.1% casein 39 , which was confirmed in the present study showing that non-acylated tirzepatide elicited better cAMP responses (EC 50 = 0.90 pM for 0.1% casein and 4.66 pM for 0.1% BSA) than that of tirzepatide (EC 50 = 3.05 pM for 0.1% casein and 103.10 pM for 0.1% BSA) (Supplementary Table 11) highlighting the impact of acylation on their pharmacological properties

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