Semaglutide antibody formation — immunogenicity and efficacy loss

That's a fair point. I don't know what the titer was, just that it was "positive." I'll ask my endo for the specific numbers at my next visit. Could the test be wrong?

The standard screening assay (electrochemiluminescence bridging immunoassay) can have false positives, especially at low titers. A confirmatory step (usually competitive binding with excess drug) reduces false positives, and then a neutralization assay (cell-based, measuring inhibition of GLP-1R signaling) determines if the antibodies actually block the drug.

It's worth asking whether a neutralization assay was performed. Positive screening without confirmed neutralization is much less clinically meaningful.

u/SarahBee_macro also raises excellent points about metabolic adaptation. At a 47 lb weight loss, your TDEE has dropped significantly. Have you recalculated your caloric needs at your current weight? You may need to consciously reduce intake further or increase activity to continue losing — the medication is still working, but the goalposts have moved.

This is all incredibly helpful. I honestly hadn't considered that my TDEE dropped. I've been eating the same things as when I was losing weight but maybe that's now maintenance calories at my current weight? Ugh. Bodies are complicated.

I'm going to: (1) get the specific ADA titer and ask about neutralization assay, (2) recalculate my TDEE, and (3) discuss tirzepatide as a backup plan. Thank you all seriously 🙏