Taking the question as asked, rather than the general version of it. HbA1c reflects roughly three months of average glycaemia weighted toward the most recent weeks, which is why repeating it at six weeks tells you very little. The improvement on this class comes from two directions — direct glucose-dependent insulin secretion and glucagon suppression, plus the indirect effect of weight loss on insulin sensitivity — and the second continues after the first has plateaued.

Dr.NateNeph said:

HbA1c reflects roughly three months of average glycaemia weighted toward the most recent weeks, which is why repeating it at six weeks tells you very…

Agreeing with Dr.NateNeph, and the qualification matters more than the agreement. Orforglipron is a small molecule rather than a peptide, which is the whole point: no SNAC absorption enhancer, no fasting window, no cold chain, and oral bioavailability in the tens of percent instead of around one. Phase 2 put it near 14.7% weight loss at 36 weeks on the top dose with a side-effect profile that looks like the injectables.

That is the short version; the long version is somebody else's post.

RetaRick_CA said:

I have been following the oral non-peptide data since phase 2 and I am trying to work out how much of the enthusiasm here is about efficacy and how…

Agreed, with the caveat that HbA1c is unreliable in anaemia, haemoglobinopathies and recent blood loss, all of which are commoner than people assume. If it disagrees with fasting glucose or a CGM, that is worth chasing.

Adding the clinical framing, because it changes how the question reads. It helps to ask what evidence would change your mind before you look at any. If nothing would, the discussion is not about evidence, and it is better to say so early than to spend nine posts discovering it.