STEP-HFpEF: semaglutide in heart failure with preserved EF — March 2026

Dr.ObesityMed said:

Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.

That holds for the injectable. The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people quote them as if they were.

roxy_nash said:

All true, with one condition: that curve is for people who reached the dose on schedule.

Bookmarking. The distinction being drawn above is the one nobody else makes. Sending this to two other people who asked me the same thing last week.

Dr.ObesityMed said:

Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.

I will push back on the "any working dose is fine" framing. The maintenance evidence sits overwhelmingly at the top studied dose, and the extension data shows regain tracking dose reduction rather than tracking stopping. Holding low is reasonable; pretending it is evidentially equivalent is not.

GenomicsKate said:

My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.

Lp(a) and cardiovascular risk: a nuance that matters. Unlike most lipid markers, Lp(a) is 90%+ genetically determined and doesn't really change with weight loss or GLP-1 therapy.

My Lp(a) has remained at 67 nmol/L across all time points. If yours is elevated (>50 nmol/L), you need additional risk mitigation strategies regardless of your GLP-1 response. Don't assume your medication is covering all cardiovascular risk factors.

Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful.