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Evidence-based GLP-1 & peptide discussion since 2023
ForumsTirzepatide (Mounjaro / Zepbound)Tirzepatide and cholesterol — LDL/HDL ratio improvements

Tirzepatide and cholesterol — LDL/HDL ratio improvements

Dr.LipidDallas Sat, May 23, 2026 at 8:05 AM 12 replies 374 viewsPage 1 of 3
Dr.LipidDallas
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May 23, 2026 at 8:05 AM#1

Read the primary source rather than the write-up and the two do not agree, so here is what is actually in it.

ApoB is the more informative number and it is cheap. LDL-C estimates cholesterol mass in atherogenic particles; ApoB counts the particles, and it is particle count that tracks risk — which is why the two can disagree and why the disagreement is the clinically interesting case. Triglycerides fall substantially with weight loss and improved insulin sensitivity, HDL moves modestly, and LDL-C often barely moves at all, which surprises people who expected everything to improve together.

Where I think it is weakest: the follow-up is short relative to how long people actually take these drugs, so durability is an assumption here rather than a finding.

So the question, as narrowly as I can put it: whether an unchanged LDL-C alongside a large triglyceride fall is a good result or a bad one, because ApoB and LDL-C seem to be telling different stories. Numbers rather than impressions, if you have them.

Note on sourcing:
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
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julia.endo
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May 23, 2026 at 8:11 AM#2
Dr.LipidDallas said:
ApoB is the more informative number and it is cheap.

True, though the ladder is longer and that is not a neutral detail — six dose steps means six opportunities to stall on the way up, and plenty of people never reach the dose the headline number came from.

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JessicaH_TX
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May 23, 2026 at 8:17 AM#3
Dr.LipidDallas said:
ApoB is the more informative number and it is cheap.

Careful with treating an unchanged LDL-C as a failure. If ApoB and triglycerides both fell, the particle picture improved regardless of what the calculated LDL says.

Ask again with the specifics and you will get a better answer than this one.

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sarah_TO
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May 23, 2026 at 8:23 AM#4

Answering the narrow version, because the broad one does not have a single answer. The GIP arm is doing real work rather than padding the label. GIP receptor agonism appears to improve adipose insulin sensitivity and lipid handling, and — counter-intuitively — GIP signalling in the CNS reduces nausea rather than adding to it, which is why tolerability at high total agonism is better than the GLP-1-only comparison would predict. SURPASS-2 is the cleanest head-to-head: tirzepatide beat semaglutide 1mg at every dose tier.

Happy to go further on any of that.

Last edited: May 23, 2026 at 12:23 PM
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chris_chi24
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May 23, 2026 at 8:51 AM#5
julia.endo said:
True, though the ladder is longer and that is not a neutral detail — six dose steps means six opportunities to stall on the way up, and plenty of…

Same experience, arrived at from the opposite direction.

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