Nick NorwitzMD PhD, Oxford-Harvard | Metabolic Health Educator | “Stay Curious”

This Drug Raises Cholesterol... and Saves Lives

10 Jan 2026 · 1 min

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1:24

In this monologue, the speaker highlights a paradoxical observation about SGLT2 inhibitor drugs: they markedly lower cardiovascular and all‑cause mortality (a 38% relative reduction in cardiovascular death reported in a 2015 New England Journal of Medicine trial) yet consistently raise LDL cholesterol levels, as documented in the trial’s supplementary appendix (Figure S3, Section P). The speaker points out that the LDL increase, while modest, is larger than in many studies where LDL is implicated in heart disease. He then challenges the prevailing narrative that LDL/ApoB are the primary drivers of cardiovascular risk, arguing that this oversimplification can be harmful. To explain the drugs’ benefit, he suggests mechanisms such as the clearance of senescent cells throughout the body, including in blood vessels, which may improve heart health independent of lipid levels. The talk concludes by urging listeners to look beyond a narrow LDL‑centric view of cardiovascular risk.

Chapters

There's a common medication that saves lives from cardiovascular disease, but get this— it increases cholesterol. Specifically, it increases LDL, bad cholesterol. Isn't that paradoxical? Well, in a landmark 2015 trial published in the New England Journal of Medicine, SGLT2 inhibitor medications reduced cardiovascular death by 38%— that was the relative risk reduction— and lowered all-cause mortality, all death. But if you dig into the supplementary appendix, Figure S3, in Section P at the end, you'll find a buried detail: LDL increase in the SGLT2 inhibitor treatment group. This is actually a known effect of these medications. The rise wasn't big, but it was actually larger than what's seen in other studies where LDL is blamed for increased heart disease risk. You can see the associated long-form content for more on that. And the mechanism? The way by which these SGLT2 inhibitors improve heart health? It's actually fascinating. So one example, they can help clear out senescent zombie-like cells throughout the body, including in blood vessels. My point isn't that L-ZL or ApoB don't matter. It's that the narrative we're often sold, that they're the primary drivers or ultimate measures of cardiovascular risk, is not just oversimplified, it's harmful. When we look at health through a keyhole, people suffer around us.