Every single statin denialist I’ve interacted with has also been an LDL cholesterol denialist, without fail. Really remarkable.
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I might change my statin (currently atorvastatin) to a less glucose/insulin impacting version. My fasting blood glucose levels have been hovering around the 95 to 105 level and I’m wondering if changing statin might lower these…
ChatGPT Query: are some statins better than others in terms of contributing to insulin resistance, increasing the risk of type 2 diabetes, and significantly lowering GLP-1 levels in human?
Yes — different statins vary in how much they affect insulin resistance, type 2 diabetes (T2D) risk, and GLP-1 levels. Here’s a breakdown based on the best available clinical and mechanistic data:
1. Insulin Resistance & Diabetes Risk
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Higher risk (more likely to impair insulin sensitivity and increase T2D incidence):
- Atorvastatin (especially 40–80 mg)
- Rosuvastatin (20–40 mg)
-
Simvastatin (at higher doses, e.g., 80 mg)
→ These are “high-intensity” statins and show the clearest signal for increased diabetes risk in trials and meta-analyses.
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Lower risk (neutral or sometimes beneficial for insulin sensitivity):
- Pravastatin – may even improve insulin sensitivity (WOSCOPS trial).
- Pitavastatin – considered metabolically neutral or slightly favorable; marketed in Asia with this distinction.
- Fluvastatin – limited data, but generally seen as lower-risk.
2. GLP-1 Levels
-
Evidence (still limited, mostly small human studies + animal work):
- Simvastatin & Atorvastatin – associated with blunting GLP-1–mediated insulin secretion after meals, possibly by altering gut L-cell function.
- Rosuvastatin – some studies suggest mild GLP-1 reduction, but evidence weaker than atorvastatin/simvastatin.
- Pravastatin & Pitavastatin – appear to have little to no effect on GLP-1; some data suggest neutrality.
- Fluvastatin – minimal data, but not strongly linked to GLP-1 suppression.
3. Mechanistic Takeaways
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Statins impair glucose metabolism through:
- Reduced insulin sensitivity in muscle and liver.
- Impaired pancreatic β-cell insulin secretion.
- Decreased adiponectin (insulin-sensitizing hormone).
- Possible direct suppression of GLP-1 secretion in the gut.
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Potency, dose, and lipophilicity matter:
- Lipophilic statins (simvastatin, atorvastatin) penetrate tissues more widely → higher chance of affecting insulin/GLP-1 pathways.
- Hydrophilic statins (pravastatin, rosuvastatin) have more liver-targeted action → rosuvastatin still increases diabetes risk at high dose, but pravastatin seems protective.
Bottom Line
- Most diabetogenic / GLP-1 lowering: atorvastatin, simvastatin, rosuvastatin (high dose).
- Least diabetogenic / GLP-1 neutral: pravastatin, pitavastatin (possibly fluvastatin).
- Middle ground: lovastatin, moderate-dose rosuvastatin.
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If it’s diabetes risk you care about, atorvastatin is better than rosuvastatin. Just like with other side effects, testing around.
Use CGM’s as well before and after swapping. Do a OGTT before and after. Peter Attia knows a lot about this.
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My LDL-C is extremely low right now - around 46 I think at last measure, so I’m thinking of moving to pravastatin to see how it impacts my fasting glucose levels. I don’t worry if my LDL-C / APO-B goes up a few points.
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That’s what Brad Stanfield did. Not something I think is future proof. I’m suspecting we will learn that lower is better for sure. It’s not going in the other direction.
Fasting glucose is not that informative on its own, that I know. But if you can keep your glucose lower while apoB the same that’s better of course.
It’s an interesting question… which is more damaging to the body, 5 or 10 points on LDL-C or fasting Blood glucose measurements? I don’t think we have an answer yet do we?
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I’ve not really heard people talk about fasting glucose in isolation, it’s always relative to insulin levels taken at the same time for HOMA-IR calculation, and even better is OGTT according to Peter Attia. Of course there are association studies of the optimal levels but it might be a separate issue.
As he wrote, it’s the non-HDL-C and apoB that matters, not lowering to a specific triglyceride level (which is e.g a marker of insulin resistance/diabetes).
AI answer:
An isolated +10 mg/dL rise in apolipoprotein B (apoB) with a simultaneous –10 mg/dL drop in fasting glucose is generally more harmful than the opposite change (‑10 mg/dL apoB, +10 mg/dL glucose), especially when the glucose change stays within the normal range.
Why a 10‑mg/dL increase in apoB carries more risk
Factor What the number means Typical risk per 10‑mg/dL change (approx.) Why it matters apoB Each 10 mg/dL rise reflects ≈10 % more circulating atherogenic particles (VLDL‑apoB, LDL‑apoB, Lp(a)‑apoB). ≈6–9 % higher risk of major atherosclerotic cardiovascular disease (ASCVD) events in prospective cohorts, independent of LDL‑C. apoB is the direct count of atherogenic lipoprotein particles; every extra particle can enter the arterial wall, become oxidized, and trigger plaque formation. Fasting glucose A 10‑mg/dL rise is ≈0.55 mmol/L. In a person whose glucose is already in the normal range (e.g., 85 → 95 mg/dL) this is still well below the diabetic threshold (126 mg/dL). ≈1–2 % higher risk of ASCVD (if glucose stays <100 mg/dL) and very modest impact on microvascular risk. Glucose‑related damage is largely a function of chronic hyperglycemia (≥126 mg/dL fasting) or sustained elevations that raise HbA1c >6.5 %. A single 10‑mg/dL bump rarely pushes a normoglycemic person into that high‑risk zone.
It makes sense, as long as you’re not diabetic or becoming so and harming the arteries with excess glucose, it’s better.
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The FDA approved Repatha for primary prevention. https://www.medpagetoday.com/cardiology/dyslipidemia/117148
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Unfortunately there are always tradeoffs.
“Compared with baseline values, patients treated with atorvastatin had no change in atheroma burden, whereas patients treated with pravastatin showed progression of coronary atherosclerosis.”
Of course this paper’s subjects had a higher BMI, and the dosages were not adjusted so it’s not exactly apples to apples.
As I previously posted, I will give TUDCA a trial.
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That is a really interesting question!
This suggests there are threshold effects for hba1c
" There was a non-linear relationship between mean HbA1c during follow-up and the risks of macrovascular events, microvascular events and death. Within the range of HbA1c studied (5.5–10.5%), there was evidence of ‘thresholds’, such that below HbA1c levels of 7.0% for macrovascular events and death, and 6.5% for microvascular events, there was no significant change in risks (all p > 0.8). Above these thresholds, the risks increased significantly: every 1% higher HbA1c level was associated with a 38% higher risk of a macrovascular event, a 40% higher risk of a microvascular event and a 38% higher risk of death (all p < 0.0001)."
Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds | Diabetologia)
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I guess so. End of the day, we are not chimps or lions and I just don’t think we should be setting them up as any sort of comparison. Lion diets consist entirely of red meat and they don’t get heart attacks. Weirdly the horse has high cholesterol, but they are cardiovascularly extremely fit. I think every organism has unique physiology.
Yep, and honestly, I think these lipidologist people are also making a mistake of getting into the weeds on this sort of argument. The whole “appeal to nature” thing is bullshit. I also think that “20-40mg/dl is normal” is a stupid statement. It’s trying to hijack the natural = best argument. It would simply be better to say 20-40mg/dl is optimal for ASCVD prevention, without trying to make appeals to nature IMO.
The key word here is “potential”. As far as I know, the actual evidence still massively favours using statins. To get excited about changes in GLP-1 or bacterial metabolites is maybe putting the cart in front of the horse. It’s academically interesting but I don’t think it’s worth the “hype”. As @desertshores says, there are always trade-offs. The important thing is overall outcomes. You take a statin to address one thing, which causes something else to change, and then something else (like TUDCA) is taken to address that. But TUDCA itself has drug interactions, so the cycle will never end haha.
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First time I’ve heard this advice. Is it true? If so, it seems quite handy when having a heart attack.
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AMA kinda says no: Cough CPR: Not endorsed by the AHA | American Heart Association quote:
“Cough CPR” may be a temporary measure in settings such as the cardiac catheterization laboratory where patients are conscious and constantly monitored (for example, with an electrocardiogram machine). A nurse or physician can instruct and coach patients to cough forcefully every one to three seconds during the initial seconds of a sudden arrhythmia. But because it’s not effective in all patients, it shouldn’t delay definitive treatment.
So if you knew it was an arrhythmia, maybe go for it, but otherwise, would it hurt? How would you tell if it was arrhythmia? Idk. Just be sure to call 911 first—that’s my dithering dilettantic dabble on the matter.
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From 2016.
Comparative Effectiveness of Personalized Lifestyle Management Strategies for Cardiovascular Disease Risk Reduction
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Wow, Yoga for the win! We need more studies like this with ranked magnitude of risk reduction.
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Not sure if this has been posted:
Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques
https://www.ahajournals.org/doi/10.1161/JAHA.125.041521
Latent chronic bacterial inflammation evades immune detection and may contribute to the pathogenesis of complicated atherosclerotic plaques and fatal myocardial infarction.
Finnish press release about it:
https://www.tuni.fi/en/news/myocardial-infarction-may-be-infectious-disease
A pioneering study by researchers from Finland and the UK has demonstrated for the first time that myocardial infarction may be an infectious disease. This discovery challenges the conventional understanding of the pathogenesis of myocardial infarction and opens new avenues for treatment, diagnostics, and even vaccine development.
According to the recently published research, an infection may trigger myocardial infarction. Using a range of advanced methodologies, the research found that, in coronary artery disease, atherosclerotic plaques containing cholesterol may harbour a gelatinous, asymptomatic biofilm formed by bacteria over years or even decades. Dormant bacteria within the biofilm remain shielded from both the patient’s immune system and antibiotics because they cannot penetrate the biofilm matrix.
A viral infection or another external trigger may activate the biofilm, leading to the proliferation of bacteria and an inflammatory response. The inflammation can cause a rupture in the fibrous cap of the plaque, resulting in thrombus formation and ultimately myocardial infarction.
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This might explain why Nattokinase (high dose), Serrapeptase and Lumbrokinase seem to be able to reverse atherosclerotic plaques : These are all enzymes that can dissolve biofilms.
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