I switched around February, so it’s been a solid 6 months. Atorvastatin is known to cause muscle soreness for me, which is why I switched from EOD Atorvastatin to Pitavastatin.
Also my mother switched from 10 mg Atorvastatin every day to Pitavastatin 2 mg every day and muscle soreness went away for her as well. Unfortunately I don’t have new blood work for her yet to see the effects although her ApoB is 34 using Atorvastatin and Ezetemibe only. Her triglycerides are the big problem.
Even pitavastatin turned out to be incompatible with me so I’m currently waiting for Ubeslo.
Use RW-ApoB in the case for high trigs and/or Lp(a) for an adjusted apoB level: RW-ApoB -- Superior Metric For Lipid Related CVD Risk --- Using Lp(a), ApoB, and Triglycerides
Although I’m unsure if it’s wise to go lower than 30 mg/dl apoB so fixing the cause of the high triglycerides become more important.
Just got labs again staying on 4mg Pitavastatin, 10mg Ezetimibe, and 2mg weekly Retatrutide. LDL further dropped from 44 to 36. HDL went from 50 to 55. Didn’t check ApoB this particular time but I would imagine it has continued to drop as well (it was 44 last time). I haven’t seen an HDL that high since pre-testosterone use. Still no muscle pains (I had some on Rosuvastatin).
Also for those worrying about A1C. Mine dropped to 5.0 (I am still on 10mg empagliflozin and 100mg Acarbose daily along with the retatrutide so no changes there).
So we’re seeing lowered LDL and ApoB and higher HDL with lower HBA1C. That’s all excellent!
Yes I love this particular statin. When I was only using 2mg, my LDL was 55 (same pharmacology for everything else so I know the additional drop was from a dose increase). Not to mention it showed lowered biological aging on that aging clock study Sinclair posted a few months ago that was discussed (for what that’s worth).
https://onlinelibrary.wiley.com/doi/10.1002/jcp.27932
Interesting that CoQ10 supplementation, which appears generally to not be helpful for myalgia in most statin users, may actually be helpful in protecting the pancreas against statin toxicity.
Discussion of mechanisms of pancreatic toxicity from statins:
So possibly attenuate the increase risk in diabetes (what about other LLT – as genetic evidence suggest ALL LDL-c lowering drugs increase diabetes risk)?
(P.S to the readers don’t stop LLT based on this, the reward:risk is way more in favor than any risk increase from diabetes).
That would depend on the proposed mechanism. Despite the theoretical risk posed by Mendelian randomization, apparently there’s zero increased risk of diabetes in PCSK9i studies.
Hmm, that’s right, so if there isn’t any increase in diabetes in any of the other drugs RCT’s, despite the MR data, then that means they don’t increase diabetes risk, at least relative to statins (pitavastatin also increases diabetes risk, despite any relative improvements in glucose compared to other statins).
RCT > MR, anyway.
The situation with pitavastatin and CoQ10 is more nuanced. There are some conflicting results based on either direct serum measurement or proxy effects. Here’s an example:
Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia: results from a crossover study
https://pubmed.ncbi.nlm.nih.gov/17957184/
“Under these conditions, plasma levels of CoQ10 were reduced by atorvastatin (-26.1%, P=0.0007) but not by pitavastatin (-7.7%, P=0.39), although no adverse events or abnormalities of liver and muscle enzyme were observed after either statin treatment.”
Effect of Statins (Atorvastatin, Pitavastatin, Pravastatin, Rosuvastatin and Simvastatin) and Coenzyme Q10 (CoQ10) on Adenosine Triphosphate (ATP) Levels
https://www.lipidjournal.com/article/S1933-2874(15)00112-9/fulltext
“Antimycin-A, the positive control, significantly reduced the ATP levels. The ATP levels in simvastatin and atorvastatin treated cells were not significantly different from antimycin-A. While ATP levels in rosuvastatin, pitavastatin and pravastatin (p<0.05) treated cells were significantly different from antimycin-A. Addition of CoQ10 ameliorated the negative effects of atorvastatin (p<0.001); rosuvastatin (p=0.009) and simvastatin (p=0.026) on ATP levels in the adipocytes while presence of CoQ10 in pitavastatin treated cells caused further significant reduction in ATP levels (p=0.001).”
So supplementing with CoQ10 might have some effect with simvastatin, atorvastatin and rosuvastatin, but differential effects with pitavastatin. Of course this is a cell-based mechanistic finding with antimycin-A as a readout, but interesting nonetheless. If pitavastatin does not significantly affect serum CoQ10, then it matters less for downstream effects. What we need are more rigorous long term outcome studies with CoQ10 and these statins, because the studies so far supplementing with CoQ10 in the presence of statins are not encouraging. But in general I’m not sure CoQ10 is a fruitful direction here - I don’t think it makes much if any difference. YMMV.
The idea with CoQ10 supplementation for statin toxicity in pancreas would be purely as a mitochondrial antioxidant protecting against statin-induced oxidative damage rather than to correct a CoQ10 deficiency. One of the studies mentioned in the OpenEvidence discussion apparently showed that N-acetylcysteine also protected against the statin toxicity, so there are multiple candidates that might work including ergothioneine.
Honestly I have a higher hope for ergothioneine than CoQ10, because in studies tracking molecules associated with good health/longevity outcomes ergo was the one that stood out. Meanwhile other than heart failure there’s not much to hang you hat on with CoQ10. Of course, either way it’s a pretty thin reed to place much weight on. I think we need better studies.
How do you measure efficacy? IIRC it’s not possible to reverse diabetes (except its effects like elevated glucose) due to the entropic damage from exposures in e.g the pancreas.
Could you like scan the pancreas or use some biomarker (except diabetes biomarker – that’s I think a later stage finding, correct me if I’m wrong)?
Now you are moving further afield wrt, statins. Just looking at protecting pancreatic beta cells, there’s imeglimin:
Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules
Honestly, I’m more interested in imeglimin for countering possible negative effects of rapamycin than strictly diabetic glucose control. Rapamycin might be toxic to pancreatic beta cells, which was clearly shown in mice and hinted at in human transplant patients. Big “do not want” here for me wrt. rapamycin. YMMV.
Pancreas biopsy😂. This would be best tested first in mice/rats to demonstrate protection by a mitochondrial antioxidant from statin-induced pancreatic toxicity.
GLYNAC seems like it would have great potential here.
I actually do take 200mg Ubiquinol daily as well in case that’s another factor in my A1C dropping on Pitavastatin
I have been taking Pita since January and do not notice any of the muscle tightness or soreness I experienced with other statins, and my HBA1C has remained flat or dropped. This is by far my preferred statin.
Caution advised. Good quality evidence for this is entirely lacking. Cole has posted a bunch of papers which don’t amount to much at all. The supposed cytotoxic effects of statins on pancreatic beta cells are mechanistic results of dosing cells with massive non-clinical levels of statins (and even so, pitavastatin was the least “toxic” among them barely breaking 10% vs 50+% for other statins). The point is, that with smaller amounts of statins authors of the paper observed the negative effects diminish rapidly - and in practical terms, the amounts used would never reach those levels as the approved and marketed highest dose of pitavastatin tops out at 4mg daily. I’ll return to this dosing point later, but in turn when looking at the MR studies obviously we don’t see cytotoxic effects - people with alleles in the statin MOA pathway don’t suffer from poisoned pancreatic beta cells - so that can’t be the mechanism - meanwhile, all ApoB/LDL lowering alleles are associated with greater T2D propensity, not just statins, not likely they’re all cytotoxic to beta cells. If all different paths lead to the same result - lower LDL and all also lead to higher T2D risk, then it seems the common denominator is obviously not the pathway (as they’re all different!), but the low LDL. Whether you take the car (statin), train (ezetimibe), or helicopter to the beach to swim, and swimming is associated with drowning, while not being the cause of drowning, then it seems blaming the mode of transportation (car/statin) for the drowning is not justified - being twice removed! Thus neither cell-based cytotoxicity nor MR can lay the blame squarely on statins for T2D risk rather than low LDL.
Other papers rounded up by Cole amount to retrospective inquiries and associative relationships between statins and the development of NODM. That needs significant unpacking, because unfortunately those types of studies cannot establish causality for a very good reason - lower levels of LDL are associated with T2D risk INDEPENDTLY OF STATINS! See the paper below. So how do you disentagle the effects of lowering LDL leading to greater risk of T2D and statins leading to LDL - swimming is associated with drowning but swimming does not cause drowning. That’s one reason why all LLT show this kind of relationship, not just statins.
Now, statins can show higher T2D risk regardless of LDL lowering, but it seems that is confined to the high intensity statins. In which case, pitavastatin does not qualify right off the bat - it’s a moderate intensity statin. Combining this with the finding that even in those associative studies pitavastatin shows lower T2D risk increase than other statins, and it seems that the slight association in the case of pitavastatin might be entirely down to the fact that pitavastatin lowers LDL. Therefore in the absence of clear evidence that pitavastatin increases T2D risk, and plenty of outcome studies showing that it does not (including gold standard insulin clamp), I think odds are that indeed pitavastatin does not increase the risk of T2D.
This is a 2025 paper, and I’d recommend reading it rather than relying on AI summaries as in my experience AI summaries are significantly lacking.
A six-year longitudinal study identifies a statin-independent association between low LDL-cholesterol and risk of type 2 diabetes
“When stratifying LDL-C into quartiles [i.e. low (< 84 mg/dL), medium (≥ 84 to < 107 mg/dL), high (≥ 107 to < 131 mg/dL), and very high (≥ 131 mg/dL)], we observed that patients with LDL-C < 84 mg/dL had the highest risk of developing T2D. The interaction between statin therapy and T2D incidence was significant only in the very high LDL-C group, where statin users had a greater risk than non-users (p = 0.018); in the other three LDL-C groups, statin therapy did not significantly modify the association between LDL-C and T2D risk.”
“The increased risk of T2D at lower LDL-C levels appears to be independent of statin use, supporting the role of LDL-C as a potential biomarker of T2D susceptibility.”
This is the paragraph that strongly implies that pitavastatin is likely NOT responsible for elevated risk of T2D: it is NOT a high intensity statin, topping out at 4mg as a moderate intensity statin, which such statins show no elevated risk of T2D.
“When statin interaction was included in an additional multivariable model, only the very high LDL-C group (≥ 131 mg/dL) displayed a significantly elevated risk of T2D in patients on statins compared to those not taking statins (interaction term aHR 1.68, 95% CI 1.09–2.58, p = 0.018). In contrast, the interaction between statin use and T2D risk was not statistically significant in the other LDL-C groups. This finding, in other words, highlights how, while the risk of T2D increases with statin usage by a constant amount in every LDL-C group, this risk is instead different and significantly increased in the very high LDL-C group only. In fact, as can also be observed in Fig. 4, while the statin usage significantly determines an increased risk of T2D at all categories (evidenced by the confidence bands) the steepness of the line plot only deviates, although slightly, at the last category”.
All in all, I think the evidence strongly leans toward pitavastatin NOT elevating T2D risk. So, personally I am not worried about pitavastatin and A1c. However, that still leaves the fact that lower LDL increases T2D risk regardless, especially in genetically susceptible individuals. What that leads me to believe is that you really do need to combine lipid lowering and glucose lowering therapies. Just as untreated cancer witihout side effects of drugs is worse than drug treated cancer with side effects and the addition of drugs which alleviate side effects is better still, so too LLT is better than untreated high ApoB/LDL, but LLT plus glucose control drugs is better than LLT alone. Again, a carefully curated polypharmacy is superior to monotherapy.
This is why I am particularly keen on researching drug interactions - you want the optimal combinations. And when it comes to glucose control and possible toxicity I am far more worried about rapamycin than pitavastatin. I think rapamycin should be paired with glucose control (and lipid control) agents) and possibly beta cell mitochondrial protection agents such as imeglimin. ITP seems to indicate that rapamycin pairs well with glucose control drugs.