That is what I will probably do.
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Insulin sensitivity was decreased by 24% and insulin secretion by 12% in individuals on statin treatment (at FPG and 2hPG <5.0 mmol/l) compared with individuals without statin treatment (p < 0.01). Decreases in insulin sensitivity and insulin secretion were dose dependent for simvastatin and atorvastatin.
Conclusions/interpretation: Statin treatment increased the risk of type 2 diabetes by 46%, attributable to decreases in insulin sensitivity and insulin secretion.
Correct, the increased risk of diabetes from statins is primarily driven by the dual effects of insulin resistance and pancreatic beta-cell dysfunction.
So 2:1 insulin resistance vs secretion if you can compare in that way. I guess the issue for me is the reversibility of all this. Secretion, of it truly is a pancreatic toxic effect would seem to be irreversible, but everything else would seem more likely to be reversible.
As we all know, the diagnosis of diabetes isn’t really flipping s switch. It is crossing a line that you can come back from at least in regards to the outcome of blood sugars and end organ damage.
Plenty of people lose weight and then have normal blood sugars for a very long time. The sensitivity can be fixed by changing body composition.
Secretion would seem to be significantly less modifiable.
This study had a mean homa-ir of 2.0 without statins which would seem to be a fairly high risk population.
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For someone who is fit and metabolically healthy (probably most people here) the risk of developing diabetes due to a low dose stain is extremely low even over a very long time frame
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I can’t take metformin, so I am always looking for ways to lower my glucose levels, as I am always on the borderline of pre-type II diabetes.
I switched from atorvastatin to pitavastatin, and my A1c dropped from 5.7 to 5.4. No other changes to my diet or supplement list occurred during the time I started pitavistaten and the blood test.
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You don’t have to worry about pitavastatin affecting insulin sensitivity or any aspect of glucose control in general. There are all sorts of studies out there (including very low value stuff like the FAERS cited by Cole - FAERS as you know is just a database of reports from patients, and this of course subject to all sorts of statistical anomalies and not validated in any way).
For insulin resistance, we have the gold standard of using the euglycemic hyperinsulinemic clamp. There’s nothig that directly measures insulin like this and not really subject to dispute.
Here we have a six-month, double-blind, randomized, placebo-controlled trial - again top notch trial design (and using a euglycemic hyperinsulinemic clamp). At a top notch institution - academic clinical research center in Boston, Massachusetts.
Effects of Pitavastatin on Insulin Sensitivity and Liver Fat: A Randomized Clinical Trial
“Pitavastatin showed no effect on endogenous glucose production (Δ Ra glucose 0.07 ± 0.07 vs 0.04 ± 0.07 mg/kg/min, pitavastatin vs placebo, P = 0.76) or insulin-stimulated glucose uptake during “low dose” (Δ M 0.1 ± 0.1 vs −0.3 ± 0.2 mg/kg/min, P = 0.11) and “high dose” (Δ M −0.5 ± 0.3 vs −0.7 ± 0.4 mg/kg/min, P = 0.70) euglycemic hyperinsulinemic clamps. There was also no effect of pitavastatin on fasting glucose, HbA1c, and 2-hour glucose after 75-g glucose challenge. There was also no change in liver fat fraction (−1 ± 1 vs −0 ± 1%, P = 0.56).”
Done and done. I could post scads of papers to the same effect of pitavastatin not causing NODM, either against a placebo or another statin and have done so in the past - but there’s no point here, as this study is as good as it gets. Do it once, but do it right.
Now, it won’t help reduce your liver fat, but you can do that by losing weight. The bottom line is that you don’t have to worry about pitavastatin affecting your insulin sensitivity or any aspect of glucose control.
As a doctor you might be encouraged by another research doctor who had issues with A1c on another statin and elected to substitute that statin with pitavastatin to bring down his A1c - and pitavastatin did exactly that. I posted this video in another thread:
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Or you take retatrutide which slashes liver fat by 90% 
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Also if you’re taking Pitavastatin and combine with GLP1, SGLT2, or/and Acarbose/Metformin/Berberine, you’re almost surely not going to have to worry about insulin sensitivity. You probably wouldn’t even without them if other good lifestyle factors are in place.
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This trial doesn’t affect my conclusion at all. As I’ve said, I’ve reviewed almost every single RCT on pitavastatin.
The phenomenon you mentioned is something I’ve already observed across multiple RCTs. However, it unfortunately does not change the fact that pitavastatin carries the same risk of new-onset diabetes (NOD) as other statins.
The underlying reason is straightforward: pitavastatin directly damages pancreatic beta-cells. Other factors—like low CoQ10, SIRT6 inhibition, altered gut microbiota, and disrupted bile acid metabolism—are just minor contributors to the overall risk of NOD.
Furthermore, the risk of statin-induced NOD has been severely underestimated due to various confounding issues. The damage statins cause to the pancreas is cumulative over time. Papers looking into the correlation between duration of statin use and NOD have shown that for those using them for less than 2 years, the increase in NOD risk is not statistically significant. The highest risk of NOD is seen in those reaching or exceeding the 2-year mark.
Results: A higher prevalence of elevated HbA1c (PD = 0.065; 95% CI: 0.002, 0.129, P = 0.045) occurred among nondiabetic incident users of statins. Additionally, statin users had a higher risk of developing NOD (AHR = 2.20; 95% CI: 1.35, 3.58, P = 0.002). Those taking statins for 2 years or longer (AHR = 3.33; 95% CI: 1.84, 6.01, P < 0.001) were at the greatest risk of developing NOD; no differences were observed by statin class or intensity of dose.
So, a 6-month RCT doesn’t change my conclusion in the slightest.
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Of course, there is a solution: genotyping before starting a statin. This allows patients to determine whether they are in a high-risk or low-risk category, thereby enabling a better assessment of the risk-benefit ratio.
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Of course, AI disagrees with you. From Gemini
Pitavastatin (commonly known by the brand name Livalo) interacts with the pancreas primarily in two distinct medical contexts: as a potential preventative shield against inflammation and cancer, and in its neutral or favorable impact on glucose regulation compared to other statins.
- Protection Against Pancreatitis and Pancreatic Cancer
Recent groundbreaking medical studies have revealed that pitavastatin may play a significant role in safeguarding pancreatic health from severe inflammatory conditions:
Blocking Inflammatory Pathways: Researchers at Harvard University identified that pitavastatin effectively suppresses the production of Interleukin-33 (IL-33). IL-33 is a primary signaling protein responsible for driving the chronic, cancer-prone inflammation that targets the pancreas.
Lowering Chronic Pancreatitis Risk: According to an epidemiological study published in Nature Communications, analysis of global health records involving over 200 million people demonstrated that patients taking pitavastatin had a significantly lower risk of developing chronic pancreatitis.
Reducing Pancreatic Cancer Risk: The same study revealed a marked reduction in pancreatic cancer development among pitavastatin users. By disrupting the underlying chronic inflammatory environment, the medication prevents pre-cancerous cells from advancing into aggressive malignancies.
Synergistic Cancer Therapy: Laboratory trials published in Environmental Toxicology indicate that pitavastatin works synergistically with standard chemotherapies (like gemcitabine) and metabolic medications (like metformin) to promote cell death (apoptosis) and slow down the migration of existing pancreatic cancer cells.
- Blood Sugar Management and New-Onset Diabetes
While some cholesterol-lowering medications (statins) can stress the endocrine function of the pancreas and increase the risk of developing type 2 diabetes, pitavastatin stands out for its favorable profile:
Favorable Glucose Homeostasis: Data compiled by Springer Link shows that pitavastatin has a significantly lower risk of causing New-Onset Diabetes Mellitus (NODM) compared to other high-potency statins like atorvastatin or rosuvastatin.
Preserving Beta-Cell Function: Pitavastatin does not impair peripheral insulin sensitivity to the same extent as its counterparts, allowing the insulin-secreting beta cells in the pancreas to function normally without overcompensating.
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maybe you’re not noticing anything because you said it was long expired…!
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It’s definitely possible, but they are apparently still mostly effective, so??
I’ll be finding out as I’m going to start taking 1mg daily and then I’ll ramp up if all goes well.
how would you know they are still effective? the only way to tell would be blood draws. most medicines lose potency rather quickly and if they are “long expired” (what ever that is) they may be ineffective at best. why don’t you get a new script?
On the question of increased diabetes risk with statin use, I think we need to put the various study results into perspective. I asked ChatGPT the following:
“How is incidence of NOMD calculated in this context? Is it a question of blood glucose and insulin levels crossing a threshold, or is there permanent damage to the pancreas necessitating exogenous insulin?”
The bot’s answer below. My take on this is that what we’re really talking about is a worsening of insulin resistance, which in those with existing IR can push them over the clinical definition of diabetes, and which should still be reversible with medications and lifestyle interventions.
ChatGPT:
Good question — and this is where “new-onset diabetes (NODM)” in statin studies often gets misunderstood.
## 1. What “NODM” actually means in these studies
In virtually all statin and cardiovascular outcome studies, NODM does not mean pancreatic failure or insulin dependence.
It is usually defined using standard diagnostic thresholds, such as:
- Fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dL), or
- HbA1c ≥ 6.5%, or
- 2-hour OGTT glucose ≥ 11.1 mmol/L, or
- A clinical diagnosis recorded in medical records, often including:
- starting diabetes medication (metformin, etc.)
So it is fundamentally a biochemical/diagnostic threshold event, not a structural disease marker.
## 2. What it does not mean
NODM in these datasets does NOT imply:
- permanent pancreatic “damage”
- loss of insulin production requiring insulin therapy
- beta-cell destruction (like type 1 diabetes)
- irreversible metabolic failure at onset
Most people classified as NODM:
- are initially treated with lifestyle ± metformin
- often have mild or early type 2 diabetes
- retain substantial endogenous insulin production
## 3. What is actually happening biologically
In the context of statins (including pitavastatin, atorvastatin, etc.), the mechanism is believed to be:
- mild worsening of insulin sensitivity (muscle and liver)
- slightly increased hepatic glucose output
- small changes in insulin secretion dynamics in susceptible individuals
So statin-associated NODM is usually:
a shift across a diagnostic threshold in predisposed individuals, not a sudden biological switch to insulin dependence
## 4. Why this matters for interpreting studies like pitavastatin papers
When you see:
- “new-onset diabetes increased by X%”
that typically means:
more people crossed a lab or diagnostic cutoff during follow-up
It does not mean:
- more people developed clinically severe diabetes
- more people required insulin
- more people had pancreatic dysfunction
That distinction is why:
- absolute risk increases are small
- and many cases are reversible or mild early T2D
## 5. Why statins look like they “cause diabetes”
A key nuance:
Many people classified as NODM in statin trials were likely:
- already in pre-diabetic range at baseline
- progressing slowly anyway
Statins may:
- slightly accelerate the timing of crossing the threshold
- not necessarily create diabetes de novo
This is supported by analyses showing the strongest risk in people with:
- higher baseline fasting glucose
- higher BMI
- metabolic syndrome features
## 6. Does any of this involve insulin dependence?
Very rarely in these datasets.
In real-world terms:
- statin-associated diabetes is overwhelmingly type 2 diabetes phenotype
- insulin use at diagnosis is uncommon
- pancreatic “failure” is not the mechanism
If insulin is eventually needed, it is because:
- the person has progressive type 2 diabetes over time, not because of acute beta-cell loss from the statin
## 7. Bringing it back to pitavastatin
So when studies report:
- lower NODM risk with pitavastatin
what they really mean is:
fewer people crossed the biochemical diagnostic threshold for type 2 diabetes during follow-up
not:
pitavastatin protects pancreatic beta cells from destruction
Bottom line
- NODM = diagnostic threshold crossing (glucose/HbA1c/recorded diagnosis)
- NOT pancreatic failure
- NOT insulin dependence
- Usually represents early or mild type 2 diabetes in predisposed individuals
- Statin effect = small metabolic shift + threshold acceleration in some people
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Pitavastatin slows biological aging in HIV patients for whatever that’s worth
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The REPRIEVE trial also showed a massive jump in new-onset diabetes, which was severely underreported. If you look at the epigenetic aging sub-study, the anti-aging effect is actually minuscule. Plus, due to a pre-existing bias to find benefits, the data actually glosses over some pretty concerning outcomes. Fortunately, I didn’t see this issue in RCTs for non-HIV patients. Bottom line, I just hope people carefully weigh the risk-reward ratio based on their own situation.
https://www.nejm.org/doi/full/10.1056/NEJMoa2304146
Muscle-related symptoms occurred in 91 participants (2.3%) in the pitavastatin group and in 53 (1.4%) in the placebo group; diabetes mellitus occurred in 206 participants (5.3%) and in 155 (4.0%), respectively.
https://academic.oup.com/cid/article/81/6/e560/8166545?login=false
Median chronological age was 57.0 (Q1, Q3: 56, 58) years and 100% of participants demonstrated epigenetic age acceleration, measured by the difference in PCGrimAge and chronological age (median difference 7.08 years [Q1, Q3: 4.69, 9.64]) at entry. Over 24 months, PCGrimAge remained accelerated with no significant differences between treatment arms (P = .89). However, the median pace of aging by the DunedinPACE increased in the placebo arm (0.036, Q1, Q3 [−0.018, 0.10], P = .021) but not in the pitavastatin arm (0.001, Q1, Q3 [−0.031, 0.036], [P = .77]), treatment group difference (P = .049).
It’s worth noting that prophylactic use in HIV patients significantly reduces cardiovascular risk, and there’s a pretty high probability that this effect translates to healthy individuals as well. Bottom line, guys—just weigh your own risk-reward ratio.
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I’ve been on high dose 80-40mg atorvastatin for 4 years and my A1c and blood glucose have stayed virtually unchanged. Does pitavastatin work via the mevalonate pathway or by some other pathway? If mevalonate then it’s affects will be similar to other statins, no?
I think if you’re on a lifelong therapy like a statin, it makes sense to do some self-experimentation and see what works for you. I don’t know how to quantify it, but there seems to be plenty of individual variation. For me, 10mg Rosuvastatin per day causes no noticeable side effects, and no change in my HBA1C (stable at 4.9-5.1%), but apparently other people have more severe reactions. Since we have plenty of options available, it makes sense to take a rational approach and see what works best for yourself (assuming you are otherwise health and taking this for prevention etc).
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I’m surprised to see so many HbA1c when as far as I’ve heard it’s not the most accurate measure of early insulin resistance. OGTT for instance is considered better.
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