Karl - just a minor quibble but your post was about supplements and now you are complaining about meds.
What potential thing do you think that taking metformin by a non-diabetic would do?
Metformin is an okay weight loss drug and cheap as dirt. It has also been used millions of times with almost no serious side effects. Sure lactic acidosis but we stopped being overly cautious about even that over the years. And, yes, I know there are guidelines regarding surgery that I have also seen completely ignored.
There are all sorts of studies about Metformin in various situations including diabetes prevention, PCOS, metabolic syndrome and diastolic dysfunction. Also prevention of muscle atrophy during recovery and reducing fibrosis.
I don’t have diabetes but have no qualms about popping a Metformin, rybelsus and some Jardiance right now (I don’t do that). None of them interact significantly and even hypoglycemia is unlikely if added to sequentially and while keeping an eye on things. None of them really drive sugars that low.
Real patient stories - I’ve given mine, why not give yours? People do stupid things all the time but that doesn’t make using things off label necessarily a dangerous thing.
And if you have strong objections to off label use, what it is about a Rapamycin forum that interests you?
I’ve been around long enough to know that we make mistakes in medicine and interpreting data is fraught with challenges. I also feel that inferences can be made and risk benefit can be balanced. Our system focuses on reducing risk perhaps a bit too much. All of us have biases based on specialty and I’m sure that an ER doc has a certain bias formed from spending time taking care of acute problems.
Interesting how the American College of Cardiology just validated what everyone here already knew. And people here and online have been essentially working under the newer guidelines for 5 years getting all sorts of benefits because of it. Just consider the damage done in those 5 years by being too conservative about guidelines. Yes - 5 years is arbitrary but I’m thinking of my own statin use over the objections of my PCP. Now consider the MIs that you took care of over those 5 years. And balance the reduction in that with your Metformin or statin overdoses. And you aren’t taking care of the excess dementia patients created over those 5 years.
Do you think that borderline high glucose levels are just fine for your vessels and your brain just because you haven’t reached a particular cutoff?
I am lumping these together as they are all essentially medications, and they are being taken without physician oversight by people with varying amounts of knowledge.
My primary point on Metformin is that there is no evidence to support longevity benefits in non diabetics.
I take lipitor 10. I had an LDL of 140 which with no other risk factors didn’t get you a statin. Going very near vegan didn’t move the needle.
I also take Zetia 10.
My LDL is 66.
As you know, proving longevity is pretty hard when you don’t look. Heck it is pretty hard when you do look. I don’t take Metformin personally although I have. My Aic was 5.9%. Now 5.3 on Jardiance.
There is no proof that Jardiance will help in a prediabetic. I find the risk benefit works. Maybe I am wrong and gambling may not always be a thing we want to do to patients but educated extrapolated guesses can be pretty good.
I am in complete agreement with the precautions you express regarding supplements. As a data guy, I expected to see a more urgent call to exercise caution when prescription drugs are recommended. Let’s look at the contrast:
Based on reasonably good (although I expect less than complete) public data, zero deaths are reported due to supplements in a typical year. Often, when a death does occur, the FDA seizes upon the tragedy and attempts to put a ban in place. Sometimes they are successful.
In contrast, the most recent analysis by the American Society of Pharmacovigilance (ASP) estimates that 250,000 to 300,000 deaths annually are attributable to adverse drug events, including overdoses, drug interactions, allergic reactions, and medication errors. This figure positions ADEs as the 3rd leading cause of death in the U.S., surpassing deaths from stroke and respiratory disease.
To be clear, an important footnote should accompany these hundreds of thousands of annual deaths; some of these deaths occurred in very frail patients and might not have occurred in a more robust person. This footnote, however, does not put much of a dent in the overwhelming contrast between supplements and prescriptions drugs. I think you should have mentioned that.
So then you are taking a statin for good reason. You’re not someone with an LDL of 80 who starts a statin on their own to get LDL to 40 without evidence that it will help and at risk of causing diabetes.
@RobTuck Agree with your assessment that supplements in general are much safer than medications. I’m not sure I’m as confident that we get reliable feedback on bad outcomes of supplements.
There is certainly a fair amount people that go from supplement use to off label and non prescription use of prescription medications without fully understanding what they are taking.
Eh? There’s a bunch of studies showing a variety of benefits like increasing insulin sensitivity and lowering odds of progressing to full blown T2DM for SGLT2i agents. But regarding empagliflozin specifically we should have some answers at the end of this year:
Use of Empagliflozin to Treat Prediabetes
You would need to have the indication specify prediabetes for empagliflozin to get more studies financed, but even so, in clinical use physicians on their own do prescribe empa for prediabetes.
Depends on what level of evidence you need, but empagliflozin in prediabetes seems a reasonable bet.
To get really specific, my A1C normalized during a statin holiday and weight loss. I’m not obese (the trial looks like it is in obese patients) and my insulin is 3.3. So for me with a history of prediabetes, there is not likely any proof.
And what is out there to date would not be considered proof. Evidence perhaps but not proof. Semantics perhaps but I suspect most doctors wouldn’t prescribe even with a clear pre diabetic picture and no insurance would pay for it. My doc wouldn’t.
As far as using a statin to go from LDL 80 to 40 - I suspect if there was a trial it would show a reduction in CV disease. It might be a small effect and take years and a large population to demonstrate it but I would bet money it would show it. And if A1C was watched and used as a stóp point, there would be insignificant harm done.
We will not see a trial because the trial would be expensive and no one makes enough $ to pay for it. A shame for sure. It would be really nice to know if driving LDL low would help with dementia. I think we can infer from high risk patients that CV gets better down to at least LDL 55. But dementia is a big unknown.
A study for reducing LDL from 80 to 40 has not been done exactly but close. The median LDL-C in Repatha’s trial was 92. 6,600 had LDL-C between 70-80 (had to have LDL-C of 70 or higher). Everyone was on a statin or some other lipid lowering drug. The trial was so successful it ended early due to ethical concerns. The risk reduction in these trials is always low because they only last a few years. But if you extend it over a lifetime then a 1.5% reduction in risk can easily be 25% or higher.
A statin got my LDL-C to 80. But Repatha lowered it to 27.
Thanks for that reference. The question was specifically about statins and the potential harm of diabetes which repatha does not have. And presumably this study was in high-risk patients. But it is a good example of how we can make educated inferences and be correct most of the time.
Aspirin is of course instructive on balancing harm. Overall is felt to be net negative on low risk people. But it also isn’t providing a benefit 20 years down the line. By mechanism, it works just the week you take it whereas cholesterol lowering benefits for life. Colon polyps is another story and I’m not sure if this was ever accounted for in the study. In other words, while aspirin bleeds overwhelms the cardiac benefit, does it overwhelm polyps + cardiac benefit?
Similar to statins where both CVD and dementia are benefits. Studies just look at CVD. And dementia results are much more confusing.
I don’t think there is any cause for concern with statins and diabetes. I suppose it is similar to rapamycin. If you are predisposed it is possible that it could put you over threshold from pre-diabetes to diabetes. But that can be managed. There is actually a new study (VESALIUS-CV) for primary care patients with a lower risk profile with similarly good results. I worry about my A1C but I didn’t stop using by statin when I started Repatha.
But the flip side of what you are saying in here is actually in agreement with my point about supplements. so basically, there is no death, and no risk of severe injury taking a substance (or a group of substances) then clearly that in itself means such substance is not all that useful and as such can’t do any bad and by default it can’t do much good either, and by useless I mean it is not needed (since we get most nutrients from diets and other activities) whereas the case with drugs is totally opposite, since you can easily hurt yourself by abusing with them which is to say they are very powerful substances, thus if properly used could indeed be very useful/helpful.
Of course, I get your overall point and do agree with you that one should always be very cautious when taking or mixing drugs.
A complicated discussion for sure but I don’t think it follows that a substance that can’t kill or severely injure you can’t help you.
Another layer in here goes to agency. Most people take prescribed drugs because an expert tells them to whereas most people take supplements because of a deliberative decision to learn about them and seek their purported benefits if justified by what they learn. Because of this agency, they feel responsible for taking the supplements correctly. (My focus is main effects and not the outliers that make newspaper headlines.) I know of no study but I would wager that the average supplement user can tell you more about what they are taking and how it works than can the average Rx user. In contrast to this, most modern prescription drugs consist of a single engineered molecule that exerts a known and often powerful effect on some biological function whereas supplements often consist of a family of related molecules and generally exert more modest effects.
There isn’t much that I disagree, but my point is that in very near term the supplement euphoria/bubble will burst (it has already started to burst as seen from many longevity influencers trimming their supplement stacks as of late) which is to say it becomes mainstream that you only benefit from taking a supplement if your body is deficient in. The rest of them are simply expensive excrements lol.
Beth, same here, very nice app BUT they also sell products and I’m sure they are high quality. I also noted the medicore ratings for my main sources NOW and BulkSupplements. But my essential items, like fish oil and astazanthin, I buy a common brand and a high priced brand for insurance. None of my high priced brands were listed. Why would they “advertise” or even acknowledge a direct competitor? They’re trying to make a buck, which is not odd at all. I still am using them, I scanned my supplements then imported that into a ChatGPT AI and that AI is where I manage my list. But for a quick barcode id/info on common brands, they’re tops.
I thought you were a guidelines person. They note the small diabetes risk but state that “the benefits of reducing ASCVD events greatly outweigh the risks.”
The Scientific Statement from the American Heart Association presents evidence for a minimal risk (0.2% per year) of developing newly diagnosed diabetes mellitus on statin therapy, which is predominately among patients with pre-existing risk factors for developing diabetes (e.g. adults with pre-diabetes/metabolic syndrome). The mechanisms of the diabetogenic effect of statins remain unclear. The JUPITER Trial13,19 was the first prospective study evaluating statins and newly diagnosed diabetes mellitus among 17,802 patients without known diabetes at the beginning of the study. In the rosuvastatin group 0.6% more patients were reported to have diabetes by their physician over a median of 1.9 years with a small but statistically significant HbA1c difference of median values of 5.9% for rosuvastatin vs. 5.8% for placebo, with no significant difference in fasting glucose.
A large meta-analysis with pooled data of 32,572 patients showed over a median of 4.9 years on statin therapy that 2 cases of diabetes occurred per 1000 patient-years of treatment and 6.5 cardiovascular events (stroke, myocardial infarction, revascularization) per 1000 patient-years were prevented20. Additionally, patients with diabetes on statin-therapy have a negligible increase in HbA1c as shown in AFORRD21 (atorvastatin 20mg vs. placebo; N = 800) and CARDS (atorvastatin 10mg daily vs. placebo N = 2,838) 22,23 RCTs with increases in HbA1c of 0.3% and 0.1% respectively at 4 years.
The Scientific Statement from the American Heart Association raises the question if statin therapy accelerates the development of diabetes in those patients with metabolic syndrome, who would otherwise likely develop it. Among patients on high-intensity statin with risk factors for diabetes, it is prudent to continue aggressive prevention with lifestyle modification (weight loss if indicated and better exercise habits) and periodic screening for diabetes.
You’re talking oranges when I’m talking apples.
I was talking about people on this forum who take statins to lower cholesterol when they already have normal cholesterol levels. There are no guidelines for this. Is the benefit of the this worth the risk of worsening insulin sensitivity?
I understand from your posts that you do not like statins. So be it; you’re welcome to your opinion, but it goes against the preponderance of medical opinion.
Every medication that I take has some adverse consequences for some people. We must always weigh the benefits vs. the negative risks.
“Cardiovascular protection conferred by statins vastly offsets the modest diabetes risk.”
Anyone is welcome to read the papers I have linked and draw their own conclusions.
This is only a small portion of the references I have about statins and diabetes.
The references are from Claude, ChatGPT, and Gemini.
“The best evidence comes from large randomized trials and meta-analyses. The key point is that statins do appear to increase the risk of new-onset diabetes slightly, but the absolute risk is small, and varies by dose and type.”
The Net Benefit Framing
The consensus across recent reviews is that the cardiovascular protection conferred by statins vastly offsets the modest diabetes risk, and this risk should not deter initiation of guideline-recommended therapy. PubMed Central The 2024 CTT analysis specifically notes that any theoretical adverse cardiovascular effects arising from the small glycemia increases are already accounted for within the overall cardiovascular risk reduction seen in the trials. PubMed
A 2024 Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis in The Lancet Diabetes & Endocrinology confirms that while statins slightly increase the risk of new-onset diabetes—by 10% for low-intensity and 36% for high-intensity—the cardiovascular benefits significantly outweigh this risk. The risk is highest for individuals with pre-existing high blood sugar, as statins may cause a small increase in HbA1c that triggers an earlier diagnosis, particularly at higher doses. Read the full study in The Lancet
Overall Risk Magnitude
The evidence is consistent but the magnitude depends heavily on study design. RCT-based meta-analyses tend to show more modest effects than observational studies, which capture longer exposures and real-world populations:
Bottom line: Absolute risk of statin-attributable diabetes in a metabolically healthy person is quite small. The risk is real but concentrated in those already near the diabetic threshold, escalates with dose intensity, and varies meaningfully by agent — with rosuvastatin and high-dose atorvastatin at the higher end, and pravastatin and pitavastatin at the lower end.
Bottom line (causal estimate)
Best estimate (RCT-based):
~9–12% relative increase
~0.1–0.3% per year absolute excess risk
Roughly 1 additional diabetes case per 200–300 users over ~4 years