#1

I have looked at some of the comments on elevated blood sugar but don’t see what I’m looking for.
Is the rise (for most people) a permanant type thing or does it subside until next dose? I am taking 5mg with 12 oz GFJ every 10 days. My A1C was 5.5 at my last labs check and my fasting BS was 96. (I was on the 5mg/10days only for 2 cycles)… I bought a glucose meter to kind of see what it says and just got it at the tail end of my 10 day cycle. (I dose again this friday). If the rise is just transitory then I’m not too worried about that. if it’s more permanant then I’ll need to add something (metformin?) depending on what my meter results give me over the course of my regimen.

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#2

I take 3 or 4 with GFJ every 2 weeks. So much less than you. I have 5 (2week) periods where I tried to do it every day. I got most of them. Just eyeballing I would say the first 3 or 4 days is in the high ninetys. The rest are usually below ninety tailing down to mid eightys.

I tried metformin for the first few days, then empag. It got my HBA1c down to 5.2. I don’t really like either drug and now I’m doing nothing. When I’m less busy I’ll probably start up again with empag.

#3

my BS has always been in the upper 90’s. (for the last 30 yrs) as it was tested due to my job requirements. they were always fasting values. I’m pushing 66 yrs old and started dosing about 3+ mo. ago but stopped for awhile due to surgery. just started back up about 4 wks ago. I see a lot of comments on elevated BS so was wondering if it’s just transitory for most people for a few days after dosing or more permanant.

#4

I have been taking rapamycin for almost 5 years now - but have only monitored blood glucose levels with a CGM (continuous glucose monitor) for 3 or 4 periods (of two weeks each) during that time. Generally when I’m using the CGM I’m also testing out an SGLT2 inhibitor or acarbose as well as taking rapamycin. I’ve noticed no increase in blood sugar at all. But - its a small sample size. As CGMs get cheaper I might wear it more often and be able to provide better data, but thats all I have right now.

I think rapamycin typically only increases blood sugar if you’ve been taking higher doses of rapamycin for longer periods of time…

Please report on your own results as you move forward.

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#5

@rapadmin. will do after a couple of my cycles.

#6

The question of how much and how long on elevation of blood glucose - it’s pretty likely to a small degree with most people. For myself, a rise of HbA1C by 0.5%.

However, anticipating this, and recognizing that drugs like SGLT2-i’s look to be great longevity drugs … acarbose probably so also … It is very common to just do these as part of a longevity protocol with Rapamycin.

I’m not favoring metformin, and don’t have any non-diabetics on it. Overall sarcopenia is its own risk to harm longevity, and metformin increases this. I think we have better choices currently.
If you have any weight to lose, add a GLP-1 … also great longevity drug.

So I’d generally not think about having someone on Rapamycin without thinking about these 3 classes of medications - also Telmisartan at least 80 mg for PPAR effects will help insulin sensitivity.

There are lots of options to allow optimization of insulin sensitivity and glucose. Naturally seek advice from an expert on what is best for your situation.

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#7

from a quick look, it seems that a GLP-1 would be a good thing for me to look at as my quick read said that GLP1’s are better for higher eGFR’s and SGLT2 for eGFR below 60. I’ll have to do some more reading though. My eGfr tends to be in the mid 90’s.

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#8

Is this claim based on its mechanism of action or are you seeing noticeable effects on insulin sensitivity with telmisartan in your practise? I know that its PPARgamma activation ability should help with insulin sensitivity, but it’s a relative mild PPARgamma activator.

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#9

I’d look at the following … essentially 160 mg is better … that’s what I’m doing these days. I don’t have enough data from patients to have any basis to speak, so need to rely on published data.

A reasonable AI review on this is:
Telmisartan, an angiotensin II receptor blocker (ARB), is known for its ability to activate peroxisome proliferator-activated receptor-gamma (PPAR-γ), which contributes to its metabolic and anti-inflammatory effects. This activation is dose-dependent and typically occurs at higher doses than those used for blood pressure control.

For PPAR-γ activation, telmisartan is effective at doses of 80 mg and 160 mg per day. Studies have shown that these higher doses can induce PPAR-γ target genes, particularly in patients with metabolic syndrome, suggesting enhanced efficacy in activating PPAR-γ at these levels. This activation is associated with improved insulin sensitivity, lipid metabolism, and anti-inflammatory effects.

Additionally, telmisartan’s role as a PPAR-γ/α dual agonist has been explored in conditions like nonalcoholic fatty liver disease (NAFLD), where it may offer benefits by enhancing insulin sensitivity and lipid metabolism. The dual activation of PPAR-γ and PPAR-α could provide therapeutic advantages in conditions characterized by metabolic dysregulation.

It is important to note that while telmisartan’s PPAR-activating properties are well-documented, its use specifically for PPAR activation is not an FDA-approved indication. The decision to use higher doses for this purpose should be based on individual patient factors and potential risks versus benefits. Always consider patient-specific factors and clinical considerations when determining the appropriate dosage.

References

  1. Telmisartan inhibits AGE-induced C-reactive protein production through downregulation of the receptor for AGE via peroxisome proliferator-activated receptor-gamma activation
    Diabetologia 2006

A unique beneficial aspect of telmisartan is indicated: it may work as an anti-inflammatory agent against AGE by suppressing RAGE expression via PPAR-γ activation in the liver and may play a protective role in vascular injury in diabetes.

  1. Telmisartan-Induced Inhibition of Vascular Cell Proliferation Beyond Angiotensin Receptor Blockade and Peroxisome Proliferator-Activated Receptor-γ Activation HYPERTENSION
    Yamamoto et al. 2009
    The antiproliferative effects of telmisartan in the absence of exogenously supplemented angiotensin II involve more than just AT1 receptor blockade and do not require activation of PPARγ.

  2. High-Dose Treatment With Telmisartan Induces Monocytic Peroxisome Proliferator-Activated Receptor-&ggr; Target Genes in Patients With the Metabolic Syndrome. HYPERTENSION
    Bähr et al. 2011
    Analysis of serum interleukin 6 levels and monocytic PPAR&ggr; target gene expression in drug-naïve patients with the metabolic syndrome implicate that the angiotensin type 1 receptor blocker telmisartan activates PPAR; in circulating monocytes of patients withThe metabolic syndrome.

  3. An insight into the role of telmisartan as PPAR‐γ/α dual activator in the management of nonalcoholic fatty liver disease Devan et al. 2021
    The possible mechanism of telmisartan, a typical angiotensin receptor blocker with excellent safety and pharmacokinetic profile, as a PPAR‐γ/α dual agonist in the treatment of NAFLD is discussed.

Telmisartan, an Angiotensin II Type 1 Receptor Blocker, Inhibits Advanced Glycation End-product (AGE)-induced Monocyte Chemoattractant Protein-1 Expression in Mesangial Cells through Downregulation of Receptor for AGEs via Peroxisome Proliferator-activated Receptor-γ Activation
Matsui et al. 2007
A unique benefit of telmisartan is demonstrated in that it may function as an anti-inflammatory agent against AGEs via PPAR-γ activation and may play a protective role in diabetic nephropathy.

  1. Telmisartan ameliorates adipoR1 and adipoR2 expression via PPAR-γ activation in the coronary artery and VSMCs. Shen et al. 2017
    It is demonstrated that telmisartan effectively ameliorated coronary insulin resistance and inflammation in diabetic rats and upregulated AdipoR1/R2 expression via activation of PPAR-γ in the coronary artery
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#10

At 6mg and 4mg my fasting glucose went >100 and takes 4-6 weeks to come back down. At 2mg a week there’s no effect.

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#11

@shady. 6mg/4mg of what? rapamycin? 2mg a week probably isn’t going to do anything for you.

#12

@sudiki yes Rapamycin. Dr. Reddy’s. Taken with a fat containing meal. Usually olive oil.

There’s no great human evidence for 6mg a week or any other dosing protocol so I’m not sure that you can conclude that 2mg a week isn’t a good dose. 6mg being optimal simply because the masses take it isn’t really scientific evidence. On the contrary, taking a prolongevity drug at a dose that renders me pre-diabetic despite a low carb diet and excellent A1C and HOMA-IR off the drug seems counterproductive.

The degree of MTORC inhibition predicts the response. Easy to assume that will vary among people despite similar doses. A fair amount of data supports over inhibition with crossover to MTORC2 as driving the metabolic side effects of rapamycin. To me, elevated FPG is a convenient marker of said inhibition.

Several theories why I could be a bit hyper responsive to it.

  • somewhat young (39), low carb diet, muscular and lean. 180lbs, 7-8% body fat. AmpK is probably rather active already and unlikely to have hyperactive mTOR due to being relatively young and without underlying metabolic pathology
  • other things in my diet that also inhibit mTOR. Green tea, fasting, turmeric, C-15, etc. compounded effect?
  • Dr. Reddy formulation overdosed?
  • absorption or metabolism kinetics unique to me? CYP3A4 slower than typical?
  • beta cell toxicity vs insulin resistance?

Nonetheless, we know diabetes is bad for you so I prefer to not pharmacologically induce it. I’m aware of benevolent pseudo-DM but this is induced upon refeeding following fasting. I’m not convinced that my Rapa response is synonymous as my FPG stays >100 despite essentially 0 carbs. It’s either an increase in gluconeogenesis, insulin resistance, or beta cell toxicity. I believe the former or the latter because my insulin drops when on higher doses rather than rises as you’d see with insulin resistance.

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#13

I base my comment on the fact that many people here have their rapamycin levels lab checked after dosing. Until proven wrong I stand on my comment and wouldn’t even bother dosing at all if I were only going to do 2mg/wk. 2mg/wk “might” be beneficial for someone your age but I’m 66 and I don’t have as much time to let it work decades like you do for longevity purposes. I dose 5mg 1 hr after 12 oz GFJ every 10 days which puts me at around a 15mg dose effect. (or higher). I don’t have any side effects at that dose that I know of except for maybe some extra pimples/boils but I’ve always had them. My glucose hasn’t done anything strange compared to my previous readings (I had labs done twice yearly due to my job req.)

#14

@sudiki that’s great that you feel that plan is best for you. Your claim that “2mg a week probably isn’t going to do anything for you” remains baseless. We have no idea what the serum target drug level is for longevity purposes. Of the limited data we do have, PEARL, they looked at essentially 1.5 and 3mg with my dose falling in the middle. It certainly didn’t show harm at those doses and perhaps there would be more benefit if carried out longer.

Also drug levels will vary widely between individuals. For all we know, you and I could have the same drug level due to differences in drug absorption, manufacturer, CYP polymorphisms, other meds/supplements, etc. Regardless, I’m not going to belabor the point that none of us know the optimal dose for longevity yet alone serum levels for said outcome. That should be obvious.

The 1st rule of medicine is to do no harm. Rapa at higher doses consistently elevates my FPG and we know that is detrimental in most if not all settings. I’m more confident (for myself) in taking a lower dose and not suffering metabolic side effects. I plan to trial 3mg and also check serum drug levels, but until then 2mg is a reasonable dose for me.

#15

I intend to do twice weekly blood tests when I next take rapamycin. I may also wear a CGM. I think what happens is that there is temporary insulin resistance from the dosing. The body will then adjust to increase insulin levels, but that comes down again.

Only one of the labs that I use tests for Insulin so I don’t have good enough records to say what the timing is of all of this. However, I intend using this particular lab for every test next time.

I am currently taking a high dose of rapamycin (last was 16mg with multiplier =~50mg), but no more frequently than every 42 days. In fact my last dose was on 28th July. I was waiting to clear some inflammation which I think has now cleared, but want at least a baseline test from the lab that does the broad range (which is on Tuesday) before running this again.

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#16

@John_Hemming here is Blagosklonny’s paper on this point

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#17

@Joseph_Lavelle I’ve read this paper and numerous others regarding Rapa and insulin resistance. Difference being starvation diabetes presents with low FPG but insulin resistance when challenged with carbs. Ie refeeding or a GTT. Physiologically this makes perfect sense and is beneficial. Rapa, at least in me, elevates FPG and glucose response to a carb challenge. More consistent with a DM2 picture than a benign process. Could it still be benign? It could but we know there’s a risk of progression to DM2 with Rapa and it still warrants caution.

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#18

@Shady its a good point. I agree we should not assume high blood sugar is fine just because it is caused by rapamycin. Blagosklonny says to pair rapamycin with metformin. Even if it is explainable I would worry about the many downstream detriments of high blood sugar.

“It was discussed that in theory the most rational combinations with rapamycin are mild calorie and fat restriction, physical exercise and metformin [52]. Metformin may in theory counteract rapamycin-induced gluconeogenesis in the liver.”

I do not seem to have this side effect so I haven’t experimented on it.

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#19

I do agree on this. High glucose causes the mitochondria to create more damage to mtDNA. I have not used a CGM since early 2023, but will probably engage a CGM around my next rapamycin dose. However, I had managed to get my peaks below the polyol pathway limit (about 8 mmol/l) which I consider to be a good level (around 140 in US units).

Previously I was peaking at 10mmol/l. (180)

I am tempted by the idea of running a CGM for a few weeks around the next dose. However, I find CGMs quite irritating and at times knock them off their location on error.

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#20

@shady. you are cherry picking to support your stance by quoting me yet again; {Your claim that “2mg a week probably isn’t going to do anything for you” remains baseless.}. I said in my follow on post that it might be beneficial for someone younger like you that has decades to use it at a low dose rate.

How about we leave it at that and you do your thing and I’ll do mine.

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