Starting Rapamycin if pre-diabetic?

Have read here that you should be in good health metabolically before starting Rapamycin. Would appreciate input: with this profile is it OK to start Rapamycin?

My A1C is 5.8. It has been at that level since 2017, perhaps even earlier. I am sure that it is genetic. BMI is 19.5; daily exercise, careful diet, healthy, but genetic profile suggests risk for high glucose and also cardio disease. (But heart health is good and lipids are where they need to be). I take Metformin, Repatha ad Ezitemibe.

Would appreciate guidance!

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With Rapamycin there are always questions as to how frequently to take it. It is known to increase blood glucose levels.

I am someone who argues for a less frequent taking of Rapamycin, there is an argument that there is a benefit to mitochondrial health each time it is taken which may plateau at a given frequency.

However, it does give the option of taking it and then waiting a while and doing another blood test.

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Some people have higher blood glucose on rapa. I had a HbA1c of 5.8 up from 5.6 after I started. I use periodic metformin and berberine plus zero processed food, added sugar, or bread / pasta / rice. I found Akkermansia to be a huge help, dropping my HbA1c to 5.0. At that same time I switched to a 2 week rapa cycle with 1 week off every month. So that may have contributed to the lower HbA1c.

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Thanks so much: very helpful. What brand of Akkermansia do you use?

Pendulum. It’s expensive so I’ve stopped taking it (after 3 months) to see if I continue to get a benefit afterwards. I may have to restart or cycle it periodically if my HbA1c goes back up.


I have very good glucose markers so not speaking from personal experience but from what I’ve read, since you’re already on metformin, perhaps up the dose if feasible (you didn’t say how much you take). Perhaps add acarbose to the mix. Definitely get akkermansia for a few months (ideally from pendulum since they seem to make the biggest deal about their probiotics being alive and viable) and support their maintenance and perpetuation in your GI with a careful fiber blend: metformin they already supposedly love, but also green tea polyphenols, rhubarb, and fructooligosaccarides. More fiber and greater fiber variety should be great for glucose control anyway.

Add dihydroberberine to the mix (much more bio available than barberine so you need lower dose).

Perhaps make those vinegar hacks part of your meal rituals.

I think any subset of these should help. And not everyone gets higher glucose from rapa anyway — I haven’t. Just be careful re: Berberine as it seems to increase metformin’s effective dosage so watch out how to best introduce it and at what dose. Then just test and test to see if you’ve hit a good spot.


I thought I saw in passing you post about an episode of your podcast re: periodically challenging the body and one of the challenges was blood sugar related. Did I dream that up? I lost the comment.

It’s possible. My thinking is that a metabolically healthy person is flexible in the ability to eat carbs and fats without problems. To maintain this ability I eat a mix of carbs and fats along with my proteins. I limit added fats because of the calorie load. And because I also want fiber and phytonutrients for my gut health (microbiome and SCFA for my gut tissues), I eat my carbs calorie budget in the form of whole (or ground up) plants. I aim for 30 different plants each week.

I avoid processed foods to avoid the additives, the addictive tendencies, and the ease of overeating.

During the holidays I eat what is put in front of me. I enjoy and regret it every time. I doubt it makes me more resilient.


As a type 1 diabetic on a keto diet, the only effect of rapamycin I have seen is lower blood sugars for several days after taking my dose every 2 weeks. So I don’t have a normal metabolism, but rapa doesn’t cause blood sugar problems for me.

By most, if not all accounts, any increases in fasting sugars ramp up slowly. If you are worried, just take a lower dose or take a break from rapa every 8-12 weeks or whenever you notice a blood sugar increase. If you don’t have a blood glucose meter, get one and measure your fasting sugars every once in a while. If you are around the normal fasting 75-95 mg/dL range, you’re fine.


I think part of the progressive increasing glucose effect we see with rapa is similar to what is seen in intial keto. There is a reducition in pancreatic beta cell mass from its previous hypertrophic induced increased mass state created from varying degrees of metabolic dysfunction. Beta cell hypertrophy is one of the first inital changes in insulin resiatance/metabolic dysfunction and can be seen in the increase in peak and then fasted insulin levels. Inhibit mtorc1 and it is in simplistic terms rescuing the beta cells from the constant mtorc1 growth activity.

Metaformin on the other hand at tbe pancreas protects beta cell function but does not effect or signifucantly effect the hypertrophic ability of the beta cells. Its effect is mostly hepatic also gut microbe modulation.

Combining the the two compounds (rapamycin & metaformin) nets you the benefits of both which complement each other. Decreased glucose from inhibiting gluconeogenesus. Favorable chamges in gut microbe balance. Increasing hepatic insulin sensitivity. Decreasing or a return to a nominal (healthy) beta cell mass. Protecting current beta cell function. Repairing beta cell function. AMPK activation & inhibiting mtorc1. Decrease in hepatic and pancreatic inflammation which positively & dramatically effects entire body. Brain, kidneys, centire dardiovascular system, skeletal etc.


Yes - there are many benefits to metformin. But people should also be aware of the impact on muscle recovery after exercise. See this thread: Rapamycin + Metformin