Have been trying to figure out how to achieve the optimum balance for me personally. It seems that many of the readers on this forum are more “anabolic,” and are taking rapamycin. I myself am more catabolic: a thin, small-boned, osteoporotic, low-muscled older female. Searching for the right strategy to avoid sarcopenia, and hopefully build muscle. Recently did a scan that confirmed my suspicions: very low fat but very low metabolic rate, likely because there is so little muscle. (It goes without saying that I need to do more and heavier resistance training).
So, I take metformin (also a little Berberine) to keep glucose at an acceptable level (Repatha drives it up and it was slightly high even before starting that). But metformin stunts muscle hypertrophy, and that scan heightened my alarm about the metformin. What to do? Considering microdosing a GLP1 but my experience with even the tiniest starter dose of Rybelsus was a disaster – lost weight fast (not what I needed to do) and developed gallstones.
So, just found research showing that taking leucine plus sildenafil together with metformin can at least partially prevent the metformin from stunting the growth of muscle. The protocol for this combination is "
0200". It was written up in several publications such as the Journal of Obesity. As I do not eat red meat I was already taking a small intermittent dose of leucine plus tadalafil. Will increase the leucine. This seems like a low risk, low cost strategy to at least partially blunt the negative effect of the metformin.
Would appreciate having opinions and pointers on this.
Seconding @cl-user wrt. imeglimin. As I recall, you have extremely low insulin levels with that elevated glucose. It is possible - just a hypothesis - that you have some beta cell defect obstructing insulin production/release. In this context, imeglimin is especially helpful as it fixes beta cell defects along a certain pathway (go to the thread for more details). Given your biomarkers you seem like a very good candidate for imeglimin based on its MOA. Not a doctor, not medical advice, YMMV.
The combination of metformin and leucine also fails to improve muscle volume. Leucine itself is a potent mTOR activator that every fitness enthusiast takes for muscle growth; however, building muscle is difficult even without taking metformin. Hypertrophy requires high levels of testosterone. If your goal is to build muscle, I suggest you ditch the metformin; otherwise, no matter how much resistance training you do, it will be a wasted effort.
While low body fat helps extend lifespan for young people, the opposite is true for the elderly. This explains why Dr. Alan Green, who prescribed Rapamycin for anti-aging to over 1,500 people, didn’t even live as long as the average American life expectancy.
There is also the Editor-in-Chief of the journal Aging—Mikhail Blagosklonny—who was the first to publish on Rapamycin for anti-aging and one of the earliest to take it himself; yet he reportedly only lived into his 70s. Even intermittent inhibition of mTOR can be fatal for the elderly, let alone combining it with Metformin. Even David Sinclair avoids taking Metformin on workout days, so imagine the risk for seniors. The elderly actually need body fat and muscle mass to protect themselves.
As for Imeglimin, there is absolutely no reason to take it. In discussion threads regarding Imeglimin, no one can produce a single peer-reviewed paper related to anti-aging; it’s all just AI-generated nonsense. There is no point in looking into it further. Without a shred of actual anti-aging research, people are simply fantasizing about it being a replacement for Metformin.