What does metformin do exactly ?

[fredmac82]

Metformin increases insulin sensitivity which is a good thing. If your taking anabolics and GH along with Metformin which most of us probably are then there isn't any real downside to taking Metformin. There is a reason Metformin is used in the world of bodybuilding and many bodybuilders use it.

 

[Type-IIx]

This bit is new to me. Does metformin have any other deleterious effects on the outcome of those modes of training? As in, does it blunt any of the other adaptations one would expect to see from endurance training?

Not insofar as I am aware, but I am not certain whether Met has been studied for effects on the entirety of ET adaptations (cardiac output, stroke volume, O₂ uptake, etc.) - I doubt both that it's been studied and that it'd blunt cardiovascular adaptations and the like; but I also doubted that it'd meaningfully affect strength, hypertrophy, or endurance training adaptations at all, and I was wrong.

 

[Type-IIx]

So based on this, metformin sounds like a hindrance to body composition?

Sorry bro, ask a simple question, get a complex answer:

It's always more complicated with drugs like biguanides that affect so many systems and tissues, than to permit straightforwardly a conclusion like "good" or "bad," or any synonym thereof, with respect to body composition (itself a function of multiple factors that affect fat mass and skeletal muscle accrual).

The use of Metformin requires considering the tradeoffs to its use. This requires knowing A) what the risks are, B) what the rewards are, C) the rough probabilities thereof, and D) balancing these with respect to your own individual risk tolerance.

While generally Met's use is irrational for those not using rhGH & AAS (combined) that seek hypertrophy and/or strength because of the aforementioned effects (i.e., blunted training adaptations) and because Metformin reduces testosterone (free & total) & increases SHBG in healthy men, its use is absolutely rational for those that are experiencing hyperglycemia and insulin resistance due to rhGH use.

RhGH in my view generally necessitates some additional drug use at efficacious dosing for management of blood glucose, falling on a continuum, where biguanides/GDAs (e.g., Met, berberine) < incretins (e.g., GLP-1 & GIP agonists) [while these may be roughly equivalent to SGLT-2 & DPP-4 inhibitors, some sulfonylureas and the like, I believe that GLP-1 & GIP agonists are preferable] < IGF-I & its analogues (e.g., LR3 IGF-I) < slin. That is, with some dose-dependency, you move along the continuum, and with a shift rightward on the dose curve, you also shift from simple glucose management to increasing IGF-I bioavailability & total-body growth.

While AAS do not in any way prevent Met's harmful direct effects on hypertrophy (because they don't block Met's AMPK activation) and it is unknown whether AAS affect Met's preferentially increasing type I-associated satellite cells (they might do so, perhaps even compound-dependently, as there is evidence that testosterone simply increases size of both type I & II fibers equipotently, there are some [unfortunately low quality] datapoints that suggest that different AAS preferentially grow type II fibers), AAS just potently stimulate hypertrophy (by different pathways) and for this reason, a person that uses Met while using AAS may achieve a remarkable physique, albeit to some extent less impressive than it otherwise would be.

 

[hawkmoon]

Anecdotal, so take it as you will, but for me metformin has:

Halved triglycerides
Lowered LDL
Increased pumps and fullness
Made it MUCH easier to stay lean

 

[claymore]

How no one has mentioned uncontrollably DIARRHEA is beyond me lol

 

[hawkmoon]

How no one has mentioned uncontrollably DIARRHEA is beyond me lol

I keep hearing this, but fortunately never experienced it.

 

[lifter]

How no one has mentioned uncontrollably DIARRHEA is beyond me lol

Extended Release is better than regular release for cha cha cha

 

[ChisledFat]

How no one has mentioned uncontrollably DIARRHEA is beyond me lol

For me, this side effect lasted under 2 weeks. It's a good idea to start at a low dose and titrate upward if planning to use metformin for the long haul. Metformin has also had a definite positive impact on my body composition.

 

[whacked]

I keep hearing this, but fortunately never experienced it.

Same

All. Don’t forget to keep an due on B12 levels while using MF or just add it.
*Opt for methylcobalamin vs cyanocobalamin

 

[qbkilla]

Sorry bro, ask a simple question, get a complex answer:

It's always more complicated with drugs like biguanides that affect so many systems and tissues, than to permit straightforwardly a conclusion like "good" or "bad," or any synonym thereof, with respect to body composition (itself a function of multiple factors that affect fat mass and skeletal muscle accrual).

The use of Metformin requires considering the tradeoffs to its use. This requires knowing A) what the risks are, B) what the rewards are, C) the rough probabilities thereof, and D) balancing these with respect to your own individual risk tolerance.

While generally Met's use is irrational for those not using rhGH & AAS (combined) that seek hypertrophy and/or strength because of the aforementioned effects (i.e., blunted training adaptations) and because Metformin reduces testosterone (free & total) & increases SHBG in healthy men, its use is absolutely rational for those that are experiencing hyperglycemia and insulin resistance due to rhGH use.

RhGH in my view generally necessitates some additional drug use at efficacious dosing for management of blood glucose, falling on a continuum, where biguanides/GDAs (e.g., Met, berberine) < incretins (e.g., GLP-1 & GIP agonists) [while these may be roughly equivalent to SGLT-2 & DPP-4 inhibitors, some sulfonylureas and the like, I believe that GLP-1 & GIP agonists are preferable] < IGF-I & its analogues (e.g., LR3 IGF-I) < slin. That is, with some dose-dependency, you move along the continuum, and with a shift rightward on the dose curve, you also shift from simple glucose management to increasing IGF-I bioavailability & total-body growth.

While AAS do not in any way prevent Met's harmful direct effects on hypertrophy (because they don't block Met's AMPK activation) and it is unknown whether AAS affect Met's preferentially increasing type I-associated satellite cells (they might do so, perhaps even compound-dependently, as there is evidence that testosterone simply increases size of both type I & II fibers equipotently, there are some [unfortunately low quality] datapoints that suggest that different AAS preferentially grow type II fibers), AAS just potently stimulate hypertrophy (by different pathways) and for this reason, a person that uses Met while using AAS may achieve a remarkable physique, albeit to some extent less impressive than it otherwise would be.

Good stuff as always.

How do we determine insulin sensitivity? When I began gh I started testing blood sugar in the am. It was always over 100. At home meter. But at doctor it was always perfect. All tests fasted. I began taking metformin it had no affect on these numbers. I'm thinking I have insulin resistance going on now.

I then got my a1c tested and find out it's actually low out of range. 4.3 then 4.7. this would indicate the opposite of what my hand glucose monitor says, that I'm very insulin sensitive, correct?

Is there a specific test that determines if we have good insulin sensitivity?

 

[fredmac82]

Metformin is a biguanide, a class of drugs that aid in glucose disposal. Metformin decreases blood glucose levels by reduced gluconeogenesis (liver), decreased glucose absorption (intestines), and increasing insulin sensitivity (liver) by increasing glucose uptake and utilization.

While it seems a popular idea that Met increases skeletal muscle insulin sensitivity (which would be great for muscle anabolism), the primary site of its insulin sensitizing effects is the liver. Its actions on skeletal muscle is actually quite negative: it inhibits mTOR complex 1 (protein synthesis, translation) thereby reducing hypertrophy; it blocks the preferential shift from type I to type IIA fibers (resulting in a tendency towards reduced strength gains); and blocks the endurance training (LISS, HIIT, cardio) enhancement of insulin sensitivity. When Metformin alone is compared to a progressive resistance training program alone in older sedentary people, its effects (on blood glucose levels & absorption, insulin sensitivity) are indistinguishable from the resistance training program alone; and Metformin + progressive resistance training does worse than either Metformin with no training and/or resistance training alone.

Insulin (exogenous) promotes the uptake & utilization of glucose from the blood into skeletal muscle, repleting glycogen, enhancing insulin sensitivity in skeletal muscle. Rather than blunting fat synthesis & promoting fat oxidation like Metformin (another of Met's effects), it does the opposite potently, and dramatically increases VLDL synthesis in the liver (increasing the most dangerous particles for cardiovascular risks). Over time at high doses, it worsens insulin sensitivity by diminished autophosphorylation of the IR & its downstream elements, thereby reducing this skeletal muscle uptake of glucose and logically (though it has not been demonstrated insofar as I am aware) the muscle protein anabolic effects. See Insulin’s effects and mechanisms in promoting skeletal muscle hypertrophy, November 17, 2022, Type-IIx MesoRx Article

While the two drugs (Met & slin) may be used in diabetic patients, it requires dose reductions, and this is further complicated by AAS (that increase insulin sensitivity in skeletal muscle). Since slin so potently overwhelms the effects of Met and they act oppositely in some key ways, this should be considered before combining the two. A potential very high severity outcome is hypoglycemic shock, coma, and death.

I have heard Metiform inhibits mTOR complex 1 (protein synthesis, translation) thereby reducing hypertrophy. But if your taking anabolics this would counteract the inhibition of mTOR and it would not reduce hypertrophy in a person on gear. If you're on gear and taking Metiform you wouldn't have to worry about mTOR being reduced. I think this study was done on old sedentary people taking Metiform and not enhanced folks like ourselves.

 

[Scuncknuts]

I use 2000 mg every day to lower blood sugar and increase insulin sensitivity. It also lowers IGF1 which promotes longevity.

This is really dumb

 

[Scuncknuts]

Why don't talk just eat healthier and insulin sensitivity won't be a problem. Sometimes less is more

 

[Muay Thai]

Take the bad into consideration, but also take the good. I've been taking MET for years and I have only noted a slight drop in B12 (and related iron deficiency) on MET and BERB. Metformin not only reduces inflammation reducing cardiac events but is cardio protective, reduces kidney strain, and has neuroprotective effects that reduce cognitive decline, etc. It also is beneficial in regards to insulin resistance due to the traditional BBer high caloric intake - taking stress off beta cells and improved pancreatic function. It's important that we not look at MET as a PED.

I'm going to copy part of this well-referenced article here.
I highly recommend reading the full article:

Link: "Metformin: A Novel Weapon Against Inflammation"

"Beyond its consolidated role in T2D management, the pleiotropic actions of metformin have been extensively documented. Metformin can treat cardiovascular diseases by mechanisms distinct from its metabolic activities (Soraya et al., 2014; Liu et al., 2017; Dziubak et al., 2018). Metformin exerts nephroprotective effects in diabetic patients (Kawanami et al., 2020) and interferes with key immunopathological molecules involved in tumor progression (Ma et al., 2020). These findings, together with one particular breakthrough in metformin-induced longevity in microbes and mice (Cabreiro et al., 2013; Martin-Montalvo et al., 2013; Chen et al., 2017), provide the possibility of boosting its therapeutic potential in treating aging and age-related diseases (Storelli et al., 2013). Of note, emerging in vitro and in vivo evidence suggests that metformin can exert potent inflammation-inhibitory effects, irrespective of its capability of glucose control (Saisho, 2015; Bharath et al., 2020). Most recently, it is of great interest to find that metformin is able to dampen cytokine storms in patients who are infected with coronavirus disease 2019 (COVID-19). The use of metformin is significantly associated with reduced circulating levels of inflammatory markers (Cheng et al., 2020) and decreased in-hospital mortality (Hariyanto and Kurniawan, 2020; Kow and Hasan, 2020; Luo et al., 2020). It has become widely accepted that inflammation is a driving force behind various chronic diseases, including heart failure, atherosclerosis, diabetes, obesity, neurodegenerative disease, cancer, etc. The reduction in lifetime exposure to inflammation has contributed to the historical decline in old-age mortality (Finch and Crimmins, 2004; Couzin-Frankel, 2010)."

excellent rebuttal, thank you to all contributors of this thread. I am teeter-tottering whether to continue MET or not, these benefits aforementioned are applicable to me, and im wondering if we can offset the counter-productive hypertrophy effects of the met with PEDS safely

 

[slesh]

How no one has mentioned uncontrollably DIARRHEA is beyond me lol

I hear this a lot as well. Without getting too gross - I don’t get diareah but I would say it’s def a “looser” stool than before I started taking it. But other than that this has been a miracle drug for me in terms of insulin sensitivity. I just pray I don’t eventually build a tolerance and become resistant to it.

 

[slesh]

Why don't talk just eat healthier and insulin sensitivity won't be a problem. Sometimes less is more

We don’t take it because we are like the other lazy fat Americans who now take Ozempic as a fat loss drug. Majority of us are using it because our GH use fucks with insulin sensitivity. Literally nothing you can do diet or training wise to combat that. Most on here know how clean I eat and do fasted cardio 365 days a year. When I started high dose GH my fasted blood glucose went from 85 to 115.

 

[Fat]

Why don't talk just eat healthier and insulin sensitivity won't be a problem. Sometimes less is more

I am genetically disposed to diabetes, so I offset it with medication.

 

[OuchThatHurts]

excellent rebuttal, thank you to all contributors of this thread. I am teeter-tottering whether to continue MET or not, these benefits aforementioned are applicable to me, and im wondering if we can offset the counter-productive hypertrophy effects of the met with PEDS safely

I like to think of it more as just additional data to consider. It's a slam dunk "yes" for me because I'm not looking to get any bigger now that I'm over 50. I still train intensely and get plenty of rigorous exercise but longevity and avoiding a pre-diabetic state are my primary goals now. Because I do up the calories no doubt, especially in winter. And I love food.

Would I have taken it in my 20's and 30's? I doubt it. Longevity was of no concern to me then. I never thought I'd even see 50 with the way I behaved. But here I am. Everything Type-IIx wrote is likely true. He's darn good with research without a doubt.

But with MET and BERB, as with any drug or supplement, we weigh the strengths and weaknesses and decide if it's right for us. What conclusion we come to will be what it will be. Some pretty big dudes out there taking MET, though.

Can PEDs and B12/Fe supplementation offset the AMP-activated protein kinase, VLDL, and B12 effects? I don't know. Maybe we'll never know. Opinions are mixed as always. Studies are as well. All I can say is that I tolerate very well and will probably take it and rhGH for the rest of my days (or at least until I'm ready to leave it all behind). But I'm not there yet. Not at all.

 

[cage99]

This is really dumb

Why don't talk just eat healthier and insulin sensitivity won't be a problem. Sometimes less is more

You do realize the majority of folks here that are using Metformin are using it to combat GH induced insulin resistance? Others due to being diabetic! Diet and exercise wont do shit for that.

Cage

Cage

 

[Cerberus777]

excellent rebuttal, thank you to all contributors of this thread. I am teeter-tottering whether to continue MET or not, these benefits aforementioned are applicable to me, and im wondering if we can offset the counter-productive hypertrophy effects of the met with PEDS safely

"Trained testers" don't lift or workout like we do. MET hasn't been tested on endurance athletes either, i know guys on 150mg test and EPO who take MET. Hard work changes MTOR more than MET does. Add an anabolic and you get even better results. IMHO the health benefits(reduces chronic inflammation) only add to the ability to build a better body.