hGH + Metformin: A Good Thing (Metformin does not lower, but rather increases IGF-1)

[lukiss96]

It blunts some training adaptations and has other considerations, it'd take an article to really hash it all out. I view its use as generally favorable for bodybuilders on rhGH (and AAS) and less so for other use cases.

But what if metformin is used with testosterone only? Do we need higher dose or something more moderate like 200-300mg would be enough? Also is long term use sustainable? What would be some advantages and disadvantages using metformin in this case?

Sorry if that's a lot of questions, but just in general very interesting what's your opinion if no hgh is used.

 

[Type-IIx]

But what if metformin is used with testosterone only? Do we need higher dose or something more moderate like 200-300mg would be enough? Also is long term use sustainable? What would be some advantages and disadvantages using metformin in this case?

Sorry if that's a lot of questions, but just in general very interesting what's your opinion if no hgh is used.

I must not have seen this post, I apologize for not answering sooner. Instead of answering inline all your questions, I'll give you a more general answer that should answer these questions without getting into dosages:

Met & T without rhGH is really something to think hard about whether you should do, and presupposing that you must add drugs without being able to defend your reasoning is folly.

The benefits to Met & T without rhGH are few, but include reduced BPH risk & highly speculatively, potential amelioration of AAS-induced cardiac changes – but do not rely on this to reverse or block these changes on a blast, only for some minor benefit while on TRT.

The rough contours of the process you might follow to decide on whether to use Met while on T/TRT is as folows:

First, how severe is your hyperglycemia on TRT/T only (considering that TRT/T is insulin sensitizing)? Is your HbA1C > 5.7% and fasting blood glucose consistently > 100 mg/dL (5.6 mmol/L), i.e., early prediabetic while on TRT/T? If so, and only if so, then you may begin to think about Met.

But compare/contrast Met vs. the GLP-1 & GIP agonists that do not blunt training (resistance/weight & aerobic endurance/cardio) adaptations and offer myriad ancillary benefits that include enhanced body composition. These likely will serve you better and serve as an outright replacement (i.e., frank superiority) for Met.

The subsequent steps of this process would include a risk/reward (tradeoff) analysis or balancing of decisionmaking factors, that you cannot really do without knowing these factors.

 

[bigman1234]

Wow. Some seriously awesome high quality discussions happening here. First time posting to the forums. Cheers everyone and thanks very much for some great reading and knowledge

 

[29trt]

I must not have seen this post, I apologize for not answering sooner. Instead of answering inline all your questions, I'll give you a more general answer that should answer these questions without getting into dosages:

Met & T without rhGH is really something to think hard about whether you should do, and presupposing that you must add drugs without being able to defend your reasoning is folly.

The benefits to Met & T without rhGH are few, but include reduced BPH risk & highly speculatively, potential amelioration of AAS-induced cardiac changes – but do not rely on this to reverse or block these changes on a blast, only for some minor benefit while on TRT.

The rough contours of the process you might follow to decide on whether to use Met while on T/TRT is as folows:

First, how severe is your hyperglycemia on TRT/T only (considering that TRT/T is insulin sensitizing)? Is your HbA1C > 5.7% and fasting blood glucose consistently > 100 mg/dL (5.6 mmol/L), i.e., early prediabetic while on TRT/T? If so, and only if so, then you may begin to think about Met.

But compare/contrast Met vs. the GLP-1 & GIP agonists that do not blunt training (resistance/weight & aerobic endurance/cardio) adaptations and offer myriad ancillary benefits that include enhanced body composition. These likely will serve you better and serve as an outright replacement (i.e., frank superiority) for Met.

The subsequent steps of this process would include a risk/reward (tradeoff) analysis or balancing of decisionmaking factors, that you cannot really do without knowing these factors.

Interesting that you say TRT is insulin sensitizing, I guess you mean in the context of going from hypo-gonadal to TRT ?
There seems to be a bell curve for this effect or at least the studies that I looked at seem to point in that direction as in androgens cause hyper-insulinemia that leads to insulin resistance over time but lack of androgens also leads to high blood glucose perhaps because of reduced nutrient partitioning ??

 

[Type-IIx]

Interesting that you say TRT is insulin sensitizing, I guess you mean in the context of going from hypo-gonadal to TRT ?
There seems to be a bell curve for this effect or at least the studies that I looked at seem to point in that direction as in androgens cause hyper-insulinemia that leads to insulin resistance over time but lack of androgens also leads to high blood glucose perhaps because of reduced nutrient partitioning ??

Going from hypogonadal to TRT evokes very clear reversal of insulin resistance and other contributors to the metabolic syndrome, yes.

AAS cause hyperinsulinemia? That's news to me. Endogenous hyperandrogenism (i.e., adrenal androgen excess; e.g., PCOS) in women is associated with metabolic syndrome & hyperinsulinemia (perhaps through regulation of the Ins gene in the pancreatic islet cells).

Hypogonadism in men contributes to insulin resistance, obesity & the metabolic syndrome because the AR regulates glucose and lipid metabolism via nuclear transcription factors (PPARγ, LXRα and FoxO1), adipocyte differentiation (committment of pluripotent preadipocytes, and so fat cell #), hypothalamic leptin sensitivity, mitochondrial function, inflammation, etc.

 

[29trt]

Going from hypogonadal to TRT evokes very clear reversal of insulin resistance and other contributors to the metabolic syndrome, yes.

AAS cause hyperinsulinemia? That's news to me. Endogenous hyperandrogenism (i.e., adrenal androgen excess; e.g., PCOS) in women is associated with metabolic syndrome & hyperinsulinemia (perhaps through regulation of the Ins gene in the pancreatic islet cells).

Hypogonadism in men contributes to insulin resistance, obesity & the metabolic syndrome because the AR regulates glucose and lipid metabolism via nuclear transcription factors (PPARγ, LXRα and FoxO1), adipocyte differentiation (committment of pluripotent preadipocytes, and so fat cell #), hypothalamic leptin sensitivity, mitochondrial function, inflammation, etc.

Hmm I could have sworn I read a study about AAs inducing insulin secretion in men but the only studies I have saved indicating hyperinsulinemia involved PCOS women and a few rat studies...

I read about all this years ago when I started TRT and I noticed my blood sugar going up 10 points after a year ,but I also gained 26lbs in that time but kept the same body composition (about 13-15% BF) so I was eating like a MMF ,TRT increased my appetite especially my sweet tooth ... so maybe that skewed my memory about the studies...

 

[Type-IIx]

Hmm I could have sworn I read a study about AAs inducing insulin secretion in men but the only studies I have saved indicating hyperinsulinemia involved PCOS women and a few rat studies...

I read about all this years ago when I started TRT and I noticed my blood sugar going up 10 points after a year ,but I also gained 26lbs in that time but kept the same body composition (about 13-15% BF) so I was eating like a MMF ,TRT increased my appetite especially my sweet tooth ... so maybe that skewed my memory about the studies...

Makes sense.

 

[Jaxino]

When I first started aas, 7 years ago or so, and I was hypogonadal (diagnosed), also my sweet tooth increased dramatically.
Took me more than a year to finally get back into a normal dieting regimen.
At that time I didn't know anything about Metformin, it really could help me a lot....

 

[29trt]

When I first started aas, 7 years ago or so, and I was hypogonadal (diagnosed), also my sweet tooth increased dramatically.
Took me more than a year to finally get back into a normal dieting regimen.
At that time I didn't know anything about Metformin, it really could help me a lot....

Did you notice your sweet tooth correlates with your E2 level, as in higher the E2 more cravings?
I've seen reported a few times but could not find studies...
And I believe this mechanism works in some and not in others as for some EQ raises appetite and others(like me) it does not affect it... same as it seems to lower E2 only in some guys... very weird and diverse is our reaction to AAS )

 

[HB_22]

Well, I think that the use of agents to ameliorate the hyperglycemic effects of rhGH falls on a continuum, that looks like: biguanides/GDAs (Met, BBR, etc.) < incretins (e.g., GLP-1 & GIP agonists) < rhIGF-I & LR3-IGF-I < insulin, but the rationale for use of slin is not merely glucose disposal.

Do you have any experience or any knowledge about the use of let's say low dose glimepiride (3rd generation sulfonylureas) (perhaps 0.25mg daily, or 0.5mg) instead of using Metformin or GLP-1 agonists? Let's say I don't feel well on GLP-1 agonists and I would like to not take Metformin for specific reasons, what other drugs do you think could be of use to prevent insulin resistance from rHGH use?

 

[Type-IIx]

Do you have any experience or any knowledge about the use of let's say low dose glimepiride (3rd generation sulfonylureas) (perhaps 0.25mg daily, or 0.5mg) instead of using Metformin or GLP-1 agonists? Let's say I don't feel well on GLP-1 agonists and I would like to not take Metformin for specific reasons, what other drugs do you think could be of use to prevent insulin resistance from rHGH use?

Sulfonylureas are disfavored because of their effects on skeletal muscle. This class of drugs' mechanism of action is blockade of the ATP-sensitive K⁺ channel. While this results in insulin secretion in the pancreatic islet β cell, in skeletal muscle cells this is associated with atrophy (muscle loss).

Classes of drugs that can serve to ameliorate rhGH hyperglycemia include incretins (e.g., GIP & GLP-1 agonists, SGLT-2 inhibitors, DPP-4 inhibitors), and insulin secretagogues and mimetics (e.g., sulfonylureas).

 

[HB_22]

Sulfonylureas are disfavored because of their effects on skeletal muscle. This class of drugs' mechanism of action is blockade of the ATP-sensitive K⁺ channel. While this results in insulin secretion in the pancreatic islet β cell, in skeletal muscle cells this is associated with atrophy (muscle loss).

Classes of drugs that can serve to ameliorate rhGH hyperglycemia include incretins (e.g., GIP & GLP-1 agonists, SGLT-2 inhibitors, DPP-4 inhibitors), and insulin secretagogues and mimetics (e.g., sulfonylureas).

Thanks for you opinion. I came across this muscle athrophy claim too, but there is conflicting data on it as far as I can tell from my own research. Im wondering if it's actually the same minimal risk that is associated with Metformin too, and is most likely dose dependend.


What I mean is this:

One “in vitro” study of sulfonylureas and glinide-induced atrophy in skeletal muscles elucidated their efficacy in reducing the protein content in the flexor digitorum brevis (FDB) muscle in mice. The study revealed that the relative efficacy of diabetes medications in reducing the protein content in the FDB muscle after 24 hours of incubation time is as follows: repaglinide ≥ glibenclamide > glimepiride > tolbutamide > nateglinide [30]. A search of atrophy-related signaling in the Food and Drug Administration Adverse Event Reporting System (FDA-AERS) showed that muscle atrophy occurred in 0.27% of human subjects who had used glibenclamide, whereas no atrophy was reported in subjects who had used sulfonylureas or glinides [30].

Or this one:

In a cross-sectional study, Rizzo et al. observed that sarcopenic parameters (SMM, SMI, muscle strength, and gait speed) were significantly worse in patients with T2MD taking sulfonylureas compared with DPP-4i [94], while in a clinical trial no changes in SMM were reported in patients with T2DM assigned to sulfonylureas.

The Impact of Glucose-Lowering Drugs on Sarcopenia in Type 2 Diabetes: Current Evidence and Underlying Mechanisms

The age-related decrease in skeletal muscle mass together with the loss of muscle power and function is defined sarcopenia. Mounting evidence suggests that the prevalence of sarcopenia is higher in patients with type 2 diabetes mellitus (T2DM), and different mechanisms may be responsible for...

www.mdpi.com

 

[Type-IIx]

Thanks for you opinion. I came across this muscle athrophy claim too, but there is conflicting data on it as far as I can tell from my own research. Im wondering if it's actually the same minimal risk that is associated with Metformin too, and is most likely dose dependend.


What I mean is this:


Or this one:

The Impact of Glucose-Lowering Drugs on Sarcopenia in Type 2 Diabetes: Current Evidence and Underlying Mechanisms

The age-related decrease in skeletal muscle mass together with the loss of muscle power and function is defined sarcopenia. Mounting evidence suggests that the prevalence of sarcopenia is higher in patients with type 2 diabetes mellitus (T2DM), and different mechanisms may be responsible for...

www.mdpi.com

What about my post was the domain of opinion, that sulfonylureas are disfavored because of muscle atrophy risks? I see a lot of use of terms like "claims" and "opinions" in response to a post that wasn't really a persuasive writing piece.

Before we even waste time here, can you even make an argument for a use case for sulfonylureas in bodybuilding given a muscle atrophy risk of any magnitude?

Assuming, for the sake of argument, that the risks posed by biguanides (e.g., Metformin) are comparable in substance & severity to sulfonylureas (e.g., gliperizide), do we wish to invite widespread use of sulfonylureas where not yet established, quite unlike Metformin that has been established and readily available for decades, before these risks were known? To analogize, this is a problem of opening the floodgates vs. putting a poured liquid back into its bottle.

Or do we dissuade their adoption into widespread use because of the plethora of other superior agents that, not only do not pose muscle atrophy and reduced muscle strength as risks, but actually the opposite, enhance muscle hypertrophy & function (e.g., incretins, IGFs, insulin)?

 

[HB_22]

Before we even waste time here, can you even make an argument for a use case for sulfonylureas in bodybuilding given a muscle atrophy risk of any magnitude?

You are right about not wasting any more time. I can't find any evidence, medical paper or study that sulfonylureas and especially glimepiride is known to cause muscle athrophy. As I said the data on that claim is conflicting, there's evidence supporting both that it's muscle wasting and other studies that didn’t find anything pointing into this direction. As long as this is the current state of where research is stuck at it is what I would call a claim.

Anyways, have a good day.

 

[Type-IIx]

You are right about not wasting any more time. I can't find any evidence, medical paper or study that sulfonylureas and especially glimepiride is known to cause muscle athrophy. As I said the data on that claim is conflicting, there's evidence supporting both that it's muscle wasting and other studies that didn’t find anything pointing into this direction. As long as this is the current state of where research is stuck at it is what I would call a claim.

Anyways, have a good day.

OK rereading what I wrote, maybe what I said was a little tone deaf, because you weren't asking about promoting sulfonylureas, only saying that you basically doubted that the evidence of their promoting muscle atrophy would be substantiated.

The evidence that you cannot find is cited by your own post above. Iif you care to do so you can seek out the reference to the cross-sectional data for human evidence of muscle atrophy, but not the clinical trial that did not support it. There's this mechanistic paper, a review with some in vitro evidence & that suggests glimepiride is fairly agnostic in its effects on muscle, Mele A, Calzolaro S, Cannone G, Cetrone M, Conte D, Tricarico D. Database search of spontaneous reports and pharmacological investigations on the sulfonylureas and glinides-induced atrophy in skeletal muscle. Pharmacol Res Perspect. 2014 Feb;2(1):e00028. doi: 10.1002/prp2.28. Epub 2014 Mar 3. PMID: 25505577; PMCID: PMC4186404. I'm sure there is a lot more evidence, but I am content to just not use or promote something that is basically an insulin secretagogue with potentially detrimental effects that has already fallen out of use in practice because of the availability of better alternatives, that all sort of came out as products of R&D for treating insulin resistance, metabolic syndrome, prediabetes, etc. around the same time, more or less.

 

[HB_22]

OK rereading what I wrote, maybe what I said was a little tone deaf, because you weren't asking about promoting sulfonylureas, only saying that you basically doubted that the evidence of their promoting muscle atrophy would be substantiated.

The evidence that you cannot find is cited by your own post above. Iif you care to do so you can seek out the reference to the cross-sectional data for human evidence of muscle atrophy, but not the clinical trial that did not support it. There's this mechanistic paper, a review with some in vitro evidence & that suggests glimepiride is fairly agnostic in its effects on muscle, Mele A, Calzolaro S, Cannone G, Cetrone M, Conte D, Tricarico D. Database search of spontaneous reports and pharmacological investigations on the sulfonylureas and glinides-induced atrophy in skeletal muscle. Pharmacol Res Perspect. 2014 Feb;2(1):e00028. doi: 10.1002/prp2.28. Epub 2014 Mar 3. PMID: 25505577; PMCID: PMC4186404. I'm sure there is a lot more evidence, but I am content to just not use or promote something that is basically an insulin secretagogue with potentially detrimental effects that has already fallen out of use in practice because of the availability of better alternatives, that all sort of came out as products of R&D for treating insulin resistance, metabolic syndrome, prediabetes, etc. around the same time, more or less.

That's something I can work with, thank you
I apologize if I came off inpolite.

 

[Sampei]

@Type-IIx what's your opinion in taking Metformin 2g a day and semaglutide during hgh assumption (on TRT)? Too much? Just go for semaglutide and drop the Metformin?

 

[Type-IIx]

@Type-IIx what's your opinion in taking Metformin 2g a day and semaglutide during hgh assumption (on TRT)? Too much? Just go for semaglutide and drop the Metformin?

Well, 2 g/d Met is fine without semaglutide (where the primary rationale is fiscal) on TRT & rhGH, depending on rhGH dose & nadir blood glucose readings.

I generally would never combine Met & semaglutide, just move from one to the other where appropriate as you move up the continuum, from biguanides to incretins to IGF-I and its analogues to insulin, and the rationale shifts from maintaining insulin sensitivity to increasing IGF-I bioavailability.

 

[Sampei]

Well, 2 g/d Met is fine without semaglutide (where the primary rationale is fiscal) on TRT & rhGH, depending on rhGH dose & nadir blood glucose readings.

I generally would never combine Met & semaglutide, just move from one to the other where appropriate as you move up the continuum, from biguanides to incretins to IGF-I and its analogues to insulin, and the rationale shifts from maintaining insulin sensitivity to increasing IGF-I bioavailability.

I don't plan to go into the territory of incretins or insulin or any other substances except HGH - sema - Metformin - TRT.

So I'll just cycle between semaglutide and Metformin, the thing I still don't understand (because of my ignorance and probably need to research it more) semaglutide hunger effect subsidize after a while but the insulin sensitivity effect stay the same right? So for example if with 1mg week I have a good BG (associated with my daily dosage of HGH) can I just keep 1mg week indefinitely? Should I still ramp up with time? Cycle on and off?

 

[Type-IIx]

I don't plan to go into the territory of incretins or insulin or any other substances except HGH - sema - Metformin - TRT.

So I'll just cycle between semaglutide and Metformin, the thing I still don't understand (because of my ignorance and probably need to research it more) semaglutide hunger effect subsidize after a while but the insulin sensitivity effect stay the same right? So for example if with 1mg week I have a good BG (associated with my daily dosage of HGH) can I just keep 1mg week indefinitely? Should I still ramp up with time? Cycle on and off?

Correct. Incretins (e.g., semaglutide) enhance insulin sensitivity by several mechanisms, one of which is a transient appetite/hunger blunting effect, indirectly reducing energy intakes, thereby promoting reduced fat stores & blood sugar/fatty acid elevations. Independent from that effect, are other effects, that converge on insulin sensitization (e.g., GLP-1 mediated- coupling of blood glucose & insulin secretion, decreased glucagon secretion, delayed gastric emptying, etc.) The benefits of incretins do not depend solely on appetite/hunger blunting.

Without getting into protocols and dosing, I'll just say that the basic instructional pamphlet included with the medication will guide you just fine.