Talk:Metformin

Pharmacokinetics

A quick question re elimination half-life and reference 39 Robert et al. The stated elimination half-life of 17.6 hours (in the last sentence of this section) is outside of the reported range of 18.5-31.5 hours.

...in red blood cells, with a much longer elimination half-life: 17.6 hours (18.5–31.5 hours in a single-dose study of non-diabetic people).[39]

I read the Robert et al journal article and didn't find the 17.6 hours in the text or tables. Did I overlook it or could this be a typo?

Lkbwiki (talk) 15:51, 9 August 2009 (UTC)

It was actually a source omission—17.6 hours is the nominal half-life reported in most of the literature, including the product information. The Robert et al. study, which reports a different range in non-diabetic subjects, was added as a counterpoint. Fvasconcellos (t·c) 16:01, 9 August 2009 (UTC)

Thanks for the quick response and page edit.Lkbwiki (talk) 16:20, 9 August 2009 (UTC)

Mechanism of lactic acidosis

I'm trying to figure out how Metformin causes lactic acidosis (if the information is out there in the medical literature. I don't want to do Original Research)

I'm going to post abstracts here to see if there's any relevant information. I only have an undergrad in biotech, so some of these abstracts are above my level.

these data indicate that biguanide-induced lactic acidosis can be attributed to acceleration of glycolysis in response to mitochondrial impairment. Indeed, the desired clinical outcome, viz., decreased blood glucose, could be due to increased glucose uptake and glycolytic flux in response to drug-induced mitochondrial dysfunction.

[1]

The development of AMPK(AMP-activated Kinase) activators which do not share metformin's modest risk of inducing lactic acidosis--apparently reflecting an inhibition of mitochondrial complex 1 that is not intrinsic to AMPK activity [2]

Metformin is, however, associated with a very low incidence of lactic acidosis because, differently from phenformin, it does not undergo liver metabolism and, as a consequence, there are no high-risk groups, displaying an impaired metabolic handling.

[http://www.ncbi.nlm.nih.gov/pubmed/7862618?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum ] phenformin is similar to metformin.

A mechanism of action for phenformin-associated lactic-acidosis, attributable to impaired mitochondrial function arising from inactivation of Ca2+-sensitive, NAD+-dependent mitochondrial dehydrogenases (e.g. 2-oxoglutarate dehydrogenase) due to alteration in mitochondrial calcium content, is proposed.

[http://www.ncbi.nlm.nih.gov/pubmed/2449214?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum ] When the concentration required to reduce the oxygen consumption to 75% of the control value (from 0.40 to 0.29 micromol/min/mg protein) was compared with the EC(50) value obtained in vivo, a clear correlation was observed among the three biguanides, suggesting that oxygen consumption in isolated rat hepatocytes can be used as an index of the incidence of lactic acidosis.

[3]

(from 2008) Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro.

As a class, the biguanides induce lactic acidosis, a hallmark of mitochondrial impairment...In toto, these data indicate that biguanide-induced lactic acidosis can be attributed to acceleration of glycolysis in response to mitochondrial impairment. Indeed, the desired clinical outcome, viz., decreased blood glucose, could be due to increased glucose uptake and glycolytic flux in response to drug-induced mitochondrial dysfunction.

[4]

There also seems to be some attempt to argue that Metformin doesn't cause lactic acidosis. It doesn't seem valid to me, but the view is being pushed (with the assertion that those cases of Metformin related lactic acidosis which are presented are incidental to metformin therapy)

CONCLUSIONS: While the term 'metformin-associated lactic acidosis' is commonly used to depict all situations of lactic acidosis in metformin therapy, true metformin-associated lactic acidosis, i.e. one which refers to metformin and concurrent pathologies as co-precipitating factors, was never observed in the studied reports. As there was no mortality due to metformin alone, it is important that physicians are familiar with the range of other risk factors that contribute to lactic acidosis in patients treated with metformin. [5]

Here, we report a 43-year-old woman with type 2 diabetes mellitus and chronic renal insufficiency who developed hypoglycemia, hypothermia, tachycardia and lactic acidosis after a suicide attempt with a metformin overdose. [http://www.ncbi.nlm.nih.gov/pubmed/19321413?ordinalpos=11&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum ] --Ryan Wise (talk) 16:35, 24 June 2009 (UTC)

Alzheimer Disease

The study relating Metformin with AD is being removed and there's no justification since that information came from a reliable source. If my text doesn't represent well the source rewrite it instead of deleting. If you don't agree with the importance the source gave to the matter balance it with equally sourced opinion.--Nutriveg (talk) 19:13, 10 March 2009 (UTC)

I tried to explain on your talk page why we don't normally include information from cellular models and animal studies in this kind of articles. Unless there is strong evidence of metformin causing dementia in man, I cannot imagine why the reader would find this relevant. It is certainly not the way WP:PHARM goes along with this kind of studies. I think it should be removed, not because the source is not reliable but because it overemphasises a curious phenomenon in a Petri dish that hasn't even been replicated. I shall await reactions from other contributors because removing your content again, but please be prepared to yield to consensus. JFW | T@lk 23:22, 10 March 2009 (UTC)

I really don't think this should be included yet—this is an early finding and hasn't even made it to animal studies yet. If other contributors feel this should stay, it should at least be reworded to something along the lines of "In vitro, metformin has been found to increase generation of amyloid beta." In retrospect, I'm not even sure the TSH suppression effect (the "Hormonal" section in the article) should be mentioned; it doesn't seem to have generated much interest in the literature, and there haven't been any solid studies. Fvasconcellos (t·c) 23:41, 10 March 2009 (UTC)

The source cited is from a legitimate, peer-reviewed source, and the research is relevant to the article. Though it is very early at this stage, and certainly more experiments are going to be done on this. I don't see any reason why it can't be included, but I've moved it to the very end of the 'adverse effects' section, and re-phrased it to indicate that it ***may*** have an effect, but the jury is still out on this one. Dr. Cash (talk) 15:20, 11 March 2009 (UTC)

I still think we should wait for further studies, or at least until this has been cited a few times! What do you think of the TSH suppression effect? I'd really like more input on this one—right now, I'm not sure it is worth mentioning either. It's been nearly three years since the report, surely it would have generated more research by now. Fvasconcellos (t·c) 15:39, 11 March 2009 (UTC)

You shouldn't assume the readers are all stupid, otherwise little content should be presented at wikipedia because other information should be blinded from those who might interpret it wrongly. The link to the in vitro wikipedia article is present, let the readers decide if it's worthy information or not. Many of them would understand that the precautionary principle applies. If you want to rewrite or balance, feel free to do so, but don't just remove information based on reliable source because you don't like it yourself. Nutriveg (talk) 17:28, 11 March 2009 (UTC)

Three years since the report? The PNAS article was published on 2/20/2009 -- 2-3 weeks ago. It's pretty new. But I do agree with your rephrasing it and combining the sections. That seems appropriate. Dr. Cash (talk) 18:33, 11 March 2009 (UTC)

Fv was referring to the TSH report from 2006, I believe. --ἀνυπόδητος (talk) 18:40, 11 March 2009 (UTC)

The sentence seems to claim (at least, to the unsuspecting reader) that accumulation of amyloid beta causes AD, or at least increases the risk to get AD. Since decrease of amyloid beta has no positive effects on AD (Holmes C; et al. (2008). "Long-term effects of Aβ42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial". The Lancet. 372 (9634): 216–233. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)), this might not be true at all. The relationship between AD and amyloid beta is less than clear at the moment, and it would need a much more careful formulation to reflect this.

Regarding the TSH suppression: I agree with Fv that this is simply not notable. There were no symptoms, no change in thyroid hormone levels, no known mechanism, so the information carried in this sentence is very nearly zero. --ἀνυπόδητος (talk) 18:41, 11 March 2009 (UTC)

I'm going to WP:BOLDly remove both items, as most commentators above seem to agree that it is too early to discuss AD and TSH. JFW | T@lk 19:24, 11 March 2009 (UTC)

Oh, and I insist on discussing all 5207 studies about metformin. In other words, a bit of balance is called for. JFW | T@lk 19:48, 11 March 2009 (UTC)

3 to 2, is just a basic majority, early is to consider there is a majority few minutes after that one opinion. Fell WP:BOLDly to include all the relevant information you find on those articles.--Nutriveg (talk) 20:11, 11 March 2009 (UTC)

Surely the lead section isn't the right place to mention the beta amyloid study? --ἀνυπόδητος (talk) 20:53, 11 March 2009 (UTC)

Probably not, but the other reference for it was removed, if you can find a better place for the information...--Nutriveg (talk) 20:58, 11 March 2009 (UTC)

Moving the information into another section doesn't get us anywhere. I put it back into the Adverse effects section where it belongs, if it does belong anywhere. Please, people, leave it there until there is some consensus. And don't introduce any more typos, if possible. Thank you --ἀνυπόδητος (talk) 21:36, 11 March 2009 (UTC)

This other study, on humans, confirms that Metformin (or glyburide, since the study doesn't differentiate) as monotherapy (without insulin) resulted in higher beta-amyloid plaques than combined therapy. However the study diverges saying that combined therapy is better than control.--Nutriveg (talk) 21:47, 11 March 2009 (UTC)

That's interesting. But it doesn't confirm (I like that word being used in medicine as much as I like the word "cure") that either drug is associated with an increase in plaque formation; it suggests that insulin has a protective effect. Might this be due to metformin increasing biogenesis of Aβ? Certainly—but we don't know yet. I am in no way disputing the merit of the Chen et al. study or its findings, I'm disputing the merit of mentioning these findings when they are so preliminary. For a drug that doesn't even have a fully elucidated mechanism of action yet, some of this research—like much of the research on the diabetes/AD connection—relies far too heavily on presumptions, possibilities, and borderline speculation for my taste. I'd rather see the article focusing on clearly defined facts of definite clinical importance and on "known unknowns" than on "unknown unknowns" :) Fvasconcellos (t·c) 22:08, 11 March 2009 (UTC)

I'm somewhat dismayed that Nutriveg cannot wait until we have achieved some semblance of consensus before readding the same content. This PNAS study simply fails every single notability test we normally employ in pharmacology articles. The fact that it's from a "reliable source" means nothing; there are 5206 other reliable sources about metformin, most of which are clinical studies and not Petri dish studies. I simply cannot understand why we should cover this single unconfirmed preliminary result, and I took several responses above to be in agreement with my view. I'm rapidly going towards having this page protected until the dispute has been resolved. JFW | T@lk 22:59, 11 March 2009 (UTC)

Sorry guys... JFW | T@lk 23:02, 11 March 2009 (UTC)

This study isn't suitable as it's an animal and cell study. How do you propose this relates to human subjects? I mention that because this is a human drug, not an animal one. Placing this on the article prior to a conclusive human study is tantamount to causing panic amongst our diabetic readers, and the danger of placing this here before a proper study has been conducted should not be underestimated. Please wait for a human study, just to enforce what I'm saying, please wait for a human study. There is no rush here. —Cyclonenim (talk · contribs · email) 23:41, 11 March 2009 (UTC)

Besides what JFW claims, the 2009 study was not just about petri dish it included mice as well. The 2008 one was on humans and it brings more evidence that Metformin monotherapy (without insulin) has increased Aβ than combined therapy. The problem with the 2008 study is that it used subjects with same levels of dementia as controls (similar Aβ is expected anyway). There's strong association of Beta amyloid with AD so precautionary principle applies. There's no need to anyone panic, no one is questioning the safety of combined Metformin+Insulin. If you think the information makes the article unbalanced add more of you think it's important. The negative POV is not to blame if it gains evidence only because the article is incomplete. I've no problem in moving it to another section like "Controversies", "Unclear effects", whatever, or to a rewriting, as long as the main information is preserved.--Nutriveg (talk) 02:23, 12 March 2009 (UTC)

You just stated the problem with both studies yourself. You stated that the 2008 one on humans used subjects with the same level of dementia as the control subjects, which immediately disqualifies that study as a good study on humans. The 2009 study is still based on mice and cells, which as we all know, is not the same as producing the same effect in a human. Until a later study which concludes the effect in humans, I'm very wary to add it to the article. It's not so much that it's negative, I don't mind putting negative POV stuff in articles, so long as it's reliable and above all relevant. This, however, is not relevant to humans and should be excluded until that has been fixed. —Cyclonenim (talk · contribs · email) 07:36, 12 March 2009 (UTC)

You shouldn't garbage the whole study because of that control issue (non-diabetics), since when comparing diabetics treatments on that same ground it shows that concomitant therapy performs better than monotherapy on beta amyloid, getting the same, but restated, conclusion of the 2009 one: monotherapy is worse than concomitant therapy. The comparative effect of monotherapy and concomitant on beta amyloid is supported by two studies, on three different approaches (cellular model, mice and humans). The AD association with beta amyloid may be omitted from the text, but the comparative effect of monotherapy on beta amyloid is enough supported, at least to use the Precautionary principle, which I'll cite since no one cares to read "The precautionary principle applies where scientific evidence is insufficient, inconclusive or uncertain and preliminary scientific evaluation indicates that there are reasonable grounds for concern that the potentially dangerous effects on the environment, human, animal or plant health may be inconsistent with the high level of protection chosen by the EU".Nutriveg (talk) 15:11, 12 March 2009 (UTC)

You continue to push for a line of evidence that simply does not exist. Perhaps the time has come for you to explain why you are so passionate about including this single study. There is no evidence that metformin use predisposes to dementia, and I actually find it quite irresponsible of you that you continue to push this. Metformin is the one antidiabetic drug known to reduce cardiovascular disease (UKPDS). Will you, because of your precautionary principle, deny these effects? Now you have come along with a theory that simply lacks a strong epidemiological evidence base and expect us to swallow it whole? You have now been opposed by four different editors, most of whom are very well acquainted with the rigors of evidence and the need to appraise single studies carefully. I urge you in the strongest terms to read WP:MEDRS, a guideline which explains clearly the kind of studies we would normally be citing in pharmacology articles. JFW | T@lk 21:13, 12 March 2009 (UTC)

For now I'm supporting the inclusion of the evidences brought by reliable sources that monotherapy is related to higher beta amyloid than concomitant therapy with insulin. But you're unable to see that as you were when you kept bashing it was just about "petri dish". If you want to investigate dementia alone I'd recommend another study which says that "Patients who were treated with oral antidiabetic medications" had higher risk for dementia then diabetes alone.--Nutriveg (talk) 21:46, 12 March 2009 (UTC)

Unless the full article so states that then your last sentence seems a synthesis, for the abstract makes no comment as to relative risks of diabetes and diabetes-treated with oral agents - yes differing hazzard ratios are stated, but I fail to see (in the abstract) whether one is statistically higher than the other. So unless the full article (to which I have not access) makes that comparison comment, then WP:SYN applies. Also note that WP:PRIMARY states "All interpretive claims, analyses, or synthetic claims about primary sources must be referenced to a secondary source, rather than original analysis of the primary-source material by Wikipedia editors." - and that's policy. So priliminary findings (assuming correctly reliably sourced) are generally not to be used until some secondary source assesses the significance or otherwise of the initial findings, and certainly not in list of adverse effects as there is no chance yet of any real-world consensus on this. Lastly wikipedia is not a news ticker-tape of unfolding events, but is at least somewhat set back waiting for a less myopic view (per Wikipedia:NOT#NEWS). David Ruben ^Talk 22:52, 12 March 2009 (UTC)

I'm just not feeling it, guys. There's too much speculation here: metformin might produce an effect in humans that might represent a greater risk for a disease that a person with well-treated diabetes might live long enough to develop.

Nutriveg, I think we all understand the precautionary principle. I think all the rest of us also recognize that Wikipedia's content policies are not controlled by the Maastricht Treaty. We need to represent the proportional weight of scientific evidence. The worry that "metformin might cause Alzheimer's" is simply not a significant enough issue to justify mentioning it at this time. WhatamIdoing (talk) 23:49, 12 March 2009 (UTC)

The paper does not demonstrate a causal link between metformin use and AD. At present, speculation of this nature is a fringe theory with only a single reference that does not merit entry in Wikipedia's article. Axl ¤ [Talk] 10:38, 13 March 2009 (UTC)

In vitro studies are not of enough significance to qualify for an article on a disease in humans for anything other than basic science. This might be appropriate for an article on ongoing research.--Doc James (talk · contribs · email) 03:40, 15 March 2009 (UTC)

Wiki said "increased risk of Alzheimer Disease" the ref said "increases biogenesis of Alzheimer's amyloid peptides". This ref says nothing about alzheimers disease just about amyloid peptides in petri dishes.--Doc James (talk · contribs · email) 03:45, 15 March 2009 (UTC)

Beta amyloid and Metformin monotherapy

The topic has changed I think you're unable to see my last addition. There's no mention of AD in it, but beta amyloid. It's not about Metformin, but "Metformin monotherapy". And it's not a single paper but two papers supporting the information. Read what you're talking about first.--Nutriveg (talk) 12:19, 13 March 2009 (UTC)

Since my last edit albeit many came here to comment on AD, all failed to comment on "Beta amyloid and Metformin monotherapy" as I exposed, "Axl" and "JFW" said it was a single study, but there are two supporting studies, "WhatamIdoing" commented about Alzheimer, but there's no mention of Alzheimer in my last edit, both "David Ruben" and "JFW" commented on dementia, there's no mention of dementia either. So, having all the comments made to points that were already removed from the text or ignored new information that has been added they are invalid for that last edit. So if no one express a valid argument about it I'll revert to that last edit.--Nutriveg (talk) 21:17, 13 March 2009 (UTC)

No, actually, I think you're going to pay attention to the utter lack of WP:Consensus for its inclusion, not to whether or not you think that the uniform opposition by many independent editors counts as "valid arguments" that persuade you to change your mind about the subject. WhatamIdoing (talk) 21:29, 13 March 2009 (UTC)

The edit link provided does include "diabetic dementia patients", so stop wikilawyering, stop pushing a (currently) minor research observation, and stop attacking other editors (discuss issues not editors), finally don't issue ultimatums of continuing to revert against consensus - that is not how we collaboratively work here and such action risks you being blocked for disruption. David Ruben ^Talk 14:52, 14 March 2009 (UTC)

It's more tricky to find the references that Nutriveg added, because the article has since been changed (reverted). Nutriveg's most recent edit is technically accurate. However it gives undue weight to a finding that requires a lot more research before it becomes relevant to Wikipedia's article. Axl ¤ [Talk] 17:41, 14 March 2009 (UTC)

"WhatamIdoing": just saying you disagree doesn't help reach consensus, I tried to improve the text listening to previous arguments. David, well those were the subject of the study (all of the subjects, including controls, had dementia), it isn't said there was a connection, I may remove that part. Axl, there are two articles supporting the information, while one includes two studies, and I moved the text from "side effects" to "interactions" (with insulin), so there's no undue balance. If three studies aren't enough why not to remove all the remaining text in the same situation but mine?--Nutriveg (talk) 19:18, 14 March 2009 (UTC)

Nutriveg, we're trying to write an encyclopedia, not a breaking-news website. This purported connection is widely considered to be speculative, perhaps worth more research -- but not known. Mentioning it at all is inappropriate at this time. When it hits the textbooks or the reviews, then we can include it. WhatamIdoing (talk) 19:40, 14 March 2009 (UTC)

Agree with WhatamIdoing. This is not significant until it hits a review.--Doc James (talk · contribs · email) 05:20, 15 March 2009 (UTC)

Adding some information:

Activation of AMPK inhibits amyloid beta production [6], Metformin activates AMPK [7].

Untreated diabetic patients with dementia had higher amyloid-beta peptide load in the cerebral cortex.[8] --Nutriveg (talk) 12:23, 17 April 2009 (UTC)

Have there been any further developments in this respect? Fvasconcellos (t·c) 21:06, 18 August 2009 (UTC)

At least one.--Nutriveg (talk) 21:29, 18 August 2009 (UTC)

I can't read this article but I think it's related [9]--Nutriveg (talk) 04:01, 19 August 2009 (UTC)

About women: "Metformin reduces the insulin response by decreasing hepatic gluconeogenesis and reducing androgen levels,"[10] "The results showed that (...) following metformin, (...) insulin response was significantly lower"[11] About men: "low early insulin response was associated with increased risk of subsequent Alzheimer’s disease" [12]. "A low insulin response at baseline was associated with a higher cumulative risk of AD"[13]--Nutriveg (talk) 04:19, 19 August 2009 (UTC)

Interesting. I'm sure someone will soon start looking for a direct link between metformin use and incidence of AD. Fvasconcellos (t·c) 12:39, 19 August 2009 (UTC)

"Increased levels of plasma Aβ 42 were found in non-demented subjects who used insulin and biguanides"[14]. That's a review.--Nutriveg (talk) 14:45, 6 October 2009 (UTC)

links

Trying to follow the above discussions, and would like to know if the following two links are part of the discussions?

1. Metformin
2. Metformin - Evidence from the UK Prospective Diabetes Study (UKPDS)

— Preceding unsigned comment added by Gioto (talk • contribs) 06:07, 17 April 2009 (UTC)

• The first link (adipocyte.co.uk) is run by a UK Individual and may be an interesting summary but is less useful as a source (see guidance of WP:RS and WP:PSTS). The web pages do point to a number of on-line publications that do look like useful sources however.
• The second link is to the NHS library but the particular summary of UKPDS is itself not a publication (not dated and no authors named) and does not provide links to the publications mentioned or provide full form references for them. For example the first reference given "(National Collaborating Centre for Chronic Conditions, 2008)" implies that there should be a bibliography supporting the summary but no bibliography is provided so the references cannot be verified.

—Teahot (talk) 09:48, 17 April 2009 (UTC)

Okay thanks for the explanation. I also found the following article "Metformin and serious adverse effects - The Medical Journal of Australia" and a more recent one Metformin and lactic acidosis in an Australian community setting: the Fremantle Diabetes Study which may need to be add if relevant. 02:32, 14 May 2009 (UTC)

Interesting; the latter could certainly be worked into the article. That adipocyte.co.uk link is actually very good. Although (as Teahot mentioned) it is not useful as a direct source as it is self-published, it provides and summarizes references that are reliable sources. Fvasconcellos (t·c) 14:04, 14 May 2009 (UTC)

Any direct references to published articles in the Medical Journal of Australia (including the two mentioned), would make excellent sources. If you think they are relevant, I suggest you go ahead and add them.—Teahot (talk) 17:40, 14 May 2009 (UTC)

Metformin and CD8 function

This study has been making waves in the popular press. It's much too early to add it to the article, but it's definitely something to keep an eye on. Fvasconcellos (t·c) 02:26, 11 June 2009 (UTC)

And: Metformin induces unique biological and molecular responses in triple negative breast cancer cells. Also still a mouse model, very preliminary as the AD research mentioned above, but something to keep an eye on. Fvasconcellos (t·c) 15:48, 12 September 2009 (UTC)

Reduced pancreatic cancer risk?

Will add to the article later. Fvasconcellos (t·c) 21:05, 18 August 2009 (UTC)

Thanks to the people who've worked on this article

I've recently been diagnosed with type2 and this has been really helpful. Your work is appreciated -Thanks! —Preceding unsigned comment added by 222.153.36.128 (talk) 11:11, 12 September 2009 (UTC)

I'm very glad to hear that, and I hope I speak for all contributors in saying "you're welcome". If you have any suggestions for improving the article, they're more than welcome. Fvasconcellos (t·c) 15:41, 12 September 2009 (UTC)

Reduced insulin response in women

The following phrase was removed but I don't see why:

In women, Metformin reduces insulin response by decreasing hepatic gluconeogenesis and reducing androgen levels.

--Nutriveg (talk) 13:58, 6 October 2009 (UTC)

There are a few problems with your addition. You added a tiny section under "adverse events", while I suspect you wanted to cite these studies as evidence of a beneficial effect. The data on PCOS is already discussed elsewhere in the article (under "off-label use"). Could I also suggest that 11 references to make the same point is also a bit excessive.

Could I recommend that you select 1-2 references that actually add anything to the article and place them in the relevant section (probably "mechanism of action"). JFW | T@lk 17:44, 6 October 2009 (UTC)

Well, I didn't create a new section but a new title under a existing section, to separate from the others. I do think that "reduced insulin response" is an unexpected effect, you may suggest a better section for that phrase.

I'm not talking about PCOS, but "reduced insulin response".

I didn't knew if your problem was with sources, since you said "these studies are not really of sufficient clinical relevance" as a justification to revert my edit, so I added other sources (including other studies) I had available that support that phrase.--Nutriveg (talk) 20:02, 6 October 2009 (UTC)

Since there's no further response so far I'll put it back.--Nutriveg (talk) 21:50, 13 October 2009 (UTC)

"Reduced insulin response" is, actually, neither adverse nor unexpected. It should be mentioned in the article, but not as an adverse effect, and certainly does not merit its own section. By the way, nearly all of those references deal with non-diabetic women with PCOS, in which this effect is beneficial, as hyperinsulinemia plays a major role in PCOS. Fvasconcellos (t·c) 22:37, 13 October 2009 (UTC)

I don't see why it would be expected to delay insulin response, but anyway it deserves citation. It's not a new section but a topic under a existing section, since that section is divided by topics. It's not adverse if one has PCOS but otherwise it increases the risk of Alzheimers.[15].--Nutriveg (talk) 14:42, 14 October 2009 (UTC)

Perhaps it's just your terminology that is nonstandard. Presumably by reduced insulin response you don't mean insulin resistance. Perhaps you should clarify your edits rather than simply reverting back against consensus. JFW | T@lk 21:52, 14 October 2009 (UTC)

I used the same term used by the sources, I just cited them, where they are clear to differentiate both, since insulin response can be affected by other factors. I didn't simple reverted back, I waited for your (lack of) response for more than a week!--Nutriveg (talk) 22:06, 14 October 2009 (UTC)

Evident lack of reliable source

Medical association sources are not reliable, because their primary interest is make profit. Metformin is low effective against diabetes, but it is sold JUST because it is more economically conveniet than testosterone (which is much safer and effectiver, try and see...).

It is clear why it is sold metformin and not testosterone: because it is necessary to take many tablets per day instead than one injection per month (testosterone).--158.194.199.13 (talk) 20:09, 28 October 2009 (UTC)

Please see WP:MEDRS for what actually constitutes a reliable source. Metformin is not "low effective against diabetes". In fact, it is probably the antidiabetic with the most well-established benefits; broadly speaking, all oral antidiabetics are equally effective in lowering blood sugar and Hb_A1C.

There is absolutely no high-quality evidence to support the safety or efficacy of testosterone replacement as a treatment for T2DM. At best, there is the possibility of its supplementation being somewhat beneficial in some men with diabetes.

And, finally, even if testosterone was an established treatment for diabetes, this information would not belong in the Metformin article. Please do not reinsert it. Fvasconcellos (t·c) 00:07, 29 October 2009 (UTC)

Reliable means non profit source. Medical associations are profit associations. There are no serious articles in which is visible an high metformin anti-diabetic effectiveness for a simple reason: it is not effective. If it is a common treatment for merely economic reasons is another fact.

Concerning to the testosterone there are many articles in which it is well explained that testosterone injictions greatly improve sugar tollerance (and of course erection, osteoporosis, anemia, memory and so on...). Testosterone is a good treatment for all T2M patients because they are hypogonadic, it is simply impossible to have type 2 diabetes with good free testosterone levels (>20 picograms/ml).

Testosterone is simply much effectivier and safer than metformin. Try and see!

I would suggest to write in the article:" In order to obtain the maximum profit metforin is sold as anti-diabetic drug. Metformin is unuseful and damaging anti-diabetic drugs. This compound is very effective just on increasing doctor and industries bank account...There are many better alteratives as in example testosterone, unfortunately (for the profit of industries) they must be injected just once per month (and also less)".--Testosterone vs diabetes (talk) 16:10, 29 October 2009 (UTC)

No, that is not what it means. Read WP:MEDRS for what constitutes a Reliable source for Wikipedia's medicine-related articles. There are no high-quality studies in peer-reviewed academic journals to support your suggestions. Metformin is one of the cheapest antidiabetics available (surpassed only by the old sulfonylureas) and is a generic anywhere in the world; trust me, it's no one's idea of a cash cow.

Please stop edit-warring; you're quickly headed for a block. Fvasconcellos (t·c) 17:33, 29 October 2009 (UTC)

It is absolutely false! If you control (even in Wikipedia articles) there are many articles in review with high impact factor related with high efficiency of testosterone in decreasing excessive blood glucose levels. Hypogonadism is very related with diabetes mellitus.

http://www.ncbi.nlm.nih.gov/pubmed/19444934?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

http://www.ncbi.nlm.nih.gov/pubmed/18832284?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

http://www.ncbi.nlm.nih.gov/pubmed/18832284?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

http://tde.sagepub.com/cgi/content/abstract/34/5_suppl/97S

http://www.ncbi.nlm.nih.gov/pubmed/18772488?ordinalpos=24&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

According to the scientific reviews: testosterone is definitely better than metformin as anti-diabetic drug (and of course as anti erectile disfunction, osteoporosis, Alzhaimer, dementia and so on). Metformin is better than testosterone from a merely economic point of view.

You simply can not accept that diabetes mellitus is easy to recover: just take testosterone in right dosage! You can not accept that metformin is not effective (a part on doctor's bank account of course).

Testosterone is very cheap (more than metformin), and with one injection per month (or also per trimester) diabetes is out. Metformin costs much more because it is also necessary to take many tabs per day.

The first sources in the article have not scientific value and they are not scientific articles, they are just pubblicity--Testosterone vs diabetes (talk) 17:55, 29 October 2009 (UTC)

The nature of a non-profit

Non-profit organizations such as the American Diabetes Association are so named because it is illegal for their members to profit from the organization. Consequently, the claim in the edit summary that "their primary aim is the profit" is absurd. WhatamIdoing (talk) 21:02, 29 October 2009 (UTC)

American Diabetes Association is a non profit association???? Do you know the huge deal of anti-diabetic drugs? Why this "non-profit" association speaks about highly remunerative drugs as metformine, or about highly remunerative foods as in example low colosterol food? Why American Diabetes Association make censorship about the real T2M cause (low testosterone and/or high cortisol levels)? I have never heard a doctor speaking about the tight relationships between these two hormones and diabetes (look upward articles). This is a proof that what is really important for industries is only the profit, not pubblic health! Sorry for my bad english, but I hope you understood. Why they try to prescribe metformin and not testosterone, when it is clear that the steroid is much better?--Testosterone vs diabetes (talk) 21:18, 29 October 2009 (UTC)

Where are the interventional trials showing testosterone to decrease micro- and macrovascular disease? JFW | T@lk 21:42, 29 October 2009 (UTC)

Yes: American Diabetes Association, IRS number 13-1623888, Pub 78 listed is a public charity (the highest classification of non-profit organization under US laws).

I don't know why you think that they favor "highly remunerative" drugs and foods. Metformin is quite cheap -- about 20 cents per pill for a low dose, which means that a low dose of the typical daily testosterone creams used in the US costs about ten times as much -- and naturally cholesterol-free foods (e.g., vegetables and rice) are cheaper than high-cholesterol foods (e.g., pork). Even if they weren't cheaper, they make no money from those recommendations.

Additionally, I suspect that many women would object to being given testosterone, especially women with polycystic ovarian syndrome, who naturally overproduce testosterone and related androgens, and find that testosterone hurts, not helps, their health. Too much testosterone causes acne, hirsuitism, and infertility in women.

Do please provide JFW with information about the proper clinical trials that you say support your unusual beliefs. WhatamIdoing (talk) 22:06, 29 October 2009 (UTC)

Are you blind? Do you see the articles upward? Is it cheaper testosterone (one injection evert TRE MOUNTHS) or metformin (many uneffective tablets per day)? Is cheaper normal cheese or cheese with a low cholesterol content? Is cheaper normal yogurt or yogurt with low cholesterol content? American diabetes society is a merely profit association which promotes use of expensive and uneffective products as metformin (uneffective but economically convenient), low colesterol food (total colesterol is not related with cardio-vascular diseases or diabetes). American society of diabetes makes censorship about the real causes of diabetes type 2 (low testosterone levels and/or high cortisol levels), the economic reasons are clear.

JFW is a doctor. It means he is payed to prescribe metformin, therefore he get blind (he do not see the articles in this discussion). His opinion is not important because he has interest to defend metformin.

Whatiamdoing, testosterone can not cause acne and hyrsitism, you are making confusion between testosterone and dihydrotestosterone. Bald people for example have low testosterone levels and high dihydrotestosterone levels. The effects oh these hormones are completely different, testosterone acts especially improving sugar absoption and increasing muscle mass (for that reasons diabetic patients have low muscle mass).

There are many way to take testosterone, each of them has vantages and disdventages. For diabetes the intramuscolar injections are better than gels. The injections are very cheap, gels are not cheap.

The role of testosterone in women sugar absorption is not well studied, therefore we can not make easy conclusion, however this hormone is very important for women too, women testosterone replacement therapy is very effective against loss of libido and osteoporosis. If you see the articles the use of testosterone is effective and safe for men, further studies are necessary to be done for woman patients.

Metformin is uneffective and damaging drug, it is sold just because is very remunerative. --Testosterone vs diabetes (talk) 17:30, 30 October 2009 (UTC)

Perhaps things are different in your country, but here in the US, fat-free yogurt cost exactly the same as low-fat yogurt, and full-fat yogurt is very expensive (raises the cost by 30% to 60%) and can be hard to find. Reduced fat cheeses, e.g., part-skim mozzarella, are the cheapest on the market. Skim (fat-free) milk is 5%-10% cheaper than whole milk.

Perhaps testosterone is also cheap in your country. It is very definitely not cheap in the US. Metformin, on the other hand, is widely available in the US for just $10 for a 90-day supply. See here. WhatamIdoing (talk) 22:40, 30 October 2009 (UTC)

In Brazil, a 30-day supply of metformin costs about 50 cents of a dollar through a government program (Farmácia Popular) and about 4 dollars otherwise. Interestingly, low-fat yogurt is no more expensive here either :) Fvasconcellos (t·c) 22:44, 30 October 2009 (UTC)

In Italy Sustanon 250 (testosterone injections, usually one per 3-4 moths) cost 11 euro. It means 11/100 (days)= 0.11 euro per day.

Metformin 1g costs 5 euro (60 tabs. Usually 3 tabs per day)= 0.25 euro per day.

Testosterone is definitely cheaper than metformin! Moreover testosterone is effective against osteoporosis, loss of libido, depression, dementia, blood pressure normalization; metofmin no. Testosterone has also less side effects than metformin. --Testosterone vs diabetes (talk) 15:01, 1 November 2009 (UTC)

Interesting information. Unfortunately there is no proof, and no reliable source claiming that testosterone is a better therapy overall -it has been suggested that could be of some help in hypogonadal men. And such information plays no role in this article. --Cyclopia^talk 15:04, 1 November 2009 (UTC)

I agree: for any alternative treatment to be relevant to this particular article, we would have to have a study that directly compared the two options. WhatamIdoing (talk) 01:44, 2 November 2009 (UTC)

Why Wikipedia makes censorship and defend profits?

It is clear that Wikipedia does its best to increase the profit of the industries of medicines:

• The administrators/users, in order to improve the profit of industries, try to delete the scientific articles that speak about the real causes of diabetes mellitus type 2 (no diet or fat): sublclinical Cushing's syndrome and testosterone deficiency!

• The administrators/users get blind claiming that there are not articles about the correlations between cortisol/testosterone and diabetes. Instead there are several article (just look upward and in diabetes mellitus article), they just do not want to see because they are payed to say that.

• The administrators insert completely false informations, as correlationships between cholesterol and diabetes (where are the articles?)

• The administrators do not want that the big pubblic knows the evidence: testosterone is much safer and effectivier than metformin for DT2 cure (try and see).

Think as you want, but the evidences are clear.--Testosterone vs diabetes (talk) 18:51, 30 October 2009 (UTC)

• TvD, the point is simple: you have not provided one single reliable source which states your point of view. Not one. The sources above don't say anything of the like: at the very best, they suggest that testosterone is investigated as possibly being of help in solving diabete issues in hypogonadal men. That's it. Now please stop throwing around nonsense conspiracy theories and remember that this is not the place where to promote your personal causes. --Cyclopia^talk 21:52, 30 October 2009 (UTC)
  • Exactly. The evidence is indeed clear. As for your assertions above I, for one, am not paid a dime to edit Wikipedia (Big Pharma can't afford me :). No one has denied that corticosteroids and testosterone play a role in DM. And, if the overwhelming scientific evidence in any decent textbook or review is not enough, try reading about the UKPDS, for instance, and then let me know what you think about (1) the influence of diet or weight on the development of diabetes and (2) the efficacy of metformin (and other antidiabetics). Fvasconcellos (t·c) 22:51, 30 October 2009 (UTC)

It is interesting to note that the citations you show make omerta regarding cortisol and testosterone, however I took patience and read it.

There are no direct correlations between diet and T2M, we can say that low carb diet is very dangerous for diabetic patiens, because it increases cortisol levels (cortisol proctect the body from hypoglyceamia) and therefore insulin resistance. We can state that it is necessary to have an equilibrated diet, every kind of excess or deficiency is harmful.

There are correlations between fat (especially abdominal fat) and D2T. One of my citations speaks about increase of intecellular adypocytes cortisol level, because these cells increase cortisol and estogens (estrogens derive from testosterone, therefore excessive estrogens levels can lead to testosterone deficiency), therefore we can state that excessive fat can worse hypogonadism and subclinical Cushing's syndrome. We also can say that hypogonadism and subclinical Cushing's syndrome can lead to excessive accumulation of abdominal fat (it is a classical vicious circle...).--Testosterone vs diabetes (talk) 15:01, 1 November 2009 (UTC)

TvD, your hypotheses are not scientific consensus, accept it. We cannot put non-consensual hypothesis and handwaving synthesis on an encyclopedia. If you feel compelled to inform the world of your theories about diabetes, open your own website. --Cyclopia^talk 15:06, 1 November 2009 (UTC)

These are not my theories, you can find that "theories" in every book of endocrinology--Testosterone vs diabetes (talk) 15:24, 1 November 2009 (UTC)

Oddly enough, the latest scientific reviews disagree with you -see discussion on the diabetes mellitus talk page. I am going trust more the latter, sorry. --Cyclopia^talk 15:26, 1 November 2009 (UTC)

The latest article in the discussion? Where it disagrees with me?--Testosterone vs diabetes (talk) 15:46, 1 November 2009 (UTC)

is link to Drugs@FDA clinical/lable info part of template? nice addition

Drugs@ FDA has a bunch of scanned things used to support license and label. Note I have an agenda here, I'm trying to get more people to use this and have FDA stop accepting scanned documents without some attempt at OCR equivalents,http://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020357a_s006.pdf Their site also makes use of posts and generic links making citations hard so I'm encouraging anyone who finds this useful to suggest they make the site better for online usage, including maybe an API. While this is clearly soapboxing, it is quite relevant to the goals of wikipedia. http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/ is the main search page and everything from then on seems to use cookies and can't book mark... Nerdseeksblonde (talk) 15:56, 1 November 2009 (UTC)

12 papers on pubmed mention "diabetes cushing testosterone" for debate above,

1. Nakamura, A; Nagai, S; Taniguchi, S; Umetsu, M; Atsumi, T; Wada, N; Yoshioka, N; Ono, Y; Sasano, H; Koike, T (Jan-2007). "Unilateral adrenalectomy improves insulin resistance and polycystic ovaries in a middle-aged woman with virilizing adrenocortical adenoma complicated with Cushing's syndrome". Journal of endocrinological investigation. 30 (1): 65–9. PMID 17318025. {{cite journal}}: Check date values in: |date= (help)CS1 maint: date and year (link)
2. Glintborg, D; Andersen, M; Hagen, C; Hangaard, J; Rasmussen, PE; Schousboe, K; Hermann, AP (Dec-2004). "Prevalence of endocrine diseases and abnormal glucose tolerance tests in 340 Caucasian premenopausal women with hirsutism as the referral diagnosis". Fertility and sterility. 82 (6): 1570–9. doi:10.1016/j.fertnstert.2004.06.040. PMC 10.1016/j.fertnstert.2004.06.040. PMID 15589862. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help)CS1 maint: date and year (link)
3. Afandi, B; Saadi, HF. "Cushing's syndrome caused by unsupervised use of ocular glucocorticoids". Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 9 (6): 526–9. PMID 14715481.
4. Fukushima, A; Tanikawa, T; Kawahara, C; Misawa, H; Kanda, K; Morita, E; Sasano, H; Tanaka, Y (Apr-2003). "Virilizing adrenocortical adenoma with Cushing's syndrome, thyroid papillary carcinoma and hypergastrinemia in a middle-aged woman". Endocrine journal. 50 (2): 179–87. PMID 12803238. {{cite journal}}: Check date values in: |date= (help)CS1 maint: date and year (link)
5. Lubin, V; Antoine, JM; Beressi, JP; Vexiau, P (9-Nov-2002). "[Cushing's syndrome during pregnancy]". Presse médicale (Paris, France : 1983). 31 (36): 1706–13. PMID 12467153. {{cite journal}}: Check date values in: |date= (help)CS1 maint: date and year (link)
6. Petruson, K; Petruson, B; Lindstedt, G; Bengtsson, BA (Jul-1997). "Transsphenoidal adenomectomy in Cushing's disease via a lateral rhinotomy approach". Surgical neurology. 48 (1): 37–43, discussion 44-5. PMID 9199682. {{cite journal}}: Check date values in: |date= (help)CS1 maint: date and year (link)
7. Bakiri, F; Aouali, R; Semrouni, M; Derome, P; Chitour, F; Benmiloud, M (Oct-1996). "Treatment of Cushing's disease by transsphenoidal, pituitary microsurgery: prognosis factors and long-term follow-up". Journal of endocrinological investigation. 19 (9): 572–80. PMID 8957739. {{cite journal}}: Check date values in: |date= (help)CS1 maint: date and year (link)
8. Cunningham, SK (Dec-1994). "Dissociation of adrenal androgen and cortisol secretion in Cushing's syndrome". Clinical endocrinology. 41 (6): 795–800. PMID 7889616. {{cite journal}}: Check date values in: |date= (help)CS1 maint: date and year (link)
9. Trainer, PJ; Verhelst, J; Howlett, TA; Lowe, DG; Grossman, AB; Savage, MO; Afshar, F; Besser, GM (Jan-1993). "Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successful treatment". Clinical endocrinology. 38 (1): 73–8. PMID 8435888. {{cite journal}}: Check date values in: |date= (help)CS1 maint: date and year (link)
10. Malchoff, CD; DeBold, CR; Kozol, RA; Ramsby, GR; Page, DL; Malchoff, DM; Orth, DN (Apr-1989). "Adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia: an unusual cause of Cushing's syndrome". The Journal of clinical endocrinology and metabolism. 68 (4): 855–60. PMID 2537845. {{cite journal}}: Check date values in: |date= (help)CS1 maint: date and year (link)
11. Bezverkhaia, TP; Verkhogliadova, LM; Babicheva, ZI; Kovalenko, IV (1986). "[Diagnostic value of determining the levels of testosterone, estradiol and testosterone-estradiol-binding globulin in the plasma]". Laboratornoe delo (6): 330–3. PMID 2427774.{{cite journal}}: CS1 maint: date and year (link)
12. Baba, H (20-Jan-1973). "[Radioimmunoassay of serum testosterone--results of the study of normal subjects and patients with endocrine disorders]". Nippon Naibunpi Gakkai zasshi. 49 (1): 60–79. PMID 4734772. {{cite journal}}: Check date values in: |date= (help)CS1 maint: date and year (link)

I've appreciated your edit. But the text you added is partially related with diabetes mellitus. Adrenocortical adenomas can cause DM but they are quite rare, and their percentage in subclinical Cushing's syndrome and in diabetes mellitus is quite low. Usually patients with diabetes mellitus type 2 or with subclinical Cushing's syndrome have higher (than normal individuals) cortisol levels, higher ACTH levels (with possibilities of pituitary adenomas) and lower testosterone levels.--Testosterone vs diabetes (talk) 16:55, 1 November 2009 (UTC)

The other articles seem very interesting! --Testosterone vs diabetes (talk) 16:55, 1 November 2009 (UTC)

abs copy vio? link? is this a wikipedia thing or legal? I don't have an easy way to edit but what is fair use? I thought anyone could index these or replay pubmed. Nerdseeksblonde (talk) 17:59, 1 November 2009 (UTC)

I don't think that abstracts are considered fair use. PubMed (ISI, Scirus etc.) is authorized to do so by the journals, but I doubt that non-open access journals are happy to see dozens of them freely distributed. Thus I erred on the side of caution. I personally hate this kind of things, but copyvios are legal stuff, and as such is taken pretty seriously here. It can be a good idea to ask to WP:MCQ (even if this stuff is just text, they probably have sound advice). Sorry if it caused problems. --Cyclopia^talk 18:13, 1 November 2009 (UTC)

I fixed the formatting of the list for you. When you're not trying to make the citations appear elsewhere on the page, just leave off the <ref> part. WhatamIdoing (talk) 01:49, 2 November 2009 (UTC)

TvD, some of these sources are interesting, but what do they have to do with metformin? For this article, we need studies that specifically and directly tell us something about metformin. This is Metformin, not Diabetes treatment. WhatamIdoing (talk) 01:52, 2 November 2009 (UTC)

We won't find them, because there hasn't been enough study in this area. Most of the studies above are not germane to this discussion (or the discussion at Diabetes mellitus for that matter). This whole discussion has meandered way off topic, and I'm inclined to collapse it. Fvasconcellos (t·c) 10:43, 2 November 2009 (UTC)

In this case, esp considering the size of above citation list, I wouldn't object but merit discussions can help add perspective to content. In this case, someone specifically has an issue with sources, withouth a big concern for relevance to this topic. "Metformin cushing" returns a tractable 6 refs,

Heneghan, Marykathleen (22-Sep-2009). "Cushing disease as possible cause of persistent growth failure despite growth hormone therapy in a small for gestational age male". Pituitary: -. doi:10.1007/s11102-009-0201-3. PMC 10.1007/s11102-009-0201-3. PMID 19771523. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help)CS1 maint: date and year (link)

August, P; Brooks, MM; Hardison, RM; Kelsey, SF; MacGregor, JM; Orchard, TJ; Chaitman, BR; Genuth, SM; Goldberg, SH; Hlatky, MA; Jones, TL; Molitch, ME; Nesto, RW; Sako, EY; Sobel, BE (11-Jun-2009). "A randomized trial of therapies for type 2 diabetes and coronary artery disease". The New England journal of medicine. 360 (24): 2503–15. doi:10.1056/NEJMoa0805796. PMC 10.1056/NEJMoa0805796. PMID 19502645. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help); Missing |author1= (help)CS1 maint: date and year (link)

Pop-Busui, R; Lopes, N; Jones, TL (Mar-2009). "Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort". Journal of the peripheral nervous system : JPNS. 14 (1): 1–13. doi:10.1111/j.1529-8027.2009.00200.x. PMC 10.1111/j.1529-8027.2009.00200.x. PMID 19335534. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help)CS1 maint: date and year (link)

Mapas-Dimaya, AC; Bahtiyar, G; Mejia, JO; Sacerdote, AS (Oct-2008). "Metformin-responsive classic salt-losing congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a case report". Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 14 (7): 889–91. PMID 18996819. {{cite journal}}: Check date values in: |date= (help)CS1 maint: date and year (link)

Iwasaki, Y; Nishiyama, M; Tsugita, M; Taguchi, T; Asai, M; Yoshida, M; Kambayashi, M; Hashimoto, K (26-Mar-2008). "Is the metabolic syndrome an intracellular Cushing state? Effects of multiple humoral factors on the transcriptional activity of the hepatic glucocorticoid-activating enzyme (11beta-hydroxysteroid dehydrogenase type 1) gene". Molecular and cellular endocrinology. 285 (1–2): 10–8. doi:10.1016/j.mce.2008.01.012. PMC 10.1016/j.mce.2008.01.012. PMID 18313835. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help)CS1 maint: date and year (link)

Christ-Crain, M; Lolli, F; Fekete, C; Seboek, D; Wittmann, G; Feltrin, D; Igreja, SC; Ajodha, S; Harvey-White, J; Kunos, G; Müller, B; Pralong, F; Aubert, G; Arnaldi, G; Giacchetti, G; Boscaro, M; Grossman, AB; Korbonits, M (Jun-2008). "AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome". The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 22 (6): 1672–83. doi:10.1096/fj.07-094144. PMC 10.1096/fj.07-094144. PMID 18198220. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help)CS1 maint: date and year (link) CS1 maint: unflagged free DOI (link)

Nerdseeksblonde (talk) 15:42, 2 November 2009 (UTC)

I have not inserted the articles. I try to find some study comparing testosterone and metformin.--Testosterone vs diabetes (talk) 16:28, 2 November 2009 (UTC)

Metformin vs testosterone

I did not find articles with strict comparations between metformin and testosterone treatments against diabetes.

http://www.ncbi.nlm.nih.gov/pubmed/12235466?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=2

http://www.ncbi.nlm.nih.gov/pubmed/11707532?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=14

Anyway metformin decreases testosterone levels, this effect (as earlier stated) can cause or worse diabetes (and many other diseases related to hypogonadism). We may therefore state that metformin is harmful for sugar absorption and many other health issues (bone density, sexuality, memory, cognition, mood, digestion...). Testosterone has no so serious side effects, and greatly improves the upward biological parameters (see diabetes mellitus and testosterone replacement therapy).

Testosterone is a natural product, metformin no (I mean it is not naturally present in the human body). Metformin failed to cure diabetes, testosterone (right now) no.

Metformin decreases TSH respond and may cause serious digestion problems (vomit, nausea, diarrhea, constipation), testosterone no.

We may therefore state that testosterone is definitely a better anti-diabetic drug than metformin.--Testosterone vs diabetes (talk) 19:05, 2 November 2009 (UTC)

This is interesting. But while the effects on the hormonal balance can be added per the sources you brought, the "statements" you talk about definitely cannot be added in any Wikipedia article, because at least they are a mix of WP:OR and WP:SYNTHESIS. The point is: we cannot write deductions that are not explictly stated in reliable sources (no matter how trivial they may seem -and here they do not seem trivial at all, too) --Cyclopia^talk 19:12, 2 November 2009 (UTC)

Of course, right now (in a wikipedia article) we can not state that testosterone is better than metformin aqs anti-diabetic drug. But, i guess, we can compare the anti-diabetic drugs as I did it upward using scientific articles in some specific paragraph.--Testosterone vs diabetes (talk) 19:19, 2 November 2009 (UTC)

I have nothing against the proposal. It doesn't seem to belong to this article, but a general "Comparison of anti-diabetic drugs", separated article, could be interesting, if well done and not limited to metformin and testosterone (I guess there are others). A good idea -that also allows you to learn Wikisyntax etc. and doing useful work- could be for you to work on it on a subpage on your userpage (see WP:SUB for details). After it reaches a "reasonably good" state, you can then move it to the article space. --Cyclopia^talk 19:44, 2 November 2009 (UTC)

There's already an article on that subject: Diabetes management.

The two papers linked above could be used in this article to supporta claim that metformin reduces testosterone levels in men. That's as far as we can go with it, because there's no evidence that this change has any practical consequences.

We also can't support this claim that testosterone is essentially safe, as it definitely has known side effects[16], some of which are considered severe. WhatamIdoing (talk) 04:52, 3 November 2009 (UTC)

Furthermore, testosterone is not an established anti-diabetic, and should not be presented as such (e.g. by including it in the Anti-diabetic drug article). There have been no head-to-head comparisons of testosterone and anti-diabetics, and comparing testosterone to these drugs will invariably be a synthesis of published material. Fvasconcellos (t·c) 10:02, 3 November 2009 (UTC)

I don't want to speak to merit in this discussion but certainly for wikipedia OR is a concern. Just generally there is a problem in the field to extrapolate results and assume causality where none exists. Also, there was something about "natural" above- AFAIK there is no magic here and natural doesn't have any inherent implications on safety and efficay for a specific purpose. Nerdseeksblonde (talk) 14:40, 3 November 2009 (UTC)

Whatamidoing the reduction of testosterone (hypogonadism) is strictly related with T2D, osteoporosis, memory loss, heart attacks and many other severe diseases (at least in men but it seems in women too). Metformin is dangerous for health because it reduces testosterone and tiroid's hormones.

Testosterone is a fully established anti-diabetes compound (up to now for men only), it is used by many doctors in USA and in EU excatly (also) for this purpose, its anti-diabetic use is greatly increasing. In example Dot. Ullis (who follows american olympic athlets and who write a book called "SuperT") uses testosterone for diabetic men (type 1 and 2). WhatamIdoing I invite you to do not attach absourd and nonscientific links with absourd and ridicolous (headache...hahaha...do not take offence) side effects. Yes testosterone can have serious side effects (mainly inhibition of endogenous T production) but absolutely not severe and anyway, metformin has much more side effects.

Metformin is not efficient in diabetes reduction for a simple reason: it does not affect insulin resistance. Metformin reduces gluconeogenesis (which is indeed one of the mechanisms involved in hyperglycemia), but it does not increase insulin respond (glucose absorption). Yes it (slightly...) reduces blood glucose levels, but this has nothing to do with diabetes or with insulin resistance. Diabetes is not excatly hyperglycemia, but it is intracellular glucose deficiency. I've never read (I could do a mistake in this) that metformin increases intracellular glucose levels, instead there are many articles stating the increase of insulin respond after using testosterone.

If a diabetic man takes metformin will not improve his health, if he takes testosterone will greatly improve his health.

Here the adjective "natural" means naturally present in human body (as testosterone in example) and nonnaturally present in human body (metformin is a natural compound but it is not naturally present in the human body). I think if something is similar to our natural compounds, it should be more effective and safer.--Testosterone vs diabetes (talk) 19:27, 3 November 2009 (UTC)

1)This place is not a forum to discuss about medicine, but it is for discussion on what has to be included in the article.

2)All of this would be interesting on a forum, but not here. It has been already repeated several times that what you are reporting above is either your personal opinion, or synthesis between sources. Therefore, it has no place in Wikipedia -and more so, not in this article.

Going into the details:

3) Testosterone is by no means a "fully established" anti-diabetes compound, at least unless sources are found showing academic consensus on that.

4) Your opinion on metformin effectiveness has to be backed up by sources explicitly stating what you say, otherwise, again, it is WP:SYNTHESIS

5) The widespread misconception that if something is "similar to our natural compounds, it should be more effective and safer" is a known falsehood. In our stomachs we have HCl, but you wouldn't want to drink it regularly. Hormones are extremly biologically powerful compounds and taking them without extreme precaution can create a lot of harm. And again, since it is what you think, it is WP:OR

6) Since these points have been repeatedly established, I invite our fellow Testosterone_vs_diabetes to drop the stick on the dead horse and to understand that this is not a soapbox. I invite him/her to collaborate constructively by providing sources and discussing them here, and eventually adding statements that are a)firmly and explicitly backed up by sources b)scientifically consensual. But this article is not going to say that testosterone is better than metformin, because 1)it is not backed up by sources 2)even if it was, it is not the right place to include such information.

I hope we can put an end to this debate. --Cyclopia^talk 19:56, 3 November 2009 (UTC)

Cyclopia there is the full consensus for testosterone use against diabetes. You also inserted articles focused on this topic. Testosterone is used by many doctors for clinical (not research only).

The scientific articles state that metformin reduces testosterone, LH and tiroid hormones. I think it is a very serious side-effect.

I'm perfectly agree with the other points, indeed it is not so serious to make an head to head comparation, but as you told it could be possible to speak about all anti-diabetic drugs.--Testosterone vs diabetes (talk) 20:10, 3 November 2009 (UTC)

there is the full consensus for testosterone use against diabetes. - Find a review paper stating that explicitly and I will agree. --Cyclopia^talk 20:13, 3 November 2009 (UTC)

The literature says that metformin produces lower levels of these hormones in men. The literature then says "The clinical significance of these findings needs further investigation" (PMID 12235466) -- that is, "We don't know if this has practical effects."

For example: There are drugs that dramatically increase the white blood cell count. Taking these drugs does not, however, produce leukemia. It's just a temporary and harmless artifact.

The scientific establishment has determined that metformin reduces these hormones. They have not determined that reducing these hormones this way has any practical health consequences.

You and I might believe that it's probable that there will be practical health consequences, but we have no reliable sources that say that reducing these hormones by taking metformin (and not due to any other cause) is a problem. WhatamIdoing (talk) 20:20, 3 November 2009 (UTC)

About the "headache" joke: You might choose to read the source again. The SEVERE side effects are listed thus: "Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); breast growth or pain; change in the size or shape of the testicles; dark urine or light-colored bowel movements; depression or mood changes; dizziness; gingivitis; interrupted breathing while sleeping; loss of appetite; nausea; painful or prolonged erection; stomach pain; swelling of the ankles or legs; urination problems; weight gain; yellowing of the skin or eyes."

IMO, anaphylaxis, kidney failure, liver failure, etc. are not jokes. People die from these side effects. WhatamIdoing (talk) 20:22, 3 November 2009 (UTC)

Ok, whatamidoing, I understand you perfectly...The side affects of your source are completely wrong! Testosterone does not cause that side effects (in case find articles, but I'm very sceptic). Talking seriously testosterone can have other side effects (inhibition of T endogenous synthesis, reduction of testicular volume. In some individuals is possible to have gynecomastia (effect due to estrogens which are testosterone derivatives, problem easily solved by anastrozol) and baldness (effect due to dihydrotestosterone, another testosterone derivative, problem easily solved by finasteride)

Conserning to the value of this testosterone (and other hormones too) reduction, I'm agree we have not clear results on it, on the other hand we have no reasons to think that this testosterone and TSH minor respond are different than others.

The anti-sexual effect of metformin was not studied because the people who take it have already erectile disfunction [PMID: 18727737] (it is almost impossible to have T2M with good free testosterone levels), therefore they do not recognize this effect.

I've found on internet a 30 years old user that took metformin and he started to have sexual problems http://www.progettodiabete.org/indice_ie1000.html?expert/2008/e2_02962.html

"Tre mesi fa ho ricevuto la diagnosi di IGT, e mi è stato prescritto del Metforal 500 (ora 3 compresse al giorno). Sto rapidamente riacquistando il pesoforma, a fronte di qualche banale disordine intestinale di cui ero stato avvisato. Purtroppo però, da quando ho incominciato ad assumere il Metforal ho notato una notevole diminuzione della libido: nessun problema erettile, direi piuttosto un disinteresse per l’attività sessuale."

(tre moths ago I've got IGT diagnosis, Metforal 500 (metformin) was prescribed to me (now 3 tabs per day). I'm rapidly getting the right weight, but with some intestinal disorder which I knew before. Unfortunatley, I had a strong libido decrease after Metforal use: no erectile problems, but disinterest for sexual activity).

Cyclopia, are the articles that we inserted good enough for that purpose? Is the book of Dot. Ullis a reliable source? Are the articles in a gym review reliable sources (in italian...)?--Testosterone vs diabetes (talk) 21:02, 3 November 2009 (UTC)

About WhatamIdoing concerns: If you think his source is wrong, find another source of equal reliability contradicting it.

About sources: For sure a forum about diabetes, like the one you translated, is not a RS. The "sources above" are also not good enough because -to my understanding- there is not a sentence saying explicitly that it is universally accepted as a cure. If I am wrong. quote it and link it. The book of Dr.Ullis, I don't know it, so please provide a link or more information -if it is an academic book (like a collection of reviews or an academic manual), may be. Articles in a "gym review" (??) don't look like a RS, but provide links to be sure. In short: I would consider RS recent, peer-reviewed academic reviews published in a decent-impact journal; possibly more than one. --Cyclopia^talk 21:11, 3 November 2009 (UTC)

Cyclopia, I accept the statements made by PMID 12235466. The statements made by this source are significantly smaller than the statements made by TvD. The source says that metformin (1) reduces several hormone levels (2) in men (3) in a short-term study involving a (4) very small sample size. The source also plainly and directly states that they don't know whether the lowered hormone levels produces the negative effects of hypogonadism. Thus I would support inclusion of an adverse effect: "reduced hormone levels in some men", but not anything further (e.g., "testosterone is definitely a better anti-diabetic drug than metformin").

TvD, the list of testosterone side effects comes from the US FDA's mandatory labeling for these products. The FDA is notorious for prohibiting manufacturers from mentioning any side effect that isn't proven to the FDA's satisfaction. It does not say that these are common side effects -- only that these severe side effects happen often enough for the FDA to require the manufacturer to disclose their existence to patients. WhatamIdoing (talk) 22:48, 3 November 2009 (UTC)

WhatamIdoing, sorry but it was me being not clear -I was answering to TvD concerns about you, not to you, sorry! --Cyclopia^talk 11:43, 4 November 2009 (UTC)

The list of your side effects is completely invented, do you have real scientific articles? FDA is a nonscientific source, and moreover its interests (to sell or to do not sell medicines) are too high to assume its good faith. FDA invent absoud T side effect in order to sell more remunerative drugs as in example metformin. Anyway here only scientific articles can be taken in consideration, it means your citation can not be considered. I've readen many testosterone articles and I know personally many testosterone users, I can ensure you the effects of your nonscientific source are really invented. Testosterone use can have serious side effects, but not severe. See testosterone mandatory sheets. Many people can not take metformin (because they vomit or have diahrrea), everyone can take testosterone.

Metformin is not a good anti/diabetic drug, testosterone yes. Metformin failed to cope diabetes, testosterone no.

I guess you are woman, testosterone is used in women too in order to cope osteoporosis and loss of libido (testosterone is essential in women too). Testosterone is not exactly a man hormone. --Testosterone vs diabetes (talk) 10:01, 4 November 2009 (UTC)

TvD, even if you were completely right (and while the side effects source above is indeed not the best, you have showed no proof of your position either), testosterone is not going to be mentioned here, because it is, at the very best, highly WP:UNDUE. --Cyclopia^talk 11:57, 4 November 2009 (UTC)

I guess if you can find a reliable source that uses both the words "metfomin" and "testosterone" you could argue for some passing mention but it is unlikely to be favorable or comprehensive (" some others have examined blah[]"). Personally I'm big on inclusion but then you need to argue over wording. Nerdseeksblonde (talk) 13:17, 4 November 2009 (UTC)

I can find good data only for women, comparing with oral contraceptive pill [17].--Nutriveg (talk) 13:30, 4 November 2009 (UTC)

And this which I can't call good enough.--Nutriveg (talk) 13:46, 4 November 2009 (UTC)

Although insulin sensitivity is associated with testosterone deficiency, there is no evidence that insulin sensitizers, including metformin and thiazolidinediones, are able to elevate testosterone levels in men with diabetes.--Nutriveg (talk) 13:52, 4 November 2009 (UTC)

"at least after 3-month treatment, metformin and dexfenfluramine do not modify the effects of diet on anthropometric, metabolic and hormonal parameters"--Nutriveg (talk) 14:05, 4 November 2009 (UTC)

Nutriveg, 3 of 4 our citations state that metformin reduces total and free testosterone (another one state that do not increase testosterone levels. What means? reduction?). Moreover metformin reduces Thyrotropin levels http://jcem.endojournals.org/cgi/content/full/91/1/225. Reduction of testosterone and TSH levels are very serious concerns.

Moreover I would remeber that metformin does not increase sugar absorption, it means metformin does not reduce insulin resistance.

Metformin is a not universally stated cure against T2M--Testosterone vs diabetes (talk) 17:00, 4 November 2009 (UTC)

Let's see if this makes more sense:

• YES: A substantial reduction of testosterone is usually a health problem.
• YES: Metformin reduces testosterone in some men.
• NO: Reduction of testosterone caused by metformin are very serious concerns.

We cannot make the last claim -- the claim that adds up the two previous ones as if they were algebraic equations -- because we have no reliable source that says exactly that. We have sources that say an unnaturally low testosterone level is a health problem. We have a source that says metformin reduces testosterone in some men. We do not have a source that this specific method of hormone reduction is a very serious concern. In fact, we have a source that says they're aren't sure if this particular reduction is actually associated with health effects. Therefore we cannot include a claim that they "definitely are", because we don't know that. We suspect it might be a problem, and you apparently believe it is a problem -- but we have no source that says that this effect creates practical health problems. We cannot go beyond our sources. WhatamIdoing (talk) 18:19, 4 November 2009 (UTC)

For me a 30 years old boy who have had sexual problems by metformin is a reliable source, and I'm sure there are many others.

What means "unnaturally low testosterone level"? Hypogonadism is not natural? Hypogonadism is very common and, unfortunately it is natural too. We have many user that have serious problems of hormones given by metformin (testosterone, LH and TSH levels), their reduction is always a serious problem. We have no reasons to think that "metformin hypogonadism or hypotyroidism" are different than others, therefore we have to say that assumption of metformin is harmful.

We have no serious sources stating a decrease of insulin resistance (which means better intracellular sugar absorption). We can not say seriously that metformin cures diabetes--Testosterone vs diabetes (talk) 18:49, 4 November 2009 (UTC)

TvD, we understand, but there is no point in insisting. A forum is not a RS for WP, sorry. We can add the fact that metformin sometimes reduces testorone levels, but nothing more. --Cyclopia^talk 19:39, 4 November 2009 (UTC)

Ok, and TSH too.--158.194.199.13 (talk) 20:02, 4 November 2009 (UTC)

general comments on drug sources to try to resolve above debate, getting off topic and soapboxing a bit but recurring problem

Usually the clinical trial results are the best source of information for documented effects in humans. All drugs approved for sale in the US in the past few years have their clinical trial details more or less available from Drugs@FDA ( with issues I mentioned above). These would make a good template item if the FDA would provide bookmarkable links ( I think you need to post or use cookies or something since links are generic, anyone know a soapbox on which to post this concern would help as I've tried to contact FDA already). Older drug trials results probably are available by FOIA as this seems the be rationale for even providing the facility at all. The AERS, Adverse Events Reporting System, is excellent for some exploratory original research but probably not useful for wikipedia and unlikely to be conclusive for any hypothesis. Case reports and open label tests have their uses and probably deserve mention but you could end up writing your own review article and there is the problem with introducing bias by cherry picking observations.

Causal inference has been a recurring problem in medicine and everywhere else- you would hope this would be better than economics but probably you would be wrong LOL. Confirmation bias, interpretation of data in a self-affirming light, is often used to turn associations or correlations into a causal link. I don't want to bash anyone but I happen to be aware of some recent trial failures at PFE and CEGE where it seems more people were killed that cured. The 2 from PFE related to a cholesterol transport inhibitor and an insulin related target for cancer- both of these relate to systems which contain a lot of literature with questionable interpretations. Certainly early results and expert trial design are no guarantee of success. This is probably due to time lag also as many trials start to look questionable prior to their results being announced due to new research literature coming out after the trial designs have been cast in stone ( or at least a monolith of paper).

On natural products, see some recent tirades of mine on vitamin C versus citric acid and anecdotes about fruit juice and more glib handwaiving analysis that can be summarized as "[oxidataive] damage must be bad." It turns out, ( I think the recently killed yale grad student was working on one class of molecules that do this) many molecules signal to each other with damaging oxygen species (ROS) and simply mega dosing on vitamin C can cause problems. In the meantime, while hyping "too obvious to be wrong" anti-oxidants, everyone ignores the "inert" critic acid in fruit juice but now see recent literature in this area.

My point here is that the best service to the reader and self is to try to examine the data carefully without inflicting our own desires and "too obvious to be wrong" attributions upon it. I started this witch hunt thinking it may be required to know al the lab procedures and look for obscure artifacts in methods but often you don't even need to look that deeply to find problems in various conclusions that other latch onto. fwiw. Nerdseeksblonde (talk) 11:23, 4 November 2009 (UTC)

Nerdseeksblonde (talk) 11:23, 4 November 2009 (UTC)