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).

The first sources in the article have not scientific value and they are not scientific articles, they are just pubblicity--158.194.199.13 (talk) 17:53, 29 October 2009 (UTC)