Talk:Metformin

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January 14, 2007 Good article nominee Listed
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To-do list for Metformin:
  • "Internationalize" lead
  • Note GI effects of extended-release formulations
  • Expand and add references to "Formulations"
  • Keep updated (e.g. TSH suppression effect being studied, pharmacogenetics)
  • Add something on use in type 1 diabetes

Contents

[edit] older entries

i think the relative importance of using metformin in the treatment of type 2 diabetes mellitus should be underlined given the results of the united kingdom prospective diabetes study (ukpds). it was the only agent that reduced cardiovascular mortality and morbidity - if i had type 2, i'd be the first in line to want metformin, ahead of sulphonylureas etc.

I totally agree. I'll see if I can find the reference. JFW | T@lk 22:08, 27 October 2005 (UTC)

i think these are the refs:

UKPDS 34 Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes. UKPDS Study Group Lancet (1998); 352: 854-865

UKPDS 33 Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. UKPDS Study Group Lancet (1998); 352: 837-853

User:62.6.139.10

Well, the first reference was already there and I've updated it further. JFW | T@lk 00:49, 30 October 2005 (UTC)

have added the word "cardiovascular" in front of complications. pernickety, but in UKPDS, sulphonylureas decreased microvascular but not macrovascular complications.

there is also an argument that metformin is no longer being the "only" drug shown to decrease CVS complications - the PROactive trial showed that pioglitazone reduced death, MI, bypass surger, strokes but not peripheral vascular disease interventions. this has led to some controversy as the trial used a composite primary endpoint (death+MI+CVA+amputation etc) which was not significantly reduced. i therefore wonder if the word "only" should be removed.

[edit] Codeine

Despite the claim of Jfdwolff (22:38, 27 October 2005 (sorted things a bit - removed the codeine stuff (does not relieve cramping))), codeine is effective for the relief of cramping caused by metformin. Codeine is indicated for diarrhea and pain relief, and as such it is immediately relevant to the common gastrointestinal side effect of metformin. This is not the place for details on the mechanism of action of codeine/morphine, but in short, the resulting morphine has a relaxing, even paralytic effect, that particularly affects the entire gastrointestinal tract (this is the cause of loss of appetite and constipation in long-term morphine users). Whether it is always effective is anther matter, hence the word "should". Caveats, such as codeine being appropriate only for short-term use, might be warranted, but in my opinion belong under [codeine]. --Anthony Duff 22:41, 4 January 2006 (UTC)

So why codeine and not loperamide, a non-centrally acting opioid constipant? JFW | T@lk 23:12, 4 January 2006 (UTC)
That's a good question to which I have found no certain answer. However, it seems "well-known" that loperamide is not effective for relieving diarrhea caused by metformin, while codeine is. Apparently, the (unknown) mechanism of induction of diarrhea caused by metformin is different than for ordinary diarrhea. A distinguishing feature of metformin-induced diarrhea is that it is associated with strong, painful intestinal cramping that occurs irrespective of what is in the colon. The initial bowel motions may be quite solid. Loperamide apparently works by making the colon insensitive to its contents, and metformin-induced diarrhea seems not to be triggered by the physical contents of the colon.
This, at least, is my best guess. With further investigation, I cannot find anything better. I freely admit that I do not know why loperamide doesn't work, if indeed it doesn't.
If metformin is causing pain, cramping and/or diarrhea, then the standard action is for the metformin dose to be reduced. However, I think this brief mention of codeine is important because it gives short-term, immediate relief to the person who is in actual pain. --Anthony Duff 23:22, 5 January 2006 (UTC)

[edit] Metformin and aspirin

Why is metformin perscribed with aspirin even though aspirin is a blood thinner and can cause bleeding? Does metformin have to be taken with another drug, such as aspirin?

Not necessarily, but diabetics are at risk for stroke and heart attack, the risk of which is reduced significantly by a low daily dose of aspirin. JFW | T@lk 16:16, 25 January 2006 (UTC)

The last line states that metformin did not receive FDA approval for type 2 DM in 1994 - a typo surely?

[edit] Avandamet

Is that Avandamet stuff really necessary on this page? It's entirely tangential to an article about metformin, and would be better put on a page of its own so as not to distract from, er, people reading about metformin! This may just be the slight beef I have with drug company names invariably appearing in the first few lines of every bleedin' drug article - but really this is irrelevant to what metformin is, and pretty uninteresting to boot.

Anyone want to argue to preserve it?

Nmg20 23:14, 3 August 2006 (UTC)

[edit] Contraindications

This section appears to give medical advice (use of "should" and recommendation to patients). Per WP:MEDMOS, could it be rewritten to be more encyclopedic language? Or would the language be weakened to be merely passively reporting on guidelines. Perhaps I'm reading it wrong? Wrt the last sentence, is "any radiographic procedure" really the guideline? Surely dental and x-rays of broken bones are OK? Colin°Talk 22:44, 12 January 2007 (UTC)

I'll see what I can do about that, although AFAIK overuse of passive voice is somewhat frowned upon. As for that last sentence, it's actually "before any radiographic procedure involving iodinated contrast"; the problem is actually the use of contrast, so no problem with plain films, dental stuff etc. Fvasconcellos 23:25, 12 January 2007 (UTC)
Perhaps my second sentence was ambiguous. I wasn't recommending passive voice, I saw that as a possible negative consequence of rephrasing. I'm not sure how best to phrase it and wondered if fixing one "problem" just introduced another. Colin°Talk 08:50, 13 January 2007 (UTC)
Ah, sorry about that. I've rephrased the sentences anyway, it does indeed look better (to me at least). Thank you for your edits BTW. Fvasconcellos 12:56, 13 January 2007 (UTC)

[edit] Suggestions from GA review

  • Try to use more patient-friendly language. I changed some, but other parts remain a little technical.
  • metformin will not induce hypoglycemia. could use a reference.

Overall, excellent. TimVickers 01:59, 14 January 2007 (UTC)

[edit] Pharmacogenetics

doi:10.1172/JCI30558 - organic cation transporter 1 polymorphisms determine metformin action. doi:10.1172/JCI32133 discuss the implications of this study. JFW | T@lk 19:35, 2 May 2007 (UTC)

Very interesting. Shame I don't have full access—this will probably warrant a mention in the future. Fvasconcellos (t·c) 12:38, 4 May 2007 (UTC)

[edit] Apprpropriate addition of important miscellaneous info

Metformin is a commonly prescribed and very important generic drug. As such, a well written drug article is necessary---especially in light of Wiki's new emphasis on a well written range of pharmacologically oriented articles. Regardless, metformin is potentially quite noteworthy due to current scrutiny of it as a possible life-extending agent. I had included a blockof text (below) previously, but it was removed from the article---probably correctly so---because it did not fit it. I am requesting that contributors consider the appropriateness of this information concerning metformin, and how it might be represented. The previously removed block of text I'm referring to follows: "Although any healthful effects, per se, other than its approved use in the treatment of diabetes, life extensionists have shown recent interest in Metformin. According to a 2003 Affymetrix gene chip study, the spectrum of human gene activation/suppression is apparently concordant between the actions of metformin and CR (caloric restriction), the latter being a recognized agent in extending life span in laboratory animals. It is unclear whether or not metformin bestows any such related benefit to humans seeking to extend healthy life span; a so-called grail of discovering a drug agent that would mimic CR has long been sought, however." --Thanks, PLK

Certainly sounds interesting. Can we get a reference for the study, please? So long as it fits wikipedia criteria (published in a respected, peer-reviewed journal), there's a place for this in the article. Nmg20 11:42, 27 May 2007 (UTC)
It does sound interesting, but I'm afraid of introducing undue weight (bear with me here) if we devote too much space to this; metformin's use as an antidiabetic must far exceed its use (use, not utility) as a "life-extension agent". Have there been any clinical implications? Perhaps a few well-placed sentences, if we can cite this properly? Fvasconcellos (t·c) 15:13, 27 May 2007 (UTC)

www.lef.org writes Is Metformin an Anti-Aging Therapy? BioMarker may have already found an anti-aging therapy with its unique technology platform. When BioMarker scientists screened several glucoregulatory agents used to treat diabetes, they found that the undisputed star of the group was metformin, which was twice as effective as the other drugs in reproducing the gene-expression effects of caloric restriction.32

Further evidence that metformin may be an authentic anti-aging therapy is that a similar drug—phenformin—was found in the late 1970s to extend life span in mice by 23%. This study by Russian researchers also demonstrated a fourfold reduction in cancer incidence in the phenformin-treated mice.33 In 2002, scientists at the National Institute on Aging presented data showing that metformin extended the life span of mice by 20%.

BioMarker is currently conducting its own study of metformin in 40 mice, seeking to determine the extent to which metformin can extend life span and reduce the incidence of age-related diseases in these animals. This study is being conducted at the University of California at Riverside under the direction of Dr. Stephen Spindler.

peer reviewed studies on metformin http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16441842&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Metformin extends the mean and maximum lifespans of female transgenic HER-2/neu mice by 8% and 13.1% in comparison with control mice. Phenformin, a close chemical relative of metformin, extends lifespan and reduces tumor incidence in C3H mice

If you find the lef.org studies online those refs will be valued

[edit] "There goes the neighborhood"

Well, "there goes the neighborhood." Since miscellany and trivia are now officially discouraged on Wikipedia, how long will it be before talk/discussion becomes overly 'mentored'? Metformin has some very interesting and potentially breakthrough features that are currently forbidden to be included in the main article. OK, I understand that the Five Pillars are an important guideline for an encyclopedia. Yet, the charm and the power of Wiki originally was similar to that of the Web itself: instantaneous action, response, as well as the immediate observance of cutting edge information. Let's try to hold onto that power, that unique aspect of Wiki that is wholly unknown to other encyclopedias. Comments---even rather impertinent seeming ones---ought to have a shot at being posted in a discussion with an ultimate goal of considering their eventual or potential worthwhile and fruitful inclusion in Wikipedia articles proper. Let’s retain what is special, and I dare say magical, about Wiki: because chasing away spontaneity will close the box whose opening was and is indeed a magic portal! --Paul Kiesow a.k.a. WikiPaull —Preceding unsigned comment added by 71.59.74.194 (talk) 01:35, 6 September 2007 (UTC)

[edit] which of the many drug product names are frequent

I found the list of product names a bit long, especially since it is in such a prominent position of the article. Made a quick search to check which ones are really in common use. Here are the hit counts as of 10/07:

2'250'000 Glucophage
53'800 Riomet
35'900 Fortamet
30'500 Glumetza
16'900 Diabex
16'400 Diaformin
154 Cidophage

According to that order I only left the hits above 30 thousand in bold and deleted product name Cidophage is almost not used.

Jakob Suckale 16:50, 31 October 2007 (UTC)

Interesting approach; I've been meaning to clean up the lead but never get around to it. Fvasconcellos (t·c) 16:55, 31 October 2007 (UTC)

[edit] LDL decrease

PMID 17638715: among a lot more interesting information, metformin therapy associated with decrease in LDL levels (and modest decrease in triglycerides). Worth mentioning? Fvasconcellos (t·c) 22:33, 6 November 2007 (UTC)

We also need to qualify the fact that heart failure is probably not a contraindication, as per a recent series of articles in the BMJ. JFW | T@lk 10:26, 7 November 2007 (UTC)
Yes, I had a read at this one. How does this sound?
Heart failure has long been considered a contraindication for metformin use, although a 2007 systematic review showed it to be the only anti-diabetic drug not associated with harm in people with heart failure.
Fvasconcellos (t·c) 15:33, 7 November 2007 (UTC)

Sounds jolly good. JFW | T@lk 21:16, 11 November 2007 (UTC)

Going in the article now :) Fvasconcellos (t·c) 22:19, 11 November 2007 (UTC)

[edit] Further evidence of TSH suppression

PMID 17992605. Fvasconcellos (t·c) 20:55, 11 November 2007 (UTC)

[edit] Use in PCOS

NEJM entire article on its use in PCOS. JFW | T@lk 08:38, 6 January 2008 (UTC)

Ooh, that's excellent. I don't suppose I could impose and ask you to flesh out the "Indications" section a bit based on this? ;) Fvasconcellos* (t·c) 14:53, 6 January 2008 (UTC)

I have read about the use of metformin in policystic ovarium sindrome and it semms that metformin increases estrogen levels or decreses testoterona levels is there any evidence that could lead to erectil disfunction or decresed sexual desire? DAZL —Preceding unsigned comment added by 201.172.237.37 (talk) 05:18, 20 March 2008 (UTC)

Try the reference desk. This page is for discussions on the article. I would imagine that in women with PCO, estrogen is lowish and testosterone is raised. Hence, treatment will improve this imbalance. Whether it happens in non-PCO diabetics is probably not documented. JFW | T@lk 08:44, 11 April 2008 (UTC)

[edit] PCOS

Metformin is commonly used in the treatment of PCOS (poly Cystic Ovarian Syndrome) also known a PCOD, PCO, or Stein Leventhral Syndrome. It help patients with condtion because it reduces insulin production , which in turn lowers the testosterone produced by the ovaries. Increased testosterone is usally the main cause of PCOS. —Preceding unsigned comment added by 76.197.15.44 (talk) 19:22, 11 May 2008 (UTC)

I understand this was (or is) an off label use. Do you have any references supporting the popularity, or not, of this use? If I just add your text to the article, it may be seen as drug company promotion. --Hroðulf (or Hrothulf) (Talk) 20:02, 11 May 2008 (UTC)
Fair point - although isn't metformin off-licence now? Anyway, the best evidence is probably PMID 12917943, which is a Cochrane database systematic review from 2002. In addition, as ever it's worth checking the PCOS article, which offers PMID 17984248, and the NEJM article mentioned in the previous comment on this page is good, too. Nmg20 (talk) 07:23, 12 May 2008 (UTC)
Hm - it would also have been worth my checking the state of the article before posting! - the Cochrane review, at least, is already in there, and the popularity question is covered, at least in the UK, by the NICE recommendation (which is also referenced). Nmg20 (talk) 07:26, 12 May 2008 (UTC)