Mostly to adult docs here, why metformin only for prediabetics at “high risk”? What other than risk of flatulence is the downside?
If someone is already exercising moderate to vigorously more than 4 hours a week, already is eating an advised diet plan, and has low body fat and no central obesity but has a strong FH and develops prediabetes due to genetic predisposition and aging, why not start metformin? Would that person be considered high risk on the basis of having prediabetes despite fitness proper diet and lack of obesity?
My mother’s abdominal troubles were caused by metformin. “Flatulence” isn’t how I’d describe it; more like needing to shit multiple times a day, constant abdominal pain, intolerance for a lot of foods (anything with “hard” fiber, such as kiwi’s seeds)…
I’m not an internist or endocrinologist. If the person was young, not on other medications, had good health apart from a sugar of 100 or 120 (I’m more used to the Canadian units), and a low creatinine under 150, I don’t think low dose metformin is a bad choice but don’t think I would start it in the ER, but as a family doctor might discuss it with the patient. Of course, your patient is likely older and not pregnant. It might depend on the level of patient concern, comorbidities and how bad the FH is.
IANAD. I have been using metformin for 12 years, but didn’t start till I had a high blood sugar (it was 8.1 mmoles/liter which, let’s see, corresponds to 146 mg/ml). I never had the slightest digestive upset. I defecate at most once a day and tens to be constipated. My blood sugar is now below 6 mm/l–108 mg/dl–and my A1C tends to be around 5.7%. Why start it earlier? I guess there might have been some value in that. I suffered peripheral neurpathy for at least 4 years before starting the metformin and that will never improve. Maybe I could have avoided that if I had started earlier.
But there was an interesting article in the Oct. Scientific American. There is some evidence that people who take metformin live longer. Right now, this is purely observational, but they are trying to design a study to test it more carefully. They want to test it on people who are not diabetic, but the observational evidence was that people with diabetes well-controlled by metformin were living longer than non-diabetics, which was not expected.
Possible mechanisms include control of inflammation. Something I observed was that in the year or two after I started it, I spontaneously lost about 20 lb, while making to effort to diet. My doctor said that that is a comon side effect and is not well understood.
Reason to consider early most spoken of is to reduce the risk of progression to diabetes, but in the bigger picture the cut-off for diabetes is pretty damn arbitrary. Prediabetes is itself associated with increased risk of the same complications (neuropathy, retinopathy, etc.) as well. There is enough reason to believe that early intervention with exercise, diet, modest weight loss will reduce those risks, and enough that metformin will also, albeit possibly not quite as well, that it is advised for prediabetics with high risk factors.
And yes it might have other positive impacts on cancer risks, dementia, and other diseases associated with aging.
Those positive outcomes occurring in lower risk diabetics has not however been proven. And clearly achieving the same ends by way of diet and exercise with modest weight loss is better.
So there are possible significant positives. And positives always should be weighed against possible negatives. I’m just not clear what those negatives are, especially for lower doses. If the worst commonly adverse impact is reversible GI issues well then dang, if it is too bad just stop it. And low dose apparently does that rarely.
The case of my op also includes the question of whether or not a non-obese and fit prediabetic (heck add in under 60) is, by the very fact that (s)he has impaired glucose regulation even in the face of that, automatically high risk.
The thing is WHAT IS YOUR BLOOD SUGAR at various times during the day? And when you first get up in the morning before eating or drinking anything?
Get a blood glucose meter and test strips. Have your doctor prescribe it and it will be covered by your insurance.
Test yourself multiple times each day for at least a month.
If your blood sugar is high, you are at risk of going blind or losing your legs! (SERIOUSLY!)
If you have had high blood sugar, have your feet checked and your eyes checked once a year.
And metformin is a good choice. With other medications you risk having too low of blood sugar which can cause death. Pretty safe with metformin. It does have a nasty side effect of causing diarrhea. (Take anti-diarrhea medicine.)
If you can regulate your blood sugar to normal levels with diet and exercise, then EXCELLENT! Best thing you could do. But do test your blood sugar to be darn sure it is OK.
Any discussing this with others offline one comment that I have gotten back is about my part two - that scenario would raise the suspicion of latent autoimmune diabetes (“LADA” or Type 1.5).
OTOH, millions of people might be labelled high risk due to a mild elevation of blood sugar. There isn’t much research I know of that suggests aggressive treatment is helpful. If the family history is bad or there are other reasons to be concerned, starting low dose metformin may be reasonable. One hears a similar argument for statins or aspirin in other populations. My own philosophy is to minimize medication, but I think the risk of harm is low and it could be stopped if side effects supervene.
What is the risk of hypoglycemia for a borderline diabetic on metformin? I was reading a book on over treatment, I believe the physician author had a bad experience prescribing an anti diabetic agent (I think metformin, but maybe a different drug) to someone who had borderline high blood glucose. The patient passed out while driving from low blood sugar and had a car accident. However, what are the real risks and how common is that?
Also the closer you get to ideal conditions, the higher the nnt, and the less benefit and one would assume the higher risk of metrics dropping too low. I know with hypertension, even with diagnosed mild stage 1 hypertension the dangers of medication could outweigh the benefits on a population wide scale. A jama report from a few years ago recommended raising the criteria for anti hypertensive therapy by about 10 mm hg.
IANOD,
I have successfully used Metformin ER for several years. According to my endrocrinologist, Metformin doesn’t lower blood sugar, it evens out the highs and lows. Passing out from low blood sugar is not a side-effect of Metformin. She also says that I should be happy that I am on Metformin-it appears to have several positive effects on the pre-diabetic body in addition to it’s on-label effects. She didn’t elaborate.
All meds have side-effects. Anyone can suffer a problem from almost any drug. But most people do well with most drugs. If you do well with it and you medically need it, stick to the plan. If not, not.
In my reading of the topic on UpToDate, I couldn’t find any specific concerns about metformin use in a low risk population. I’m left with the impression that data on the safely and effectiveness is just lacking for a population that’s not high risk. And even the data on which they base their recommendation to use metformin on high risk folks is classified as 2B.
So IMHO they’re not recommending it for low risk folks just because they can’t support it with evidence, despite the fact that it might just be a great idea.
The ACCORD study looked at intensive therapy for T2DM vs standard therapy. Intensive therapy aimed for an A1C of 6.0% or less, standard therapy aimed for an A1C of 7.0-7.9%.
However there have been debates on here before about the ACCORD study, and I think it was brought up (perhaps by OP) that the medications being used had more side effects.
Also I’m not sure if that is applicable, since OP seems to be talking about treating A1C in the 5.7% to 6.4% range, not bringing A1C in the 8-9% range down to <6%.
Hypoglycemia is extremely unlikely with metformin alone. Metformin alone will generally not be adequate to achieve the goals of intensive therapy for someone at diabetic levels.
Yes QtM that’s one part of the question: the balance between possible but unproven benefits vs extremely low risk and low cost.
The second remains if that individual would count as high risk by virtue of becoming prediabetic despite living the lifestyle promoted as desired lifestyle changes to implement to treat prediabetes, along with age under 60 and strong FH.
The LADA possibility is an added bit and makes me wonder how much of the “obesity paradox” is explained by unrecognized LADA in nonobese diabetics labelled as T2.
There’s an article in Canadian Family Physician 2009 Apr;55(4), 363-369 suggesting a NNT of 7 to stop prediabetes becoming worse using metformin. It’s by a med student and GP, not a specialist, but seems a reasonable starting point.
If you’re on it watch out for B12 deficiency. I was starting to have neurological symptoms (tingling toes and fingers and a lot of confusion). I was asking my doc about what I thought was fingernail and toenail fungus and it turns out is was symptom of B12 deficiency and I didn’t realize the other symptoms were too. Metformin is assoc with B12 deficiency. When tested I was very low. I’ve been on supplements 6 mos now and my nails have improved dramatically and I have no more neurological symptoms.
I took Metformin for years before I was diagnosed with Type II diabetes. I have PCOS and am insulin resistant. I never had low blood sugar incidents and was not warned of having them by my doctors.
When I was diagnosed I started glimiperide and added 500mg more of Metformin and I have low bloodsugar a lot now (because I exercise too much. Ha!)
Metformin is not being used on low risk patients because the general medical consensus is that the cost-benefits analysis says it shouldn’t be.
You’ve decided the risks are extremely low, but that disagrees with the assesment of the medical community. I really wish I could introduce you to my mother’s gastro. About 10% of patients on Metformin present gastrointestinal distress and the GE is sick of seeing them.
The risks aren’t deadly, but “10% of patients are in constant irregular pain, feeling like they have diarrhea* while actually presenting constipation” combined with “60% of my suspected-IBS patients turn out to be suffering from Metformin side effects” is not what a GE calls “extremely low risk”.
I don’t know how to say rayadas in English. It’s when you get this sharp abdominal pain, like someone is taking knives to your belly, most commonly as part of a bad case of diarrhea or of having your period.
Wesley some of the details about ACCORD and other trails here. I think you’ll find it interesting. Of note is that “standard therapy” was of course more often metformin alone than “intensive therapy” was. The context includes the previous UK Prospective Diabetes Study (UKPDS) metformin alone “achieved a mean A1C level of 7.4% with 8% in a control group, associated with a significant 39% CVD reduction” while “metformin with a sulfonylurea was associated with 96, 60, and 9% increases in diabetes-related and all-cause mortality and in myocardial infarction.”
The benefit of metformin may not be directly tied to its glucose control impact alone and much tighter control achieved with certain other medications added may in fact be of harm. If I was a diabetic I’d be very hesitant to be on that metformin with a sulfonylurea combo for example!
Moreover ACCORD in combination with other large trials does inform some about the question being asked:
Good point on the B12 issue. The GI one though … to me is a meh one. If it occurs in the context of a borderline indication stop the med and it goes away.
And the answer to the question of why is something the current medical consensus is not because it is the medical consensus.