Anyone been on metformin?

Hi all- Metformin was recommended to me recently as adjunct to treatment I am already on (Avastin and Etopiside). I am 2 years into treatment and have Stage 4 OC. I'm wondering if anyone has had success using this drug ? Any negative consequences. My alternative doctor thinks I should definitely take it. I haven't brought it it up yet to my Kaiser doctor yet but I think he'll say it hasn't been approved yet so he wouldn't recommend. Thanks for whatever info you can give me. I really appreciate you all!

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I have been on a low doses of metformin...500mg daily....I split the pill so I get 250 mg with breakfast and 250 mg with dinner. I started Oct 1. So far no bad side effects. It makes me less hungry which is awesome for me since I never have trouble with my appetite. My blood work has stayed normal. No one will be able to determine how effective Metformin is with OVCA until a bunch of us go out a long time.

Now the scoop for me is this. My onc did not support Metformin use because it hasn't been proven. However, my primary care doc said that women with ovca are in a tough place and she would support at least a low dosage just in case! So she is the one who monitored me at first. I've checked with many naturopaths. All support going on Metformin...just in case. I asked about Berberine Balance which is a product ND's use with diabetics and the ND that used it the most still told me to go on Metformin because its cheap, been around for many years, effective and they know about side effects.

Metformin does more than regulate blood sugar. It's supposed to work with halting cancers because it affects the MTOR pathways. That is the reason its supposed to work. Originally I think it was conceived back in the 50's it was tested as a diet pill. Works for me!

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Thanks Rabbitgal for your usual cogent succinct factual review of a treatment....you're so darn smart! It's been suggested to me too, and thanks for giving first-hand information.

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IBI,

Thanks...nose twitch, nose twitch!

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The major side effect for most people is diarrhea and gas. For most that gets better over time, but for some here it was intolerable and they had to stop.

I tried it for a few months, and my CA125 which had been stable for quite a while, shot up. My onc had agreed with this "experiment" but once my CA125 took off he also agreed with my suggestion that I stop. I'm now back on chemo. Of course there is no way of knowing whether the rise is connected to the metformin use. For all I know, maybe it would have been much worse without the metformin.

In looking around the literature I found a preliminary report of some results from one of the many clinical trials that are underway. It concluded that there were two groups of patients in terms of their response to metformin. The first group, whose tumor markers improved with metformin use, tended to be either diabetic or pre-diabetic. There was a high frequency of insulin resistance, and also of obesity. The second group, which tended not to have those conditions, actually got a little worse on metformin. I am not diabetic, pre diabetic or obese. This was a small preliminary study and unfortunately we really have to wait til the end of this year to get more definitive answers from clinical trials. But it did give me a heads-up that this could possibly not be entirely benign for everyone.

So as far as metformin is concerned I decided to wait for more results rather than continue that line of experimentation on myself. If I had insulin resistance though, I would be much more likely to take it.

Just the results of one person's short clinical trial of one, lacking any statistical validity whatsoever.

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I just started metformin 500mg once a day and will increase to 500mg twice a day in 2 weeks. Too early to probably experience any side effects. (My family doctor recommended the extended release time to decrease the possibilty of side effects; am so lucky to have doctors that work together) I have run out of chemos to try -have had 14 different types of chemo continuously in the past 8.5 years. Started on tamoxefin 20 mg 2 times a day about a month ago and my ca125 hit 12,200. I am fortunate to have a gyn/onc who is willing to try some non-conventional drugs. Best wishes to you.

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Jurate...thanks so much for your insight on this. I aske my gyn-onc for it and got a big, fat NO. I then asked my primary care doc for it and got a second big, fat NO. I was feeling frustrated....metformin is a relatively benign drug (comparatively speaking) and really wanted to try it. I too have a normal BMI and am not pre-diabetic. Your response helped me see another side of things.

-Janet

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I asked my mothers oncologist about putting her on it in November when her ca125 began to rise. He agreed. Her ca125 at that point was around 69. Checked back in a month, ca125 was 59. We were very happy. However, she went back Friday and had blood work done. We found out today her ca125 was 82 :( So we are going to hang tight and visit a dr that practices Chinese medicine and herbal remedies Friday. Give those a month and check back. I assume she will continue on the metformin this month.

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Hi...I started on it in July 2012, with 500 mg, then 1000, now 2000 mg. It has stabilized my CA-125 and kept it from shooting up. In 2011, my CA-125 went from normal to 400 in 7 months off chemo. This time, it is 200 in 7 months off chemo. I use a few supplements, but am convinced that Metformin is the major factor behind the slower rise this time. I am a Type- 1 Diabetic who takes insulin, and also BRCA-1 positive. My CA-125 has been rising about 30 points a months for the past 3 months, which is not ideal, but in 5 years with this disease, I've never had such a slow rise. (Been on 4 traditional chemo drugs and a PARP). No real problems building up to 2000 mg/ day except for the first week.. some digestive issues. I'm convinced it could be a good drug to add to our arsenal. In my case, it is certainly slowing the disease down. It may work better on cancer for insulin-dependent diabetics like me. Am not sure on that one.Read that somewhere. However, there is research out there indicating it also blocks cancer cell growth from more than one molecular growth pathway, which I understand is always a good thing! Best to you with trying it... it doesn't seem to do long-term damage to the liver or kidneys that I have read. I have a friend who's taken it for his diabetes for over 10 years. He doesn't appear to have any residual damage from it. My vote would be go for it! Please let us know if you do, and if it helps. I really hope it does!!

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I have it prescribed via naturaupath and primary care doc. Take just 500 mg once/day. No real side effects except less hungry. I was going to increase it to twice/day but decided to hold for now as I wait for first ct scan results in 7 months (eek!) really, really hoping to finally show no new tumors after 18 month of different chemos. I am cautioned by Jurates perspective on metformin - it may be a low side effect drug but I am in the non diabetic category and don't need anything to support my cancer!

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Wow- great feedback. I feel more confident in going ahead now- but also with some watchfulness since I am not diabetic or prediabetic. Thank you all!!

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I'm sorry if I'm being too blunt here, but I would NOT go ahead with it without consulting your Kaiser doctor, if that is who is giving you your chemotherapy. It these drugs are strong enough to work, they are also strong enough to have problems and interactions with other drugs.

It isn't always that something good just hasn't been approved, sometimes its too soon to know if it makes things worse.

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3Bean... not too blunt. There are always a number of factors to consider. For me, it seems to be working. It may not for someone else, like Jurate. There is some level of risk in anything we do or try, and it is always good to go ahead in an informed way, if we decide to go ahead, as you said.Drug iInteractions are very important to consider. I may need to take more care about my own attitude.. after 5 years of this disease, and trying many things to slow it down and fight it, I have a pretty die-hard attitude and not too much scares me, in the "taking risks" department. Sorry if I was too quick to be so positive on this topic!

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Thanks for raising this and for all your comments. I've been exploring Metformin since a study came out from Mayo clinic in early December which compared diabetics with ovarian cancer who took metformin with those who did not. It was retrospective, but found those on metformin had a 50% increase in survival time. I looked it up and asked my gyn oncologist about it and he said that there were no clinical trials, in part because the drug company has no incentives because metformin is so cheap. He also said that he could not prescribe it "because the powers-to-be would be all over him. (Interesting, he's in a major teaching hospital, chief of department). He said he expected we'd hear more about metformin in the future. I have followed through and a second source, a researcher in ovca confirmed the problem with getting funding. However, a clinical trial is starting in Michigan for newly diagnosed.
Turns out I might never get into a clinical trial as I had a stage one melanoma 23 months before ovca which makes me ineligible to any clinical trials unless it's 5 years out. That's another issue.
I raised the issue with my primary care physician last week who said she would check on it. Another medical friend has suggested asking my oncologist to work with an endocrinologist. In any case, I would not do anything without letting him know.
I was interested in Jurate's comments about the literature indicating that it worked for people with diabetes and prediabetes and may be counterindicated for others. Can you let us know your sources. I'd like to share them with my pcp.
This is one of many occasions when I miss Greg. His comments were always so helpful.

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This article from Medscape describes the study on Metformin that was released in December. BTW, I'd suggest subscribing to Medscape for info on research. Subscription is free. It's for medical and related professionals, but I find it readable.

Metformin Boosts Survival in Ovarian Cancer

Roxanne Nelson
Dec 06, 2012

A common medication used to treat diabetes could prolong survival in patients with ovarian cancer, according to a new study.

Although the findings only suggest a correlation between metformin and improved outcome (causation could not be assessed), they indicate that metformin intake independently predicts better survival in patients with ovarian cancer, the study authors report.

The study, published online December 3 in Cancer, found that 5-year disease-specific survival was significantly better for patients with ovarian cancer who took metformin than for those who did not (67% vs 47%; P = .007).

The authors note that the results of this retrospective case–control study support further clinical trials of metformin in ovarian cancer. "We believe that studying metformin as an adjunct therapy for patients with ovarian cancer would be a great starting point," said lead author Viji Shridhar, PhD, professor of laboratory medicine/pathology at the Mayo Clinic in Rochester, Minnesota.

"The preventive value may also be tested, but will be more time consuming, since this would involve a long follow-up period to assess the benefits," she told Medscape Medical News.

At this moment, we do not recommend using metformin for ovarian cancer. Dr. Viji Shridhar


These are early data and risk/benefit has not been assessed. Dr. Shridhar pointed out that although metformin is generally safe, it does have some adverse effects, such as nausea/vomiting, cramping, abdominal pain, and diarrhea. "At this moment, we do not recommend using metformin for ovarian cancer," she said. "The data are based on a small number of patients and we need large-scale randomized clinical trials," she explained.

"A positive outcome from large-scale studies that show metformin to be effective will be the starting point to make a practice change," Dr. Shridhar added, "but not at present, based on these data alone."

Previous Data Support Benefits

A number of studies have evaluated the use of metformin in the management and prevention of a number of cancer types, including prostate cancer, colorectal cancer, pancreatic cancer, and nonsmall-cell lung cancer, as previously reported by Medscape Medical News.

In a study of ovarian cancer, published earlier this year (Obstet Gynecol. 2012;119:61-67), 5-year progression-free survival rates were 51% in patients with diabetes who used metformin and 8% in those who did not; in patients without diabetes who did not use metformin, the rate was 23% (P = .03). Overall survival rates at 5 years were 63% in patients with diabetes who used metformin and 23% in those who did not; in patients without diabetes who did not use metformin, the rate was 37% (P = .03).

Study Details

Dr. Shridhar and colleagues studied patients with ovarian cancer being treated at the Mayo Clinic who had received a prescription for metformin from 1995 to 2010.

In the preliminary analysis of women with ovarian cancer, 72 women treated with metformin (cases) were compared with 143 who were not (controls).

In the definitive analysis of women with epithelial ovarian cancer (EOC), 61 women treated with metformin (cases) were compared with 178 who were not (controls). In the EOC cohort, patients in the 2 groups were matched for age at diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, and surgical cytoreduction status (optimal vs suboptimal).

In the ovarian cancer cohort, median disease-specific survival was 5.5 years (95% confidence interval [CI], 4.1 - 7.5 years). For cases, median survival was not reached (log-rank P = .002); for controls, median survival was 4.1 years.

The 5-year survival rate was higher for cases than for controls (73% vs 44%; log-rank P = .002). After adjustment for variables such as age, year of diagnosis, body mass index, disease stage, histology, and chemotherapy, only grade (hazard ratio [HR], 8.6) and use of metformin (HR, 2.7) remained independent predictors of survival.

In the EOC cohort, the mean duration of follow-up for cases was 3.7 years (median, 3.4 years) and for controls was 4.3 years (median, 3.3 years). Median recurrence-free survival was higher for cases than for controls (32 vs 22 months; P = .04). The 5-year disease-free survival rate for the entire cohort was 52%. After adjustment for variables such as grade, histology, and chemotherapy, metformin remained an independent predictor of survival.

The study was supported in part by grants from the Fred C. and Katherine B. Andersen Foundation and National Institutes of Health grants. The researchers have disclosed no relevant financial relationships.

Cancer. Published online December 3, 2012. Abstract


Medscape Medical News © 2012 WebMD, LLC

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I've been on Metformin for Over 5 years a diabetic. I'm currently maxed out at 2000 mg daily. I was diagnosed with OVCA 3 years ago (3B) and have been NED since. I can't really say whether being on Metformin has been a help or not, this is just my story.

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BartersIsland, there are clinical trials. I found some on clinicaltrials.gov. The combination search Metformin + Cancer brings up 146 hits, (most of them not on ovarian cancer).

Here is the reference for the two populations of responders to metformin:
http://www.ncbi.nlm.nih.gov/pubmed/22564993
I didn't mention that this study is on breast cancer. Some of the metformin trials are on breast cancer or other cancers.

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BartersIsland, someone should tell your oncologist that the NIH does fund clinical trials on cheap nonpatented drugs. It's an important use of our tax dollars. I don't think he's doing the public a service by telling them that only expensive drugs go to trials.

And he can prescribe it to you if he sees fit. There are many people here whose doctors have prescribed it, including some very highly regarded doctors. Metformin is an old drug with an excellent safety record.

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from a CNN news story last April:

"Pharmaceutical companies that spend billions to develop patented -- and expensive -- cancer drugs have little incentive to fund or conduct studies on generics like metformin.

As a result, metformin researchers have struggled to scrape together the money needed for clinical trials, which can run into the millions. Many of the ongoing metformin studies around the world are "being done on a shoestring budget, in a sort of informal way," Pollak says.
.....Governments and nonprofit organizations have begun to fill the money gap. The National Cancer Institute (NCI), for instance, is funding dozens of clinical trials that are currently under way or recruiting patients.

One of these studies, led by Goodwin, is exploring the effect of metformin on breast-cancer recurrence in 3,582 women. The other major funders for the trial are the Canadian Cancer Society and Apotex, a generic drug maker that has agreed to provide free metformin and placebo pills.

A recent shift in thinking at the National Institutes of Health (NIH), which includes the NCI, seems to be working in metformin's favor.

In 2011, NIH director Francis Collins, M.D., said that "drug rescue and repurposing" would be a major focus of the agency, with the goal of investigating new uses for already approved or abandoned drugs.

A few days later, the agency's associate director for science policy, Amy Patterson, M.D., mentioned metformin as a prime example of this approach. Two-thirds of the NCI-funded clinical trials of metformin now under way were initiated in 2011 or later."

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