Diabetes drug Metformin shows benefits on aging and a number of diverse diseases.
Researchers at McMaster University have unlocked one of the secrets behind the many benefits of metformin.
One of the most widely used medications in the world, metformin is commonly prescribed for Type 2 diabetes. However, in addition to its effects on lowering blood sugar, in preclinical models, metformin shows benefits on aging and a number of diverse diseases such as cognitive disorders, cancer, and cardiovascular disease.
One question researchers have been asking is how this is being achieved.
A multi-year study led by a collaboration of McMaster’s basic science and clinical researchers has found that metformin induces the expression and secretion of a protein called growth differentiating factor 15, or GDF15.
The results were published today (December 9, 2019) in Nature Metabolism.
“Studies over the past two decades have shown that metformin does more than lower glucose, but we haven’t understood why,” said Gregory Steinberg, senior author, and professor of medicine at McMaster. He is also co-director of the Center for Metabolism, Obesity and Diabetes Research at McMaster.
“We went into this study with the idea that metformin might communicate with other tissues in the body by causing the secretion of a protein from the liver. We were totally surprised when we found out that metformin caused the secretion of GDF15, a protein which is known to suppress appetite.”
The study team took that knowledge and applied it to mice to better understand the science behind the outcome. Scientists deleted the gene that makes GDF15 in mice, then treated them with metformin. The results showed that mice without GDF15 did not eat less or lose weight, despite being administered metformin, establishing GDF15 as the connection between metformin and weight loss.
The researchers say the findings open a number of avenues of research. There are currently over 1,500 registered clinical trials to test the effects of metformin in aging and different diseases.
“The possibility that GDF15 has a role in multiple beneficial effects of metformin treatment on aging or diseases like cancer needs to be studied,” Steinberg said.
Reference: “Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss” by Emily A. Day, Rebecca J. Ford, Brennan K. Smith, Pedrum Mohammadi-Shemirani, Marisa R. Morrow, Robert M. Gutgesell, Rachel Lu, Amogelang R. Raphenya, Mostafa Kabiri, Andrew G. McArthur, Natalia McInnes, Sibylle Hess, Guillaume Paré, Hertzel C. Gerstein and Gregory R. Steinberg, 9 December 2019, Nature Metabolism.
DOI: 10.1038/s42255-019-0146-4
The study was funded by the Canadian Institutes of Health Research (CIHR) and Diabetes Canada.
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37 Comments
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I was put on Metformin for prediabetes. It was probably the worst 4 months of my life. I had diarrhea and abdominal pain the entire time I was taking this drug. The reason you loose weight is you poop yourself thin because you’re chained to the toilet. Horrible drug
Why would someone with such an un-scientific view and who draws conclusions based on the anecdotal evidence of a single patient be reading SciTechDaily?
George, she is correct that metformin quite often causes gastrointestinal distress, which is sometimes intolerable. However, she is wrong about this being the reason people who continue to take the drug lose weight.
Scientific proof is in the pot.
When I was put on metformin 3 days later I felt like I was dieing I was taking to hospital by ambulance to find out I was allergic to it
I’ve been taking two grams per day of metformin hydrochloride for around 20 years. I had some indigestion for the first few days, but no problems since.
It’s a wonderful drug, easy to obtain, and inexpensive. It is extending my life as I write this.
I am right there with Deb. Terrible abdominal pain and diarrhea. I get terrible nausea and feel miserable.
I originally took 850mg Metformin for pre-diabetes and had similar reaction. Dr changed dose to 500mg and all has been fine. No nasty physical issues. My weight has certainly maintained, not increased, and I am not on a rigid diet either, just trying to eat good balanced meals.
I also agree with Deb, a horrible drug! I was on it for 2 months while I was in the hospital a nd they expected me to stay on it…nope, if I wanted to have to run to the bathroom every few minutes of my life…id rather just say heck with it and take laxatives. Horrible, horrible way to lose weight!
I have taken Metformin for 2.5 years. Eating before taking Metformin helps with the initial problems with loose stools. After a month or so, the cramping and loose stools subsided, with only occasional problems.
Having IBS for my entire life, I can say Metformin had an initial effect with loose stools. Again eating before taking Metformin, makes the difference in not having the cramps and loose stools.
With regard to weight loss, we must change our lifestyles and eat and drink responsibly. Having said that, counting carbs, tracking daily glucose levels, drinking alcohol less or not at all, tracking amounts of calories, protein and fat intake, makes life better and easier.
I keep a daily log with EXCEL and have an A1C of 5.3 and glucose less than 120. These are down from A1C 9.6 and Glucose over 210.
BTW I lost 30 pounds within a year and a half. All my labs are in the ballpark and I take all my medications regularly.
I’m interested in exploring additional medications that could complement metformin in my weight loss journey. I recently used Zepbound for eight weeks and experienced significant success, losing 12 pounds in that time. Unfortunately, I had to stop due to insurance challenges, and it left me searching for alternatives.
Having struggled with weight loss for years through various diets and oral medications, I’m now more motivated than ever to find effective solutions, especially considering my family history of heart disease. I believe being proactive about my health is essential.
If anyone has suggestions for combinations of weight loss medications that work well with metformin, I would greatly appreciate your insights or advice. Thank you!
Thousands of people with type 2 diabetes take this drug. I doubt all them suffer as described. Even the Harvard biologist who descovered reservatrol takes it (Metformin) for anti-aging.
I read a lot about Metformin they do not know how it works for sure. Some says in the Stomac, some say in the brain.
My husband was put on 2 grams a day.
2 ×500 mg with a main meal.
He started diarrhoea and stomac issues , but the doctor said will subside , the kidney pain.On scan there wad nothing wrong with kidneys.
Doctors said to take it and added gliclazide to it as well. he did not loose weight and put another 5 kg on.
It is annoying with all the side effects but he has no choice.
Want metaphorum for weight loss my doctor won’t give I have afib they said cart ivascular you can get put on 20 pounds.
I agree 100% with Deb. Metformin made me horribly sick. Stomach issues, diarrhea. My Doc at the time told me it would go away and it never did so I went off of it. It was given to me when I was pre-diabetic. I was able to get healthy on my own. It never helped me loose weight either but my new diet helped me at that time.
I have been on Metformin for 6 months 500mgx2/day – 1st 30 days there was some occasional discomfort. Since then, no issues at all. Not sure it’s had any impact on glucose levels though. Continuous Glucose Monitor (libre) CGM is what’s made the real difference. Direct feedback on cause and effect is a wonderful motivator. Highly recommend.
I was also prescribed Metformin for pre-diabetes. I tried taking it on three separate occasions over a three-year period, each time for 2-4 months, and it was absolute hell: severe abdominal pain with constant diarrhea, nausea and vomiting. I was really ill and barely able to function for the entire time I took Metformin and for up to two weeks afterwards. I kept on taking the stuff hoping it would get better but it just got progressively worse. Right now I am trying to manage without any medication for the pre-diabetes, just diet and exercise.
All medications affect different people differently, and while I do realize that this medication obviously works well for some people and I am happy for them, for some patients it just isn’t the answer.
I’m a type 2 diabetioc and have been on the max dose (2000 units a day for several years with no ill effects whatsoever. Maybe I’m just lucky.
I DO HAVE TO WONDER WHETHER “INDUCING THE EXPRESSION AND SECRETION OF GDF15” IS SOMETHING POSITIVE. IT APPEARS THAT THE ROLE OF GDF15 IN CANCER IS UNCLEAR:
https://jeccr.biomedcentral.com/articles/10.1186/s13046-018-0744-0
FOR THOSE WHO HAVE SUFFERED THE INDIGNITIES OF METFORMIN, HAVE ANY OF YOU LOOKED INTO BERBERINE AS AN ALTERNATIVE? (YOU HAVE TO TAKE IT WITH CINNAMON TO ENHANCE ITS BIO-AVAILABILITY.)
ANY SCIENTISTS IN THE CROWD WHO COULD SHED SOME LIGHT ON GDF15 OR BERBERINE?
There’s an extended release version of metformin, if you have stomach issues. It works for me.
The people having allot of trouble were you taking 1000 mg or 500mg. when I took 1000mg I had trouble but with 500mg I eat what ever I want and my blood sugar stays between 130 and 230. I am not able to exercise and my weight stays the same. have not gained any since starting this medicine. knock on wood
“I have diabetes, take metformin, can’t exercise, and eat whatever I want.” A puzzle: What’s wrong with this picture? Which of the 4 phrases doesn’t belong?
I too had diarrhea issues when I told the diabetic nurse she told me she was putting me on extended release metformin no issues since.
One side effect in a individual should not be the reason to debunk the medicine. Probably prompted by a corporate that sells expensive alternatives to metformin.
What bs! Test people not rats and then ask them what’s going on.. it should be a nonissue but pharmaceuticals make so much money from all the over engineered garbage we’ll all die cuz of some cancer causing side effect.. I hope some kid in a 3d world country figures it out and spams the world with the cure.
I take Metformin XR 1000mg twice daily. The comments that controlling your appetite is key, because, I can eat right past it. An excersise in self discipline. Yes, side effects are true. Still, my eyesight has improved and I maintain my BMI. I like to eat. The master of my own results. Don’t give up and trust your doctors.
I have been taking XR 1000MG twice daily since last 5 years, 3 days a week workout able to maintain 7 and below A1C, in last 16 years only once A1c shoot-up to 8. Without workout its impossible to control, keep sweating physical health take precedence over financial. Posting A1c results over years, hope it may help.
2014 -6.4.
2015 -6.8
2016 -6.8
2016 -7.6
2017 -7.3
2017 -8.1 — able to lower with workout without adding any med
2017 -7.8
2017 -6.9
Want metaphorum for weight loss my doctor won’t give I have afib they said cart ivascular you can get put on 20 pounds.
Diabetic type 2. I also have ulcerative colitis. I take metformin 500 my ER twice daily. B/S are 130-170 in am, Evening 140. I have been in remission with colitis for about 8 months, When started on metformin with in 3 months I’m suffering with my colitis. Now you tell me it may be from the metformin? This kinda stuff drives me nuts.
I will say I have lost about 8 lbs. I am trying to exercise an portion control my diet.
I will continue with metformin to see if my a1c drops.
Awful stomach ache and gas with running to the bathroom and crapping the bed. Someone needs to research that.
Deb Mummy he same thing happened to me. I broke my tablet in half and took half in the morning with breakfast.and the other half at night after dinner. Diarrhoea and all other side effects stopped immediately and I’ve been fine ever since. Been on it for years now.
nice article thank you, there is also senna tea if you have ever heard of it, it help a lot in losing weight.
I just added Metformin XR 500 MG/2x to my change in food and daily cardio/weight training. I haven’t been this sick in my entire life. I teach and have barely made it to the RR twice this week with diarrhea. It’s Tuesday. This morning I vomited on my commute to work. I’ve had more than 5 painful bowel movements each day. I’ve been very careful with my meals and medication schedule. I’m not sure I can take this for “several weeks” as recommended for GI issues to improve. I’m so glad this works for others, but please don’t suggest someone is being negative to slight the medication. Super unkind.
My doc prescribed it for weigh loss. Im 52 but always been about 20-30 lbs overweight. I take 1000mg. I have been hospitalized for terrible IBS in the past and not other diagnosis other than IBS. I was always released and told IBS can be like a migraine of the stomach and gastric twisting and gas can derive from foods, nervousness and stress. I lost 67lbs on my own but gained 30 back so I struggle. I have been taking metformin for two weeks. I was worried because of my past tummy issues. I had painless diarreah for a few days and now no issues. I weigh next week. I feel a little lighter but we shall see. I work out 4-5 days a week teaching Zumba.
thanks for this