Metformin, the diabetes drug developed from French lilac

[AussieNeil]

Metformin is the most widely used drug to treat type 2 diabetes globally.

More snippets from the article by Merlin Thomas, Adjunct Professor of Preventive Medicine, Baker IDI Heart & Diabetes Institute, which I hope will be at least of interest for those with a diabetes II co-morbidity with their CLL, : theconversation.com/weekly-...

'Metformin was originally developed from natural compounds found in the plant Galega officinalis, known as French lilac or goat’s rue.

Synthetic biguanides were developed in the 1920s in Germany, but their use was limited due to side effects. During the 1940s, however, French physician Jean Sterne examined a new biguanide called dimethylbiguanide or metformin. At the time, it was being studied for the treatment of influenza, but Sterne recognised it had glucose-lowering properties. He proposed calling it glucophage, meaning glucose eater, a name with which it is still commercially associated today.

Metformin has been used to treat diabetes since the late 1950s. It is now on the World Health Organisation’s List of Essential Medicines needed for a basic health care system.

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Metformin is associated with a rare but life-threatening condition known as lactic acidosis, where the body builds up too much lactic acid. This can be caused by factors such as heart, liver or kidney failure. There is still controversy over whether metformin is the cause of lactic acidosis or whether it exacerbates the condition.

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Metformin competes for clearance by the kidneys with drugs including digoxin (for heart rhythm problems) trimethoprim and vancomycin (antibiotics), ranitidine and cimetidine (for heartburn), nifedipine and furosemide (for blood pressure) which all have the potential to modestly increase metformin levels.

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Some clinical trials have shown that metformin is at least as effective as diet and exercise for preventing diabetes in those at high risk of developing it.'

Neil

Photo: Pink fairy orchids recently found in the scrub. These native orchids have had an exceptional year thanks to our wetter than average winter and spring.

[MelioraDay]

The University of Michigan has a pilot study looking at metformin therapy in CLL. The purpose of the study on clinicaltrials.gov is as follows:

Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication. More recently metformin has been shown to act against carcinomas by two mechanisms: 1) an indirect, insulin‐dependent mechanism which sensitizes tissues to insulin, inhibits hepatic gluconeogenesis, and stimulates uptake of glucose in muscle, thereby reducing fasting blood glucose and circulating levels of insulin, lowering the pro survival activity of the insulin/INSR axis, and 2) a direct, insulin‐independent mechanism which activates the AMP‐activated protein kinase (AMPK) pathway and leads to inhibition of the mTOR pathway. Given the investigators preliminary published data on insulin and mTOR inhibition[1] metformin is an attractive candidate for a pilot clinical trial in CLL patients.

[AussieNeil Partner Administrator in reply to MelioraDay]

That's very interesting to know, thanks!

Here's the reference for those wishing to investigate this clinical trial: clinicaltrials.gov/ct2/show...

[Newdawn Administrator]

Metformin is generally well tolerated but has the unfortunate side effect of gastric upset in many patients (including myself). That's how it's gained its affectionate name Metfartin in the diabetic communities!

I abandoned Metformin early after diagnosis because it simply made me feel wretched. I do however believe my doctor had started me on too higher a dosage and slow release is less brutal on the stomach.

I was aware of studies relating to Metformin and CLL and I know of a very well medically informed CLL'er from the forum who takes it even though she's not diabetic. There's been a fair bit of media coverage too on its possible link with increased longevity.

But for now I'd rather try to control my diabetes with diet and exercise.

Newdawn

[Justasheet1 in reply to Newdawn]

Metfartin! 😂😂😂

Great stuff Newdawn!

Jeff

[JoanneIO]

Thanks for posting about metformin.

If you think metformin will help you, then start with a ketogenic diet, supplement with exogenous ketones, and/or MCT oil (C8). They all work on the same mTOR pathways increasing insulin sensitivity, lowering blood glucose and switching the body/brains primary energy source to ketones.)

Most people turning to the ketogenic diet are metabolic syndrome, diabetes or weight loss.

Look at the research by Dominic D'Agostino at South Florida (his focus is metabolic - aggressive cancers, brain & metastatic without good standard of care and deep water seizures for the Navy Seals.)

And Thomas Seyfried at Boston and some in Germany. Seyfried has a cancer protocol that's very strict. His research is only with mice. I'm not that strict.

I couldn't do green tea extract. I have done turmeric supplement for years. And am slowly increasing the amount per day.

I considered keto a 'Pluto' shot with CLL, because our diagnosis isn't confirmed with a PET scan. (a radioactive glucose is used to light up the cancer tumors). But my thinking is starting to change. Aggressive cancers are just more demanding and voracious for glucose than our slower CLL.

I started with the diet in January. It took longer for me than 'regular' folks to adapt. But slowly my fatigue is nearly back to pre-diagnosis levels. Not 100% back. But definitely a LOT better. Lost 10 pounds. Hubby lost 31 pounds. Switching from being a carb addict to fat adapted is a mental & physical adjustment. But now we LOVE eating this way.

FYI, if you get HANGRY. You are a carb addict.

We supplement with MCT oil (1-2 Tablespoons drizzled on food). Will switch to C8 when our supply of MCT is gone.

Haven't needed to add the exogenous ketone salts or esters.

---

Dx December 2015

13q-

My ALC is oscillating around 15. On watch & wait, 6 month checkups with oncologist

[Newdawn Administrator in reply to JoanneIO]

The ketogenic diet is very persuasive and I've found that the diabetics who do best on the sites are following a keto or similar diet. Despite the warnings, they also seem to bring their cholesterol levels down.

Many medics and dietitians struggle to adapt and still demonise fat when it's become very obvious to many that it's the carbs causing the major issues. I haven't adopted the diet in the purist sense but am doing what I can to stay as faithful to it as possible.

I have no idea what exogenous ketone salts or esters are however.

Newdawn

[JoanneIO in reply to Newdawn]

Fortunately my GP is knowledgeable & supportive.

Hope you find a medical team that supports you.

The diabetics I know have reversed all markers & are off meds. Some struggled to control it the old standard way.

Exogenous ketones are used by elite athletes & body builders. Parents are also using it for their epileptic kids to reduce seizures.

Try this site: eatingacademy.com/personal/...

Google Search on BHB ester or BHB salt. Or ketone esters

[Newdawn Administrator in reply to JoanneIO]

Thanks Joanne, I'll take a look at those links.

I'd written a full response but have had to delete it when I realised the thread isn't restricted to the community and details could have identified me.

Bottom line is type 2 diabetic care here is sketchy and I've adopted a DIY response!

Regards,

Newdawn

[pkpayne]

After I had most of my pancreas removed due to a tumor, the surgeon at MDA told me that I would likely end up diabetic. So my PCP has monitored my blood every 3 months since then. After a while my a1c started to climb and I was started on Metformin - 500 mg - once a day. That worked for a few years and then it started to climb again and my dosage was increased to 500 mg twice a day. I haven't had any noticeable side effects. My PCP tells me that I'm not diabetic - my BMI is 20. I am W&W and diagnosed 4/2016. Thank you for sharing.

[aremmick]

My natural doc wants we to start the ketogenic Diet and metformin. I'm willing to try anything my counts more then doubled last checkup. Need advise -- please help!

[Newdawn Administrator in reply to aremmick]

Hi aremmick,

When you say your counts more than doubled last checkup, are you referring to your lymphocyte counts or blood glucose?

Newdawn

[aremmick]

Lymphocytes

[Newdawn Administrator in reply to aremmick]

I’m unsure why your GP is recommending a ketogenic diet and Metformin for CLL or high lymphocytes aremmick. Are you diabetic or very overweight?

I got my blood glucose levels out of diabetic range and reduced my weight but it had no impact on my lymphocyte level which marched on regardless.

Best wishes,

Newdawn

[AussieNeil Partner Administrator in reply to aremmick]

It is very important to gain the appropriate perspective here. Over what period did your lymphocyte count more than double and what were your counts? Lymphocyte counts can more than double and be of no particular concern provided they are low enough to start with. CLL specialists don't look at doubling time until the lymphocyte count exceeds 30, simply because below that value they can bounce up and down considerably without concern. We have members with counts above 200 who are still in watch and wait and are otherwise well. Even if counts more than double within 6 months (one of the trigger points for beginning to consider starting treatment), a CLL specialist is likely to observe more closely (more frequently blood tests) and hold off starting treatment if the patient is otherwise well. The highest lymphocyte count I've heard of in a CLL patient is 1,400 (or 1,400,000 in the USA).

Non CLL specialists can get quite alarmed at high lymphocyte counts, because in other leukaemia and lymphomas, high counts can cause blood circulation problems, as the lymphocyte cells are large. The small lymphocyte cell size in CLL/SLL means that for us, thankfully this is rarely a problem.

Neil

[aremmick]

My lymphocytes could went free m 22 to 51 over a 6 month period. I'm not overweight and I'm not a diabetic.

[AussieNeil Partner Administrator in reply to aremmick]

Your doctor may have read this paper: ncbi.nlm.nih.gov/pubmed/262...

This is fairly new research and it may be that metformin could work for some of us if we have the appropriate CLL genetics, CLL being such a heterogeneous disease. Otherwise I would have thought that the effect of metformin would have been more well known.

There is also a clinical trial at the University of Michigan Cancer Center: clinicaltrials.gov/ct2/show...

Keep us informed on how you go,

Neil

[Newdawn Administrator in reply to AussieNeil]

Well done to aremmick’s doctor if he’s recommending Metformin based on fairly cutting edge research like this. Seems strange to add a ketogenic diet into the mix in relation to CLL but it clearly has its proven health advantages particularly around metabolic syndrome and the inflammatory effects of high carb and sugar intake.

I’m afraid a purist ketogenic diet is too restrictive for me plus I’m wary of putting too much additional pressure on my kidneys from the higher protein intake.

Best wishes aremmick. I know you’re concerned about the ALC hike and hope you can gain some advice from your doctor on the implications of this. It doesn’t help when you’re already feeling very stressed as you’ve described in your earlier posts.

Best wishes,

Newdawn

[JR1964]

Neil, this was an interesting article from 2 years ago. I have also had personal experience with Metaformin. I am a diabetic Type 2. I was diagnosed in 2012 but have been well under controlled. In the March of 2017 my doctor seen fit to cut my Metaformin from 2000 mg a day to 1000mg a day. The diabetes was so well in control. In July , she decided to go from 1000mg to 500mg a day. Diabetes is still well in control. But started feeling not right. Like something the body was telling me. Just a sick feeling. Then in October I was diagnosed with CLL. Was the Metaformin holding the CLL in check?Was it just a coincidence? I know I approached my doctor about it and asked for her to look at my past blood tests for the last 6 years. She did and her response was the CLL look like it just happened. But when she said it , it was like see was hiding something. Dr. Weirda thinks it has been longer than just October of 2017. Personally, I think I had MBL for years. Metaformin held it in check till the dose got decreased. Next week, I am asking my doctor for all of my health records over the years. I want to see for myself. I had a ton of bloodwork done over the years. Mainly because I am a diabetic. Who knows? STAY STRONG J.R