instalment 9: prescription medications that may be helpful in certain situations

There are some medications that you may want to consider asking your doctor to prescribe:

Metformin

Metformin, first used in the 1950s, is a first line treatment for type 2 diabetes and probably the most widely used oral antidiabetic medication. It was shown to be a potential drug candidate for treating a range of other diseases that include various cancers, cardiovascular diseases, diabetic kidney disease, neurodegenerative diseases, renal diseases, obesity, inflammation, COVID-19 in diabetic patients, and aging¹.

All of these effects can be ascribed to the insulin lowering effects of metformin, which can also explain the finding in experimental animals (C. Elegans worms) of increasing healthy lifespan by up to a third, probably by altering the metabolism of bacteria in the worm gut².

This is likely the mechanism by which it lowers insulin (by stimulating bacteria in the duodenum and small intestine to take up and ferment glucose, less of that glucose will be available for absorption into the body, and so less glucose to stimulate insulin release).

As for any medication, there are side effects. For example, metformin reduces testosterone levels³, and it impairs vitamin B12 absorption⁴ making B12 supplementation a necessity.

If metformin has so many benefits, why is is not used more? Let me tell you a little story.

As many readers may know, my wife Helen was diagnosed with colon cancer in 2017. In spite of surgery, the cancer returned, and chemotherapy ultimately was unhelpful. I accompanied Helen to most of her appointments with her physicians and other health workers, and at one visit with her oncologist, I asked him about metformin (I had become aware of this medication in my researches into extending healthy lifespan). He told us that metformin had been shown not to be helpful in pancreatic cancer, and that a colleague of his was coauthor on the paper that reported this negative result. I expressed surprise at this, and after we returned home, I looked up the article and was even more surprised. I documented what I learned in the essay “When medical research reports negative findings: follow the money!”.

Unfortunately, this bias towards reporting negative results for treatments which will not profit the industry is continuing. I found this article, with the title “Low-Dose Metformin as a Monotherapy Does Not Reduce Non-Small-Cell Lung Cancer Tumor Burden in Mice”⁵. The abstract does not mention low dose at all, and the article itself, on careful reading, tells us that the mice were given metformin only twice a week, instead of the usual daily dosing. Well, no wonder it didn’t work! The study seems to have been designed so that metformin would fail, and the authors’ omission of the low dose in the abstract strikes me as misleading.

In any case, reporting of negative results in ways intended to discourage use of cheap but effective remedies is only one of the ways industry has come up with to increase profits. I’d read a most interesting book, titled “Deadly medicines and organized crime: how big pharma has corrupted healthcare,” by Dr. Peter Gøtzsche. Dr. Gøtzsche, a specialist in internal medicine and professor at the University of Copenhagen, had co-founded the Cochrane Collaboration in 1993 and established the Nordic Cochrane Centre. Follow this link to read my review of his book, in which I describe four strategies used by industry.

In the foreword, I mentioned that prior to 2012, I had been following a low-carb diet, and that this diet had stopped working for me. But it had worked for many years, as I described in this article that was published in the Nutrition Post in 1998: “Metabolic mayhem: Hunter-gatherers trapped in an agrarian age”. But why was it no longer working? I think the answer was that I, along with many other low-carbers, had bought into the “fat is bad” idea (see my talk “Why we get old and die, and what to do about it”) and as a consequence tended to replace carbs with protein. And protein in the diet stimulates the secretion of IGF-1, which acts much like insulin, and therefore causes weight gain.

And that’s more than enough for one day! So let’s end instalment 9 here, and in the next instalment we’ll get to a couple of other medications which lower insulin.

If you have a little more patience, I’ll share with you a question I posted on ResearchGate 6 years ago, an online platform for researchers to post their work and collaborate with other researchers:

What is the evidence that insulin resistance in type 2 diabetes and in metabolic syndrome is NOT caused by hyperinsulinemia?

When I was a medical student at McGill in the late 1970s, we learned a straightforward explanation for the cause of Type 2 diabetes, the most common form of diabetes in adults, accounting for about 90 per cent of all diabetes cases. We were told the insulin resistance responsible for Type 2 diabetes was caused by high levels of insulin. Hyperinsulinemia–increased insulin levels in the blood–was said to “downregulate” insulin receptors, making cells with those receptors less responsive to the insulin message. From a physiology point of view, this makes perfect sense. It’s analogous to the development of tolerance that can happen with regular heroin use when a person no longer responds to the drug in the way they did initially.

Sometime in the 1980s this explanation for the cause of insulin resistance was abandoned. Instead, the medical community adopted a new theory that insulin resistance comes first, and is behind high insulin levels in Type 2 diabetes. To overcome insulin resistance, the pancreas secretes larger-than-normal amounts of insulin, resulting in so-called “reactive hyperinsulinemia.” The cause of this insulin resistance is never clearly explained, although obesity, chronic inflammation, and genes are all said to contribute.

When I ask prominent endocrinologists about how insulin resistance comes about in this new paradigm, they say, sometimes condescendingly: “It’s too complicated for a psychiatrist to understand.” That may be. But I’m also an engineer, and when I studied at the University of Waterloo the saying was “BBB”, short for “Bullshit Baffles Brains.” I consider myself to be a critical thinker, so if the new explanation for what causes insulin resistance is incomprehensible to me, that’s probably because it’s nonsense.

Why did the medical community make a 180-degree reversal of its theory for the cause of Type 2 diabetes? Why discard a nice, coherent, easy-to-test explanation and replace it with a theory no one seems able to describe in terms that an engineer and physician can understand? Time to apply another useful saying: “Follow the money.”

Who profits from this paradigm shift? To answer this question, let’s compare the consequences of diabetes management approaches under the old paradigm and the new one. If we follow the old theory that high insulin levels cause insulin resistance, then treatment involves lowering insulin levels, assuming that insulin resistance is reversible. Since the main stimulus to insulin secretion is the level of glucose in the blood, we can get the pancreas to release less insulin by decreasing the amount of glucose going into the bloodstream. For people who eat regularly, that main source of blood glucose is carbohydrates in the diet, i.e., sugars and starches.

Treatment options for lowering blood glucose include medications such as acarbose, which reduces the absorption of dietary carbohydrates in the small bowel. Metformin, the first-line treatment of choice for Type 2 diabetes, is believed to have a similar effect and may also contribute to weight loss. Traditional and folk remedies for obesity and Type 2 diabetes, including yerba maté tea and the gourd bitter melon, may act in the same way. An easier route for some would be to lower the amount of carbohydrates in the diet, and/or pick foods with a low glycemic index. Research demonstrates a low-carb diet can reduce or even eliminate the need for medication to control blood sugar, in effect, curing diabetes in some patients, and, more importantly, showing that Type 2 diabetes is likely caused by diet for people with susceptible genes.

If we follow the new paradigm and believe obesity, inflammation and genes cause insulin resistance, what can we do? Lose weight? Many find this impossible. Reduce inflammation? Difficult if we don’t know its cause. Change our genes? Maybe in the future. Typically the victim is blamed for overeating and not exercising enough. In the absence of effective ways to reduce insulin resistance in this paradigm, the usual solution is medication to control blood sugar levels.

Some commonly prescribed anti-diabetic medications stimulate the pancreas to produce more insulin, while others act at the level of the insulin receptor to decrease insulin resistance. And of course, insulin itself, typically given in amounts way larger than what the pancreas secretes in normal individuals, can help people overcome insulin resistance. Yes, blood sugar levels will decrease. But there are side effects: insulin itself, and many of the medications that increase insulin or increase its effectiveness, may cause weight gain. And if obesity is a cause of insulin resistance, there is no way these treatments can stop a patient’s diabetes. Instead, for many victims, the diabetes just gets worse.

So let’s follow the money. If today’s treatment approaches don’t cure diabetes and may even make it worse, who benefits? Drug companies, who gain customers for life due to diabetes and its many complications, including vascular disease, dementia, kidney and eye problems, even cancer. Medical device manufacturers profit when diabetic patients need cardiac pacemakers, artificial valves, and prosthetic limbs. Kidney failure requires expensive machines, products and dialysis facilities. Many professions, including physicians, pharmacists, dietitians, physiotherapists, social workers, occupational therapists, and others are called upon to provide care and diabetics need hospitals, clinics, blood test labs, MRI machines, offices, exercise machines, and more. Simply put, the new paradigm is good for the economy. It’s too bad that patients must suffer.

If the theory that high insulin levels cause insulin resistance has no scientific basis, where is the research disproving this hypothesis? And why aren’t the current treatment approaches truly helping Type 2 diabetics fight a disease that has huge health consequences? I don’t mind being wrong. Show me the evidence!

This posting had over 3000 reads, and got 39 replies. Eventually I stopped responding, because it felt to me that the most persistent respondent, who insisted I was wrong but couldn’t provide proof, was basically saying that I just couldn’t understand his “truth”. Sigh!

1. Ala M. Metformin for Cardiovascular Protection, Inflammatory Bowel Disease, Osteoporosis, Periodontitis, Polycystic Ovarian Syndrome, Neurodegeneration, Cancer, Inflammation and Senescence: What Is Next. ACS Pharmacol Transl Sci. 2021;4:1747-1770. PMID 34927008
   Shoshan-Barmatz V, Anand U, Nahon-Crystal E, Di Carlo M, Shteinfer-Kuzmine A. Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target. Front Physiol. 2021;12:730048. PMID 34671273 ↩
2. Cabreiro F, Au C, Leung KY et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell. 2013;153:228-239. PMID 23540700 ↩
3. Shegem NS, Nasir AM, Jbour AK, Batieha AM, El-Khateeb MS, Ajlouni KM. Effects of short term metformin administration on androgens in normal men. Saudi Med J. 2002;23:934-937. PMID 12235466 ↩
4. de Jager J, Kooy A, Lehert P et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010;340:c2181. PMID 20488910 ↩
5. Bond NLS, Dréau D, Marriott I et al. Low-Dose Metformin as a Monotherapy Does Not Reduce Non-Small-Cell Lung Cancer Tumor Burden in Mice. Biomedicines. 2021;9:1685. PMID 34829914 ↩

• ← instalment 8: more useful dietary supplements
• instalment 10: more prescription medications that may be helpful in certain situations →