A new study explores anti-aging properties of metformin

Research has found that metformin targets the chemicals produced by age-related senescent cells—normal cells that stop dividing and produce toxic substances damaging to the cells around them, said James Kirkland, director of the Robert and Arlene Kogod Center on Aging at the Mayo Clinic in Rochester, Minn., and part of the TAME planning team. Senescent cells usually develop as people age or at sites of age-related chronic diseases, such as the brain in Alzheimer’s patients or around the plaques that lead to heart attacks and strokes, he said. It isn’t proven if senescent cells actually cause the disease.
Metformin appears also to slow the development of age-related symptoms by increasing the enzyme AMP kinase, which normally declines with age, and decreasing the protein mTOR, which helps to regulate cell growth.

Scientists’ New Goal: Growing Old Without Disease

"For example, the type 2 diabetes medicine Metformin has been shown to extend the average lifespan of small animals by 5 percent and is believed to be safe and ready for human testing. "

I wonder what that 5% is equal to in human years?
Say average human LS is 80 years than an additional 4 years?
I guess the study has to be done and then the outcome will tell us if it is 5%, 10% or NO %...

Grantees in the News: AFAR Grantees Weigh-in on Longevity-Extending Drugs - American Federation for Aging Research

Metformin: New 'wonder drug' may help prevent lung cancer in smokers

April 19, 2010
Metformin, a safe and inexpensive drug widely used to lower blood glucose in Type 2 diabetics, may have a variety of other uses, researchers are finding. The newest, reported Monday at a Washington meeting of the American Assn. for Cancer Research, is to prevent lung cancer in smokers.
Metformin inhibits a hormone called insulin-like growth factor-1, or IGF-1, which explains its anti-diabetes activity. But IGF-1 also plays a crucial role in cancer development, and a variety of observational studies have hinted that, by blocking its activity, metformin may inhibit cancer. Studies have shown, for example, that women being treated for breast cancer who are also diabetic and taking metformin have a threefold better response to their chemotherapy. Researchers are now organizing a clinical trial to test its effects.
At an American Society of Clinical Oncology meeting on genitourinary cancers last month, Dr. Cristiano Ferrario of McGill University in Montreal, Canada, reported that metformin could inhibit the growth of prostate cancer cells in the laboratory -- albeit by inhibiting a different receptor.
Some observational studies have suggested that smokers who are diabetic and taking metformin are less likely to develop lung cancer. Dr. Phillip A. Dennis of the National Cancer Institute tested that idea by giving metformin to mice exposed to a tobacco carcinogen known as nicotine-derived nitrosamine, which normally induces tumors in experimental animals quite easily. He reported at Monday's meeting that administering the drug orally reduced tumor burden by 40% to 50%. Injecting it reduced the burden by 72%. The levels of metformin used in the mice are easily achievable in humans and are not associated with significant side effects, he said.
Some other studies have suggested that metformin may also reduce cardiovascular disease not directly related to diabetes. The problem with all these studies is that metformin is now a generic drug, so there is no incentive for pharmaceutical companies to launch an expensive clinical trial to demonstrate the drug's utility when they would not be the exclusive beneficiary of their findings.
-- Thomas H. Maugh II

I am starting 500 mg twice per day soon. I will be monitoring my glucose with a meter before I start for a few days and then while I am on it. I want to lose some visceral fat.

Metformin in the Treatment of HIV Lipodystrophy Syndrome

Treatment options for HIV-associated central fat accumulation - PubMed

Was this an observational study?

I deal with colitis and my doctor said Metformin can cause significant diarrhea, something I don't want to complicate my life with! Nelson, I hope you'll keep us posted as your protocol unfolds.

CoastWatcher, colitis give up all grains for a month, I bet you'd be surpised what a difference it would make.

I would recommend that you try the Metformin XR (Extended Release) version - no diarrhea that way. I have tried both and definitely recommend the XR version over the standard.

Thanks, ERO.

Two days...so far no diarrhea. I hope it stays that way since I have a very weak gut!

Nature | News

Anti-ageing pill pushed as bona fide drug

Regulators asked to consider ageing a treatable condition.


17 June 2015



Doctors and scientists want drug regulators and research funding agencies to consider medicines that delay ageing-related disease as legitimate drugs. Such treatments have a physiological basis, researchers say, and could extend a person's healthy years by slowing down the processes that underlie common diseases of ageing — making them worthy of government approval. On 24 June, researchers will meet with regulators from the US Food and Drug Administration (FDA) to make the case for a clinical trial designed to show the validity of the approach.
Current treatments for diseases related to ageing “just exchange one disease for another”, says physician Nir Barzilai of the Albert Einstein College of Medicine in New York. That is because people treated for one age-related disease often go on to die from another relatively soon thereafter. “What we want to show is that if we delay ageing, that's the best way to delay disease.”
Barzilai and other researchers plan to test that notion in a clinical trial called Targeting Aging with Metformin, or TAME. They will give the drug metformin to thousands of people who already have one or two of three conditions — cancer, heart disease or cognitive impairment — or are at risk of them. People with type 2 diabetes cannot be enrolled because metformin is already used to treat that disease. The participants will then be monitored to see whether the medication forestalls the illnesses they do not already have, as well as diabetes and death.
On 24 June, researchers will try to convince FDA officials that if the trial succeeds, they will have proved that a drug can delay ageing. That would set a precedent that ageing is a disorder that can be treated with medicines, and perhaps spur progress and funding for ageing research.
During a meeting on 27 May at the US National Institute on Aging (NIA) in Bethesda, Maryland, Robert Temple, deputy director for clinical science at the FDA's Center for Drug Evaluation and Research, indicated that the agency is open to the idea.
“What we're trying to do is increase health span, not look for eternal life.”

Barzilai and his colleagues eschew claims of a quest for immortality, because they think that such assertions have led to a perception that the field is frivolous and irresponsible. “The perception is that we are all looking for a fountain of youth,” says Stephanie Lederman, executive director of the American Federation for Aging Research in New York. “We want to avoid that; what we're trying to do is increase health span, not look for eternal life.”
Ageing research has hit bumps in the past decade, as companies marketing drugs touted to prolong life have gone bust (see Nature 464, 480–481; 2010). But organizers of the TAME trial think that the field is now in a better position because animal studies have shown that some drugs and lifestyle practices can extend life by targeting physiological pathways[SUP]1[/SUP].
For instance, the NIA-sponsored Interventions Testing Program, in which investigators at three sites are systematically trialling candidate age-delay treatments, has shown that a handful of interventions convincingly and reproducibly prolong the lives of various strains of mice. Those include cutting down on calorie intake and taking a drug called rapamycin that is used to prevent rejection of transplanted organs.
And researchers from the Novartis Institutes for Biomedical Research in Cambridge, Massachusetts, reported in December that elderly people develop a stronger immune response to an influenza vaccination if they also take a rapamycin-like drug[SUP]2[/SUP]. Rapamycin, which acts on a biological pathway involved in cell growth, is now seen as one of the most promising drugs for delaying ageing, but given over long periods of time it also suppresses the immune system.

Safety first

The TAME test is for metformin, which suppresses glucose production by the liver and increases sensitivity to insulin. The drug has been used for more than 60 years and is safe and prolongs healthy life and lifespan in worms[SUP]3[/SUP] and in some mouse strains[SUP]1[/SUP]. Data also suggest that it could delay heart disease, cancer, cognitive decline and death in people with diabetes[SUP]4[/SUP]. Plans call for the trial to enrol 3,000 people aged 70–80 years at roughly 15 centres around the United States. The trial will take 5–7 years and cost US$50 million, Barzilai estimates, although it does not yet have funding.
Matt Kaeberlein at the University of Washington, Seattle, who is running a trial of rapamycin in elderly dogs, says that the concept behind Barzilai's trial is sound. Even though other drugs might be more effective at delaying ageing in animal studies, he says, the many years of experience with metformin in people, combined with data suggesting that it impacts the ageing process in people, make it a good candidate for a first clinical trial in the field.
“It's a smart way to engage the FDA in a discussion about recognizing ageing as an indication that is appropriate for clinical trials,” Kaeberlein says.

My GP wanted to prescribe Metformin to me because statins used over a 15 year period had caused my blood sugar A1C to reach 6.4. (Pre-Diabetes). I told my GP "No, let me try TRT first.......I don't want to take any drugs right now." That was about 7 months ago before I knew anything about Metformin. I may call him back now and ask him to write the script for me. Besides the improved insulin regulation from Metformin.......on the reducing visceral fat feature.......do you think it will also reduce the last little layer if you are already lean? Silly question when you look at all the other great things this drug can do......but I'm just curios.

Nelson,

What was the outcome of your experiment.

What was the impact on your blood sugar?

"I am starting 500 mg twice per day soon. I will be monitoring my glucose with a meter before I start for a few days and then while I am on it. I want to lose some visceral fat."

The effect of testosterone on cardiovascular risk factors in men with type 2 diabetes and late-onset hypogonadism treated with metformin or glimepiride



Abstract

Background

Men with type 2 diabetes are often characterized by abnormal plasma testosterone levels. This study was aimed at investigating whether testosterone treatment has an impact on cardiovascular risk factors in patients with type 2 diabetes and late-onset hypogonadism (LOH), chronically treated with hypoglycemic agents.

Methods

This study included 51 men with type 2 diabetes, 26 of whom had already been treated with metformin and 25 with glimepiride for at least 6 months. On the basis of patient preference, 15 men receiving metformin and 12 receiving glimepiride were treated with intramuscular testosterone enanthate (100 mg weekly) for 12 weeks. Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were determined before and at the end of the study.

Results

With the exception of insulin sensitivity, plasma hsCRP and homocysteine, there were no differences between patients treated with metformin and glimepiride. Testosterone enanthate administered to both groups of patients increased plasma testosterone, reduced plasma hsCRP and improved insulin sensitivity. Testosterone-metformin combination therapy reduced also circulating levels of uric acid, homocysteine and fibrinogen. These effects, stronger in patients treated with metformin than glimepiride, correlated with the impact of testosterone on insulin sensitivity.

Conclusions

Our results suggest that testosterone may bring more clinical benefits to metformin- than sulfonylurea-treated men with diabetes and LOH.

Nelson Vergel said:

The effect of testosterone on cardiovascular risk factors in men with type 2 diabetes and late-onset hypogonadism treated with metformin or glimepiride



Abstract

Background

Men with type 2 diabetes are often characterized by abnormal plasma testosterone levels. This study was aimed at investigating whether testosterone treatment has an impact on cardiovascular risk factors in patients with type 2 diabetes and late-onset hypogonadism (LOH), chronically treated with hypoglycemic agents.

Methods

This study included 51 men with type 2 diabetes, 26 of whom had already been treated with metformin and 25 with glimepiride for at least 6 months. On the basis of patient preference, 15 men receiving metformin and 12 receiving glimepiride were treated with intramuscular testosterone enanthate (100 mg weekly) for 12 weeks. Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were determined before and at the end of the study.

Results

With the exception of insulin sensitivity, plasma hsCRP and homocysteine, there were no differences between patients treated with metformin and glimepiride. Testosterone enanthate administered to both groups of patients increased plasma testosterone, reduced plasma hsCRP and improved insulin sensitivity. Testosterone-metformin combination therapy reduced also circulating levels of uric acid, homocysteine and fibrinogen. These effects, stronger in patients treated with metformin than glimepiride, correlated with the impact of testosterone on insulin sensitivity.

Conclusions

Our results suggest that testosterone may bring more clinical benefits to metformin- than sulfonylurea-treated men with diabetes and LOH.

Click to expand...

Very nice news. Looks like Metformin and TRT go great together.......this is particular good news for me because I'm am in metabolic syndrome (high cholesterol) and high blood sugar.

Orrin Israel said:

"For example, the type 2 diabetes medicine Metformin has been shown to extend the average lifespan of small animals by 5 percent and is believed to be safe and ready for human testing. "

I wonder what that 5% is equal to in human years?
Say average human LS is 80 years than an additional 4 years?
I guess the study has to be done and then the outcome will tell us if it is 5%, 10% or NO %...

http://www.afar.org/news/view/grant...antees-weigh-in-on-longevity-extending-drugs/

Click to expand...

Or 0%. Small animals are one thing - humans are something entirely else. Some prior candidates such as resveratrol quietly dropped out because the tests did not pan out well - due to bioavaibility issues.

Effects of Sulfonylurea as Initial Treatment on Testosterone of Middle-Aged Men with Type 2 Diabetes: A 16-Week, Pilot Study

AIMS/INTRODUCTION: To evaluate the effect of sulfonylurea (glimepiride)-based oral antidiabetic agents on testosterone levels in middle-aged men with type 2 diabetes.

MATERIALS AND METHODS: As a substudy, 15 participants from the phase IV clinical trial of glimepiride (GREAT study) of middle-aged men with type 2 diabetes were included in the current study.

After enrolment, the initial dose of oral glimepiride was 1 mg/day. The dose was titrated according to blood glucose levels and the participants were treated for 16 weeks.

Meanwhile, another 15 healthy age- and body mass index-matched male subjects were randomly selected as the healthy control group.

RESULTS: Compared with the healthy control group, the middle-aged men with type 2 diabetes had significantly decreased total testosterone levels and a lower testosterone secretion index.

Blood glucose and lipid profile levels were significantly improved after 16 weeks of treatment with no significant differences in bodyweight and waist circumference compared with baseline values.

Recorded changes in luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin levels were not statistically significant. However, total testosterone levels were significantly increased and testosterone secretion index values were significant higher than those of the baseline.

CONCLUSIONS: It is highly possible that sulfonylurea as an initial treatment can recover the decreased total serum testosterone levels and testosterone secretion index values in middle-aged men with type 2 diabetes.

Wong L, Chen HM, Lai SQ, Yang HZ, Kuang J, et al. Effects of sulfonylurea as initial treatment on testosterone of middle-aged men with type 2 diabetes: A 16-week, pilot study. J Diabetes Investig. 2015;6(4):454-9.

[h=3][/b]The Effect of Metformin and Metformin-Testosterone Combination on Cardiometabolic Risk Factors in Men with Late-onset Hypogonadism and Impaired Glucose Tolerance
Exp Clin Endocrinol Diabetes 2015; 123(10): 608-613

[h=3]Abstract[/b]No previous study has investigated the effect of metformin, administered alone or together with testosterone, on cardiometabolic risk factors in men with hypogonadism. The study included 30 men with late-onset hypogonadism (LOH) and impaired glucose tolerance (IGT) who had been complying with lifestyle intervention. After 12 weeks of metformin treatment (1.7 g daily), the participants were allocated to one of 2 groups treated for the following 12 weeks with oral testosterone undecanoate (120 mg daily, n=15) or not receiving androgen therapy (n=15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were determined before and after 12 and 24 weeks of therapy with the final dose of metformin. Patients with LOH and IGT had higher levels of hsCRP, homocysteine and fibrinogen than subjects with only LOH (n=12) or only IGT (n=15). Metformin administered alone improved insulin sensitivity, as well as reduced 2-h postchallenge plasma glucose and triglycerides. Testosterone-metformin combination therapy decreased also total and LDL cholesterol, uric acid, hsCRP, homocysteine and fibrinogen, as well as increased plasma testosterone. The effect of this combination therapy on testosterone, insulin sensitivity, hsCRP, homocysteine and fibrinogen was stronger than that of metformin alone. The obtained results indicate that IGT men with LOH receiving metformin may gain extra benefits if they are concomitantly treated with oral testosterone.

Metformin-interesting read

Medical researchers say that the drug metformin, used for treating type 2 diabetes, could become the world's first anti-aging drug that enables adults to live well beyond 120 years. According to experts, the drug could extend healthy life and lifespan, and stave off illnesses associated with aging, such as Alzheimer's and Parkinson's disease.


Scientists believe that metformin, the world's most widely-used diabetes drug, is a good candidate for an anti-aging drug because tests conducted using animals demonstrated the ability of the drug to slow down the aging process.
Metformin, which suppresses glucose production in the liver and increases sensitivity to insulin, has been used for more than six decades to treat type 2 diabetes and is considered a safe drug for humans.
Recent tests, which show that metformin prolongs the lifespan and health of certain species of worms and strains of laboratory mice, have sparked interest in the drug as a possible anti-aging drug.
A series of tests, conducted by a team of Belgian researchers on a species of roundworms, C. elegans, found that metformin prolonged the lives of the roundworms by making them age more slowly and keeping them healthier for longer.
Other trials found that it also prolongs the healthy life and lifespan of certain strains of mice.

Read more at Diabetes Drug Metformin Could Increase Human Lifespan To 120 Years
Experts at Cardiff University in the U.K. also pointed to anecdotal evidence that human patients treated with metformin for diabetes live longer than expected, often longer than people without diabetes. The anecdotal evidence is paradoxical because diabetes normally shortens lifespan, as sufferers have a heightened susceptibility to cardiovascular diseases and kidney complications.Based on results of tests on animals, scientists believe metformin could also make humans live beyond 120 years.
Researchers plan to conduct the first clinical trials of the project, dubbed Targeting Aging with Metformin (TAME), next year to see whether results obtained in animals can also be replicated in humans. Researchers are hopeful of a major breakthrough in the decades-long search for an anti-aging drug.
The study, to be conducted in the U.S., will involve 3,000 adults aged 70- to 80-years-old, with known risk of cancer, heart disease, and neurodegenerative diseases that cause cognitive impairment, and people who already have one or a combination of the conditions.
The individuals will be placed on the drug and monitored to see if it exerts significant preventive effect on the disease conditions, or whether it affects the progress of the conditions and overall lifespan of participants.

Read more at Diabetes Drug Metformin Could Increase Human Lifespan To 120 Years

Stop the Metformin Madness

Jun 18, 2015 by Chandler Marrs, PhD


I have never been a fan of Metformin. It seemed too good to be true. Many years ago I had a conversation with a researcher about all of its possible therapeutic indications. His lab was actively pursuing the anti-cancer angle. That should have been a clue that Metformin might be causing more damage than we recognized, but it wasn't. At that point, I was still enamored with the wonders of pharmacology and hadn't yet begun my path toward understanding medication adverse reactions. Indeed, it wasn't until very recently, when a family member began suffering from one of these reactions, that I began my investigation in full. This is what I learned.

Stop the Metformin Madness- Hormones Matter



Comments, anyone?