Metformin And Alzheimer’s: A Potential New Therapy?
The diabetes drug may have a beneficial effect on neurodegenerative diseases. Metformin, a biguanide, is an oral diabetes medicine used to improve blood glucose levels in people with type 2 diabetes. There have been various studies on other uses of metformin. It may be beneficial in Alzheimer’s disease, stroke and other degenerative brain cell diseases. An animal study found that metformin helps neurogenesis and enhances hippocampus, a key pathway (aPKC-CBP). Type 2 diabetes doubles the risk of having dementia; though some studies show metformin helps reduce risk, other studies show antidiabetic medications like insulin are linked to increased risk of having dementia. Animal studies show that metformin recruits endogenous neural stem cells and also promotes the genesis of new neurons. Metformin, however, needs to have been used for a longer period before a drastic reduction in neurodegenerative disease and its neuroprotective nature is seen. The purpose of this study is to find a link between antidiabetic medications, especially metformin and other neurodegenerative diseases. Also, to know how long one has to be on these antidiabetics before the neuroprotective nature kicks in. A cohort study of type 2 diabetes patients who are 55 years and above and being managed on a monotherapy antidiabetic drug of either metformin, sulfonylurea (SU), thiazolidinedione (TZD) or insulin were observed in a period of 5 years. In the course of 5 years, dementia was identified in 9.9% of the patients. Comparing those taking metformin to those taking sulfonylurea, there was a 20% reduction in dementia in those taking metformin. The hazard ratio 0.79%, a 95% confidence interval of 0.65-0.95. For TZD, metformin had a 23% reduction in having dementia as compared to TZD with hazard ratio of Continue reading >>
Diabetes Drug May Protect The Brain
HealthDay Reporter MONDAY, July 15 (HealthDay News) -- The diabetes drug metformin may do more than help control blood sugar levels: New research suggests it may also reduce the risk of dementia. Compared to people taking another class of diabetes medications called sulfonylureas, those taking metformin had a 20 percent reduced risk of developing dementia over the five-year study period. "Metformin could have a possible neuroprotective effect in the brain," said study author Dr. Rachel Whitmer, an epidemiologist in the division of research at Kaiser Permanente in Oakland, Calif. Whitmer, however, added a caveat: "This was an observational, retrospective, population-based study. We found an association, but didn't prove cause and effect." Whitmer is scheduled to present the findings Monday at the Alzheimer's Association International Conference in Boston. Research presented at medical meetings should be viewed as preliminary until published in a peer-reviewed journal. People with type 2 diabetes have double the risk of developing dementia compared to someone without diabetes, according to background information in the study. But, even though diabetes is such a significant risk factor for dementia, the researchers found that there was little research on the effect of diabetes medications on dementia risk. To see if any therapies might offer some protection against dementia, Whitmer and her colleagues reviewed data on nearly 15,000 people with type 2 diabetes who were just starting single-drug therapy for their disease. All of those included in the study were aged 55 or older, and all had been diagnosed with type 2 diabetes. Whitmer said none of them were newly diagnosed; some had even been diagnosed with type 2 diabetes as long as 10 years earlier. But none had been takin Continue reading >>
Metformin Linked To Reduced Dementia Risk In Veterans With Type 2 Diabetes
Metformin Linked to Reduced Dementia Risk in Veterans With Type 2 Diabetes Metformin Linked to Reduced Dementia Risk in Veterans With Type 2 Diabetes Up to 60% of people with diabetes will develop dementia. The use of metformin in older patients with type 2 diabetes is associated with a lower risk for dementia compared with the use of a sulfonylurea, according to the results of a retrospective cohort study published in Neurology. A cohort of US veterans age 65 with type 2 diabetes , who were new users of either metformin or a sulfonylurea and did not have dementia, were enrolled in the study. Follow-up took place after 2 years of treatment. In order to account for confounding by indication, the investigators developed a propensity score (PS) and utilized inverse probability of treatment weighting (IPTW) methods. The hazard ratio (HR) of incident dementia was estimated via Cox proportional models. The researchers identified 17,200 new users of metformin and 11,440 new users of a sulfonylurea (mean age, 73.5; mean HbA1c, 6.8%). A total of 4906 cases of dementia were diagnosed over 5-year follow-up period, with 2177 (12.7%) in metformin users and 2729 (23.9%) in sulfonylurea users. The crude HR for any dementia diagnosed in metformin vs sulfonylurea users was 0.67 (95% CI, 0.61-0.73; P <.001) and 0.78 (95% CI, 0.72-0.83; P <.001) in patients age <75 and 75, respectively. After adjustment, the results continued to be statistically significant in veterans age <75 (HR 0.89; 95% CI, 0.79-0.99; P =.033) but not in veterans 75 (HR 0.96; 95% CI, 0.87-1.05; P =.332). A significantly lower risk for developing dementia was also observed in a subset of younger, white veterans with hemoglobin A1c (HbA1c) levels 7% (HR 0.76; 95% CI, 0.63-0.91; P =.003) and with normal renal function ( Continue reading >>
Metformin Linked To Dementia, Parkinson's In Patients With T2dm
Metformin Use Linked to Increased Dementia, Parkinson's Risk in Patients With Diabetes VIENNA, Austria — Long-term use of the diabetes medication metformin may increase the risk for neurodegenerative disease in patients with type 2 diabetes mellitus (T2DM), new research suggests. In a cohort study that followed about 9300 patients with T2DM in Taiwan for up to 12 years, the risk for Parkinson's disease (PD) or Alzheimer's dementia was more than double during a 12-year period for those who took metformin vs those who did not — even after adjusting for multiple confounders. In addition, outcome risks increased progressively with higher dosage and longer duration of treatment. The results were presented here at AD/PD 2017: The 13th International Conference on Alzheimer's and Parkinson's Diseases by Yi-Chun Kuan, MD, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. Interestingly, recent research has suggested that use of metformin may protect against neurodegenerative diseases. When asked about that, Dr Kuan told Medscape Medical News that "some studies have actually found positive [outcomes] but some have been negative ." So the researchers wanted to look into this using their own data. "We'd heard about a possible protective effect from metformin. However, we found the reverse," she said, but stressed that large-scale, prospective studies in other countries are needed to clarify the results. The investigators note that past research has shown a link between T2DM and increased risk for neurodegenerative diseases, but there's been "some question" about the association with specific diabetes medications. They examined records for patients with T2DM from the National Health Insurance research database of Taiwan, including 4651 who had metformin pre Continue reading >>
Metformin And Alzheimer's Disease, Dementia And Cognitive Impairment: A Systematic Review Protocol
The disease burden of dementia in Australia has been estimated to total 121,737 disability adjusted life years (DALYs), making dementia the fourth leading cause of burden from disease in this context. 1 Alzheimer's disease is the most common form of dementia, representing 50% to 75% of cases. 1 Due to the aging population, this increasing prevalence of dementia is not expected to decline without a major breakthrough in prevention. Another disease with a troublingly high prevalence is diabetes, which affects around 5% of the population. 2 Diabetes has been strongly linked to the onset of dementia and Alzheimer's disease. 3 A meta-analysis of 28 longitudinal studies demonstrated that people with diabetes had a 73% increased risk of developing dementia and a 56% increased risk of developing Alzheimer's disease compared to the general population. 3 There is evidence supporting a number of different mechanisms that may underlie this association including: inflammation, oxidative stress, vascular effects (influencing the circulation of blood to the brain), increased cerebral -amyloid peptides, hyperinsulinemia, brain insulin resistance and the formation of advanced glycation end-products. 4-6 Ultimately, it is likely that the cause is multifactorial, however, a clearly influential factor is elevated blood glucose, which occurs as a direct consequence of diabetes and has been shown to cause impaired episodic memory even in people who do not have diabetes. 7 The biguanide metformin, a first-line antidiabetic drug for type 2 diabetes, acts as an insulin sensitizer and reduces blood glucose by increasing glucose uptake into muscles while reducing liver gluconeogenesis through the activation of AMP-activated protein kinase (AMPK). 8 The seminal study supporting the contemporary p Continue reading >>
Metformin Use Does Not Help Beat Cognitive Impairment As Previously Thought
Metformin use does not help beat cognitive impairment as previously thought Metformin use does not help beat cognitive impairment as previously thought Omega-3 fatty acids shown to reverse islet autoimmunity in mice 05 April 2017 A new large-scale study has found that long-term metformin use does not help slow down cognitive decline in diseases of the aging brain. The findings are of importance because diabetes is a risk factor for a number of neurodegenerative diseases, and metformin , the first-line drug treatment for type 2 diabetes , may affect an important aspect of cognitive impairment in older adults. Scientists knew that having decreased insulin sensitivity negatively impacts memory formation and prevents insulin from doing its job, including preventing the build-up of plaque in Alzheimer's disease. Some studies hinted that short-term use of metformin might actually protect from cognitive impairment as the treatment helps correct insulin issues and promotes the formation of new neurons. This new research, however, suggests that this protective effect from metformin may be true only for a limited period of time. After following a total of 9,300 patients with type 2 diabetes for 12 years, Taiwanese researchers at Taipei Medical University found that long-term metformin increased the risk of both Parkinson's and Alzheimer's disease . The study showed that the longer a patient used metformin, here for more than 300 days and at doses greater than 240g, the higher the odds of developing these diseases later in life. In fact, the risk for Parkinsons disease or Alzheimers dementia went up over 50 per cent during a 12-year period in those who took metformin when compared to those who did not. The higher incidences of Parkinsons and Alzheimer's dementia were still signif Continue reading >>
Metformin And Neurodegenerative Diseases
Its one of the most widely used prescription drugs in the world, hailed for its ability to lower blood glucose levels, impressive safety profile, and low cost. Metformin the first-line oral drug for Type 2 diabetes has been prescribed in Europe since the 1950s and the United States since 1995, and achieved much of its formidable reputation through the UK Prospective Diabetes Study (UKPDS), published in 1998. But a new study may have slightly dimmed possibly just for a moment metformins bright halo. The study not yet published, but presented last week at the 13th International Conference on Alzheimers and Parkinsons Diseases in Vienna looked at about 9,300 people with Type 2 diabetes in Taiwan for up to 12 years. As noted in a Medscape article on the study , during the follow-up period, the risk of participants who took metformin developing Alzheimers or Parkinsons was more than twice as high as it was for those who didnt take the drug. This was true even after adjusting for certain characteristics like age and diabetes severity that might affect whether someone was taking metformin in the first place. The risk of developing Parkinsons disease, in particular, was 2.27 times as high in participants who took metformin as in those who didnt. The risk of dementia from all causes was 1.66 times as high, and the risk of Alzheimers in particular was 2.13 times as high. Overall, taking a higher dose of metformin and taking it for a longer duration were both associated with a higher risk of developing one of the measured conditions. For example, taking metformin for less than 180 days was associated with a 1.77-times-as-high risk of Parkinsons, while taking the drug for 400 days or longer was associated with a 4.49-times-as-high risk of Parkinsons. Similarly, taking metformin fo Continue reading >>
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Does Metformin Increase Dementia Risk?
Here is evidence that metformin, especially at high doses and for long periods, is associated with increased risk for neurodegenerative diseases and dementia. Metformin and Neurodegenerative Disease: An Unknown Link? O Epidemiological studies link T2D with increased risk for neurodegenerative diseases, like Alzheimer Disease (AD) and Parkinson Disease (PD) O Research is conflicting about whether metformin contributes to the increased risk for neurodegenerative diseases in T2D . Some studies have linked metformin to decreased risk of dementia  . Others suggest increased risk of AD with long-term metformin  Taiwanese Study Evaluated Risk for Dementia, PD with Metformin . Used insurance claims data from Taiwans National Health Insurance Research Database . Included patients 50 years, recently diagnosed with T2D O Minimized bias with propensity score matching; adjusted for age, sex, comorbidities, diabetes complications, medications PD and Dementia Risk Increased with Metformin 0 Parkinson disease: Significantly increased risk with metformin vs without . Risk over twice as high (HR 2.27, 95% CI 1.683.07, p<0.001) 0 All-cause dementia: Significantly increased risk with metformin . 66% increased risk (HR 1.66, 95% CI 1.352.04, p<0.001) 0 Alzheimers disease: Significantly increased risk with metformin . Risk over twice as high (HR 2.13, 95% CI 1.203.79, p<0.01) 0 Vascular dementia: Significantly increased risk with metformin . Risk over twice as high (HR 2.30, 95% CI 1.254.22, p<0.01) Longer Duration, Higher Dose Linked to Higher PD Risk 0 Longer Metformin Duration: Significantly increased risk for PD with metformin vs without . 180-299 days: 46% increased risk (HR 1.46, 95%CI 0.902.37, results NS) . 400 days: 4.5 times increased risk (HR 4.49, 95%CI 3.066.58, p<0.00 Continue reading >>
Metformin Causes Cell Death, Increases Risk For Alzheimer's Disease
The blockbuster drug, metformin, is considered effective, safe and cost-effective for priority conditions and a basic healthcare system. It is the most widely used medication for type 2 diabetes. While this drug was discovered nearly 100 years ago and considered safe and essential to medicine, recent research may turn this belief upside down. It should make you stop and think about that seemingly harmless drug and the subtle memory and cognitive changes that are attributed to normal aging. [Jump to: Nutritional Options] Metformin, a generic type 2 diabetes drug, and its brand name equivalents - Fortamet, Glucophage, Glucophage XR, Glumetza, and Riomet has at least three known adverse consequences. One is the well-known issue that metformin interferes with and depletes vitamin B12 and folate and raises homocysteine levels. This finding alone is enough to make this drug worrisome for anyone with methylation concerns, seniors, digestive concerns, or gastric bypass patients as these are commonly related with vitamin B12 and folate deficiency. The second concern is the build-up of lactic acid. Lactic acid can make muscles hurt, markedly increase fatigue and rarely be deadly. It reflects an insult to normal metabolism and aerobic energy production. The third recently discovered issue is piercing its way through medical research and raises serious concerns about metformin. Metformin Causes Mitochondrial Dysfunction and Nerve Cell Death Research published in the journal Aging, August 2016 is the latest article in a progression of cellular and animal studies that demonstrates increased risk of Alzheimer’s with chronic use of metformin. Metformin induces mitochondrial dysfunction and cell death in the brain by affecting several proteins, including beta-amyloid protein. These is Continue reading >>
Effect Of Insulin Sensitizer Metformin On Alzheimer's Disease Biomarkers
Summary Previous studies and Dr. Steven Arnold's laboratory work have shown that the brain in Alzheimer's disease is resistant to the healthy growth effects of insulin and that re-sensitizing brain cells to insulin may be a useful therapeutic strategy. Dr. Steven Arnold and colleagues have identified the anti-diabetes drug, metformin, as a safe medicine that enters the brain and re-sensitizes insulin receptors. This proposal seeks to conduct an efficient clinical trial with metformin in people with mild cognitive impairment and early dementia due to Alzheimer's disease to determine its effect on cognitive functioning and physiological and biochemical biomarkers of Alzheimer's disease. Details The goal of this project is to determine if treatment with a common FDA-approved insulin-sensitizing, anti-diabetes medicine—metformin—can improve cognitive abilities and modify physiological and biochemical abnormalities in people (without diabetes) who have mild cognitive impairment or early dementia due to Alzheimer's disease. These investigators have designed a brief, efficient, and sensitive clinical trial with a "crossover" design to detect beneficial effects of metformin for Alzheimer's disease. In this study, “crossover” refers to the fact that participants will be randomly assigned to two groups. One group will receive 8 weeks of metformin and then 8 weeks of placebo, while the second group will receive the reverse order. Both groups will have in-depth baseline assessments before starting on medication, then two other assessments—one after each metformin or placebo treatment. The study will measure memory and thinking abilities with a brief but very sensitive novel computerized cognitive test battery as well as several well established paper and pencil tests. To Continue reading >>
Metformin & Your Brain | Cognitive Vitality | Alzheimer's Drug Discovery Foundation
1 meta-analysis for Alzheimer's prevention 2 small clinical studies in patients with mild cognitive impairment or mild Alzheimer's disease 6 observational studies for future Alzheimer's risk in patients with type-2 diabetes Multiple observational studies have reported varying results on whether metformin may be beneficial for preventing Alzheimer's disease in type 2 diabetes patients. Three studies reported a decreased risk for cognitive impairment or dementia in diabetic patients taking metformin compared to those not taking medication or taking other diabetes drugs    . Additionally, one meta-analysis suggested a trend for reduced risk of dementia with metformin use in diabetics  . Three other studies, however, reported an increased risk for impaired cognitive performance, dementia, or Alzheimer's disease with metformin use compared to those taking other medications    . One study reported that longer metformin use was associated with an increasing risk for dementia  . Several factors could account for the varying results. Many of these studies do not account for diabetes duration, severity, or how well diabetes is controlled  . Also, metformin is often used to treat mild diabetes, so patients taking other drugs may have more severe diabetes. Additionally, long-term metformin use can decrease vitamin B12 levels, which may be a potential risk factor for Alzheimer's disease. One study reported that when controlling for vitamin B12 levels, metformin was no longer significantly associated with increased risk of Alzheimer's   . It is currently unknown whether metformin would prevent Alzheimer's disease in non-diabetic patients. Whether with metformin or another method, controlling diabetes is important for reducing your risk for Alzheimer' Continue reading >>
Metformin Might Cut Risk Of Alzheimers, Parkinsons
Metformin Might Cut Risk of Alzheimers, Parkinsons A large study finds those taking the drug for four years or more saw their risk of being diagnosed with a neurodegenerative disease lowered by 76%. New research out of Tulane University seems to suggest that metformin could be a tool to help combat Alzheimers disease, Parkinsons disease, and dementia. Researchers found that those taking metformin for two years or more enjoyed a substantial reduction in the risk of neurodegenerative diseases, according to PhD candidate Qian Shi. Based on these findings, its possible that prolonged use of metformin could potentially protect the neurons in the brain from degradation, said Shi, a research assistant at Tulane University School of Public Health and Tropical Medicine, who was speaking at the 2016 ADA Scientific Sessions. In a series of studies, Shi and others examined data from the U.S. Department of Veterans Affairs to compare neurodegenerative disease rates among metformin users and those not taking metformin. In the final study , 6,046 patients receiving treatment were followed from diagnosis until death or the conclusion of the study. Overall, participants were studied for an average of 5.25 years. For those not taking metformin, the reported incidence of developing a neurodegenerative disease was 2.08 per 100 individuals. That rate plummeted for metformin users those on metformin for two to four years had a diagnosis rate of just 1.30 per 100, and those taking it for four years or more had a diagnosis rate of just .49 per 100. The precise reasons metformin could protect the brain remain unclear, but researchers do know the drug is capable of crossing the blood-brain barrier. While this sounds like great news, it may be too early to administer metformin to all older Ameri Continue reading >>
Study: Metformin Linked To Higher Risk Of Alzheimer’s And Parkinson’s
A recent study found that the use of metformin in people with diabetes increased their risk for developing dementia and Parkinson’s Disease. This may be surprising as not too long ago, we reported on a different study which found the opposite–that using metformin might lower the risk for dementia in older men. The study from Taiwanese researchers was presented on March 29, 2017 at The 13th International Conference on Alzheimer’s and Parkinson’s Diseases in Vienna Austria by Dr. Yi-Chun Kuan from the Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. The researchers found that long-term use of metformin may raise the risk of neurodegenerative disease in those with type 2 diabetes. How Harmful Might Metformin Be to the Brain? As reported by Medscape Medical News, Yi-Chun Kuan and team conducted a cohort study to follow a total 9,300 patients with type 2 diabetes in Taiwan for up to 12 years. They checked records for these patients from the National Health research database of Taiwan including 4,651 who had metformin prescriptions and 4651 matched controls who didn’t take any metformin. Dr. Kuan told Medscape they adjusted for age, sex, and diabetes severity and that despite this, “the cumulative incidences of Parkinson’s and dementia were significantly higher for our metformin cohort” at 12 years. In fact, the risk for Parkinson’s disease or Alzheimer’s dementia went up over 50 percent during a 12 year period in those who took metformin when compared to those who did not. Researchers also found that “outcome risks increased progressively with higher dosage and longer duration of treatment.” Dr. Yi-Chun Kuan said, “We’d heard about a possible protective effect from metformin. However, we found the reverse,” and she added t Continue reading >>
Does Glucophage Make Alzheimers Worse?
Metformin, now theres a drug story for you. Its a startlingly small molecule , the sort of thing that chemists look and and say Thats a real drug? It kicked around in the literature and the labs in the 1960s, was marketed in Europe in the 1980s but was shopped around in the US for quite a while, partly because a lot of people had just that reaction. (It didnt help that a couple of other drugs in the same structural class turned out to cause lactic acidosis and had to be pulled from use). Bristol-Myers Squibb finally took metformin up, though, and did extremely well with it in the end under the brand name Glucophage. Its now generic, and continues to be widely prescribed for Type II diabetes. But for many years, no one had a clue how it worked. It not only went all the way through clinical trials and FDA approval without a mechanism, it was nearly to the end of its patent lifetime before a plausible mechanism became clear. Its now generally accepted that metformin is an activator (somehow, maybe through another enzyme called LKB1 ) of adenosine monophosphate kinase (AMPK), and that many (most?) of its effects are probably driven through that pathway. AMPKs a central player in a lot of metabolic processes, so this proposal is certainly plausible. But never think that you completely understand these things (and, as a corollary, never trust anyone who tries to convince you that they do). A new paper in PNAS advances the potentially alarming hypothesis that metformin may actually exacerbate the pathology of Alzheimers disease. This hasnt been proven in humans yet, but the evidence that the authors present makes a strong case that someone should check this out quickly. Theres a strong connection between insulin, diabetes, and brain function. Actually, there are a lot of stro Continue reading >>
Could A Diabetes Drug Help Beat Alzheimer's Disease?
Most of the 20 million people diagnosed with type 2 diabetes in the U.S. take metformin to help control their blood glucose. The drug is ultrasafe: millions of diabetics have taken it for decades with few side effects beyond gastrointestinal discomfort. And it is ultracheap: a month's supply costs $4 at Walmart. And now new studies hint that metformin might help protect the brain from developing diseases of aging, even in nondiabetics. Diabetes is a risk factor for neurodegenerative diseases, but using metformin is associated with a dramatic reduction in their incidence. In the most comprehensive study yet of metformin's cognitive effects, Qian Shi and her colleagues at Tulane University followed 6,000 diabetic veterans and showed that the longer a patient used metformin, the lower the individual's chances of developing Alzheimer's disease, Parkinson's disease, and other types of dementia and cognitive impairment. In line with some of the previous, smaller studies of long-term metformin use, patients in the new study who used the drug longer than four years had one quarter the rate of disease as compared with patients who used only insulin or insulin plus other antidiabetic drugs—bringing diabetics' risk level to that of the general population. The findings were presented in June at the American Diabetes Association's Scientific Sessions meeting. Even in the absence of diabetes, Alzheimer's patients often have decreased insulin sensitivity in the brain, says Suzanne Craft, a neuroscientist who studies insulin resistance in neurodegenerative disease at the Wake Forest School of Medicine. The association has led some people to call Alzheimer's “type 3 diabetes.” Insulin plays many roles in the brain—it is involved in memory formation, and it helps to keep synapses Continue reading >>