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Metformin

Metformin

Metformin is derived from the French Lilac plant called Galega officinalis. In the 1920’s, the active ingredient in this plant, known as guanidine compounds, were discovered and isolated. During that time, metformin was created and has been safely prescribed for the treatment of type 2 diabetes. In the past two decades, metformin has become the first-line drug for treating diabetes in the U.S. and other countries. However, emerging evidence indicates that metformin may hold promise in treating or preventing a multitude of medical conditions.

Overall Health Benefits of Metformin

  • Treats Diabetes Symptoms and Improves Blood Sugar Levels [1-29]
  • Promotes Weight Loss [30-48]
  • Protects Against Cancer [49-77]
  • Improves Cardiovascular Health [78-92]
  • Improves Cognitive Function [93-108]
  • Treats Polycystic Ovary Syndrome [109-124]
  • Improves Blood Pressure [125-131]
  • Fights Aging and Increases Longevity [132-169]

How Metformin Works

The mechanism behind metformin is that it increases insulin sensitivity by increasing the number of muscle and fat cell insulin receptors and the attraction for the receptor. Metformin also decreases blood sugar production in the liver and its absorption by the intestines or stomach. This in turn improves the body’s response to the effects of insulin. Scientists also believe that the guanidine compounds in metformin have potential health benefits.

Proven Health Benefits of Metformin

Treats Diabetes Symptoms and Improves Blood Sugar Levels

Combating diabetes by reducing blood sugar is the main indication of metformin. An overwhelming body of clinical trials support metformin’s beneficial effects on blood sugar levels:

  1. In a study published by the American Diabetes Association, metformin decreased blood sugar levels by 60 to 70 mg/dl in patients with non-insulin dependent type II diabetes. [1]
  2. Metformin has been shown to reduce the incidence of deaths related to diabetic complications by 30% compared to other medications for diabetes such as insulin, glibenclamide and chlorpropamide. [2]
  3. In patients with pre-diabetes, metformin administration reduced the chance of developing type 2 diabetes mellitus 31%. [3]
  4. A clinical trial found that metformin and insulin have similar safety and efficacy in the treatment of gestational diabetes. [4]
  5. In pregnant women, treatment of metformin instead of insulin was associated with less weight gain and improved neonatal outcomes. [5]
  6. In patients with type 2 diabetes and impaired glucose tolerance, the combination of metformin and lifestyle interventions delayed the progression of the disease. [6]
  7. In the Diabetes Prevention Program (DPP) trial, lifestyle intervention and metformin reduced the incidence of diabetes by 58% and 31%. [7-8]
  8. In a Chinese study, subjects with impaired glucose tolerance who received low-dose metformin (750 mg/day) produced large, significant reductions for new onset of type 2 diabetes. [9-10]
  9. A study found that metformin treatment was associated with a 40% reduction in the incidence of new-onset diabetes with an absolute risk reduction of 6% during a mean trial duration of 1.8 years. [11]
  10. In patients with impaired glucose tolerance and impaired fasting glucose, both higher and lower metformin dosage decreased rate of conversion from pre-diabetes to diabetes. [12]
  11. In patients with type 2 diabetes, early initiation of metformin is recommended as a first-line drug for monotherapy and combination therapy. [13-14]
  12. In obese patients with type 2 diabetes mellitus, metformin administration is as effective as sulfonylurea, an antidiabetic drug, in controlling blood sugar levels. [15-16]
  13. In patients sub-optimally controlled by diet and exercise, combination of metformin and insulin secretagogue reduced HbA1c (an indicator of blood sugar control) between 1.5% to 2.2%. [17-19]
  14. Combination of metformin with other antidiabetic drugs such as sulfonylureas and alpha-glucosidase inhibitors significantly reduced HbA1c. [20]
  15. Combination of metformin and the oral antidiabetic drug glimepiride in diabetic patients resulted in a lower HbA1c concentration and fewer hypoglycemic events (abnormally low blood sugar). [21]
  16. The combination of metformin and sulfonylurea was also associated with reduced all-cause mortality. [22]
  17. Metformin as added to insulin-based regimens has been shown to improve blood sugar control, and reduce body weight, hypoglycemic events, insulin requirements and total insulin dosage. [23-26]
  18. In patients with type 2 diabetes, combination of metformin and dapagliflozin reduced the incidence of hyperglycemia (high blood sugar). [27-28]
  19. The combination of saxagliptin and metformin led to clinically and statistically significant reductions in HbA1c. [29]

Promotes Weight Loss

The benefits of metformin go beyond improving blood sugar levels. Studies show that this antidiabetic drug can also benefit obese and overweight individuals by promoting weight loss:

  1. A 10-year follow-up study on obese patients with type 2 diabetes revealed reductions in body weight in the group treated with metformin compared to placebo. [30]
  2. In obese individuals with type 2 diabetes, metformin administration for 6 months caused a mean weight loss of 7 kg. [31]
  3. In the Diabetes Prevention Program (DPP) study, participants who took metformin had reduced body weight and waist circumference compared with placebo. [32]
  4. In overweight patients with type 2 diabetes, metformin treatment was associated with lesser weight gain. [33]
  5. In obese children and adolescents, metformin was associated with short-term weight loss, improvement of insulin sensitivity, and decreased visceral fat. [34]
  6. In overweight and obese patients, metformin induced weight loss by improving leptin and insulin sensitivity. [35]
  7. In clinically stable, overweight patients with chronic mental health disorder, metformin was modestly effective in reducing weight. [36]
  8. In obese insulin-resistant patients participating in a low-intensity weight-reduction program, metformin had favourable effects on body weight and body composition. [37]
  9. In overweight and obese patients, metformin treatment reduced waist-to-hip ratio. [38]
  10. In obese patients with type 2 diabetes, 700-mg dose of metformin induced weight loss by decreasing food consumption. [39]
  11. In Bahraini patients aged 20 or more, metformin treatment was associated with weight loss of 1-10 kg. [40]
  12. In elderly participants (60 years and above), metformin reduced body weight without any adverse side effects. [41]
  13. In obese, insulin-resistant adolescents, long-term treatment with metformin resulted in stabilization of body mass index (BMI) and improved body composition. [42]
  14. In patients with antipsychotic-induced weight gain, metformin treatment resulted in significant weight reduction. [43-47]
  15. In women with polycystic ovary syndrome, treatment with 850 mg of metformin twice daily for 6 months reduced weight by an average of 9.24 pounds. [48]

Protects Against Cancer

Metformin also has potent anti-cancer properties. Numerous studies show that metformin can help ward off various types of cancer:

  1. A study found that metformin users had a 55% decrease in the risk of stomach cancer compared with nonusers. [49-50]
  2. A study composed of 27 clinical trials representing more than 24,000 patients found that metformin use was associated with improved overall survival rate. [51]
  3. In diabetic patients with tumors, metformin administration was associated with a 30% reduction in overall tumour onsets. [52-53]
  4. In diabetic patients with lung cancer, pancreatic cancer and breast cancer, metformin administration was associated with better prognosis. [54-57]
  5. A cell study found that metformin inhibited tumor growth by stimulating adenosine 5′ monophosphate-activated protein kinase (AMPK). [58-59]
  6. In a breast cancer model, metformin delayed the onset of carcinoma and extended lifespan. [60]
  7. Several studies found that metformin was associated with reduced cancer incidence and mortality. [61-66]
  8. A study found that long-term metformin use was associated with reduced risk of ovarian cancer. [67-68]
  9. In diabetic patients with breast cancer, metformin treatment was associated with absence of residual invasive disease. [69-70]
  10. In Taiwanese men with type 2 diabetes mellitus, metformin use was associated with a decreased risk of incident prostate cancer. [71]
  11. In American diabetic patients, metformin use was associated with a reduced risk of colorectal cancer. [72]
  12. In diabetic patients, metformin use was associated with a reduced risk of pancreatic cancer. [73]
  13. In patients with preexisting type 2 diabetes mellitus, metformin treatment significantly reduced the risk of liver cancer by more than 80%. [74]
  14. In patients with type 2 diabetes, metformin was associated with lower cancer mortality. [75]
  15. In diabetic patients with colorectal cancer, metformin improved survival rate. [76]
  16. In female patients with type 2 diabetes, long-term metformin use was associated with reduced risk of breast cancer. [77]

Improves Cardiovascular Health

There’s also a great deal of evidence supporting the beneficial role of metformin on cardiovascular health:

  1. Metformin has been shown to prevent the fragmentation of mitochondria in endothelial cells which is associated with atherosclerosis (plaque formation). [78]
  2. In patients with heart failure, metformin administration reduced the risk of deaths by 75%. [79]
  3. A study demonstrated that metformin administration in patients with heart disease reduced the risk of heart attack, abnormal heart rhythm, and related deaths. [80]
  4. In overweight patients with type 2 diabetes, monotherapy of metformin was correlated with decreased risk of cardiovascular disease. [81]
  5. A study found that metformin may help lower the risk of cardiovascular disease by reducing the levels of free fatty acid, triglyceride, and soluble vascular cell adhesion molecule-1 (sVCAM-1). [82]
  6. In patients with type 2 diabetes, metformin treatment reduced the risk of coronary heart disease by improving cholesterol levels. [83-84]
  7. Metformin may also help combat heart disease by suppressing inflammation and coagulation. [85]
  8. In male participants, metformin treatment was associated with reduced risk of atherosclerosis (coronary artery calcium). [86]
  9. In patients with type 2 diabetes, combination of insulin and metformin reduced the risk of cardiovascular disease by 40%. [87]
  10. Metformin can help improve endothelial cell function, which involves the inner lining of the heart, by combating stress and inflammatory response. [88-89]
  11. In patients with ischaemic cardiomyopathy (weakening of heart muscle), metformin treatment was associated with reduced rates of heart attack, chest pain, and related deaths. [90]
  12. Another mechanism by which metformin improves cardiovascular health is by increasing fat redistribution. [91-92]

Improves Cognitive Function

Emerging evidence suggests that metformin may play an important role in preserving cognitive function:

  1. In the Singapore Longitudinal Aging Study, the use of metformin was associated with a 51% reduced risk of cognitive impairment. [93]
  2. A large observational study of patients with type 2 diabetes reported lower rates of dementia in metformin-treated groups compared to those treated with other antidiabetic drugs. [94]
  3. In patients with type 2 diabetes, metformin administration improved cognitive performance. [95]
  4. Metformin may help prevent Parkinson’s disease and Alzheimer’s disease by reducing the levels of abnormal protein aggregates in the brain. [96-99]
  5. Metformin exerts its neuroprotective effects via AMPK activation. [100-103]
  6. Metformin can also improve neurological deficits through various important mechanisms such as decreasing oxidative stress, preventing brain mitochondrial dysfunction, and increasing brain-derived neurotrophic factor levels. [104-107]
  7. A cell study found that metformin may help enhance spatial memory by promoting formation of new nerve cells in the brain. [108]

Treats Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a hormonal disorder caused by collection of several fluids (follicles) in the ovaries, affecting its ability to release eggs. Studies show that metformin may help treat this debilitating condition:

  1. In patients with PCOS, metformin helps reverse metabolic abnormalities including insulin resistance, hypertension, and abnormal lipid profiles. [109-110]
  2. The mechanisms by which metformin exerts its beneficial effects on PCOS is through increased insulin sensitivity, increased secretion of estrogen by the ovaries, decreased production of androgen, and enhanced production of sex hormone binding globulin. [111-112]
  3. In non-obese women with PCOS, metformin administration induced ovulation. [113-114]
  4. In women with PCOS, metformin therapy was associated with significant improvement in menstrual regularity and reduction in circulating androgen levels. [115]
  5. Metformin therapy in patients with PCOS improved ovarian steroidogenesis (production of estrogen and progesterone). [116-117]
  6. Metformin administration in women with PCOS was associated with improved ovulation, pregnancy, and live birth rates. [118]
  7. In patients with PCOS undergoing in vitro fertilization, metformin treatment improved the quality of egg and embryos. [119-120]
  8. In anovulatory women with PCOS, metformin normalized ovarian follicular development and uterine blood flow. [121]
  9. In PCOS patients, metformin administration reduced the risk of miscarriage. [122-124]

Improves Blood Pressure

The ability of metformin to improve insulin resistance and other metabolic parameters may play a part in reducing blood pressure. Studies show that metformin has potent anti-hypertensive effects:

  1. Metformin therapy in hypertensive patients reduced systolic blood pressure. [125]
  2. In obese non-diabetic subjects with no cardiovascular diseases, metformin administration significantly decreased blood pressure. [126]
  3. In non-diabetic patients, metformin effectively lowered systolic blood pressure. [127]
  4. In non-diabetic hypertensive patients, metformin treatment induced a decline in diastolic blood pressure. [128]
  5. In individuals with impaired fasting glucose, metformin treatment reduced systolic blood pressure. [129]
  6. In patients with metabolic syndrome, metformin reduced blood pressure by correcting arterial stiffness. [130]
  7. In rats, metformin attenuated salt-induced hypertension. [131]

Fights Aging and Increases Longevity

Metformin also has anti-aging benefits. According to studies, it can block or diminish various fundamental factors that accelerate the aging process:

  1. Metformin has been shown to slow the process of aging and prevent age-related diseases by protecting against DNA damage, poor mitochondrial function, and chronic inflammation. [132-136]
  2. Metformin has also been shown to increase the cellular production of mTOR and AMPK, which are longevity-promoting signaling molecules. [137-142]
  3. Animal studies have shown that metformin can increase lifespan by 20%. [143-144]
  4. A study found that diabetics taking metformin lived 15% longer than healthy non-diabetic individuals. [145]
  5. In different mouse breeds, long-term treatment with metformin extended lifespan. [146]
  6. In the United Kingdom Prospective Diabetes Study (UKPDS), metformin therapy increased life expectancy by reducing the risk of cardiovascular disease, cancer incidence, and overall mortality of diabetic patients. [147-148]
  7. Studies found that metformin can reduce the levels of reactive oxygen species (ROS), which are the major cause of aging. [149-153]
  8. A study found that metformin combats the effects of aging by suppressing inflammatory response via inhibition of nuclear factor κB (NFκB). [154-155]
  9. A cell study found that metformin exerts its anti-aging effect by preventing cellular senescence (irreversible cell cycle arrest). [156-157]
  10. In several rodent strains, adding metformin to the diet resulted in a significant increase in lifespan (14-40%). [158-161]
  11. In a model of Huntington’s disease, metformin extended lifespan by 20%. [162]
  12. In diabetic and cardiovascular disease patients, metformin increased rates of survival. [163-164]
  13. In older adults with type 2 diabetes, metformin administration may help promote longevity by preventing frailty. [165]
  14. Cell studies have shown that metformin may help combat internal aging by reducing neuronal injury and improving oxygen/glucose delivery to neurons. [166-169]

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