METFORMIN - SCIENCE & RESEARCH
Oral diabetes medicine that helps control blood sugar levels
FDA approved drug to treat diabetes
A pill, derived from natural compounds in the French Lilac plant
Used successfully for over 60 years with an outstanding safety record
On the World Health Organization’s Model List of Essential Medicines, a catalog of the most effective, safe, and cost-effective therapies
Background & History
Lowers risk of colon & pancreatic cancer
Reduces risk of cognitive impairment
Lowers rate of dementia
Reduces risk of macrovascular disease
Provides weight loss in some patients
Reduces chances of diabetes
Note: Metformin has not been approved by FDA for these uses, but there are multiple studies that have shown these benefits, see below. Learn more about "of label" uses
How it works on a cellular level in relation to aging
For an organism to survive, there has to be a balance between the anabolic processes which generate energy, and catabolic processes that use this energy for fuel. The balance is especially important when energy intake is low and cells don’t have an adequate supply to meet the demand. In such cases, organisms avoid crisis by implementing biological austerity measures, reallocating limited resources from growth and reproduction to self-preservation and survival. Significantly, organisms in this “thrifty” state show remarkable resistance to multiple age-onset pathologies.
Metformin delivers this effect by limiting metabolic reactions in mitochondria, thereby slowing down the process by which our cellular powerhouses convert macronutrients to energy. This results in less ATP production, which in turn activates AMPK, an enzyme that senses when a cell has low energy levels. When low levels are detected, AMPK activates multiple pathways to implement biology austerity measures, promoting several energy production benefits, including:
Glucose uptake (Shaw 2005)
Increased insulin sensitivity and thus decreased insulin levels
Fatty acid uptake
Induced fatty acid oxidation
Decreased IGF-1 signaling ((Liu et al., 2011)
Reduction in chronic inflammation (Saisho, 2015)
Reduction in accumulation of oxidative damage
Switches off energy-consuming processes
Slows down rate of DNA damage (Algire et al., 2012)
AGING PATHWAYS IMPACTED
In 2013 a team of researchers broke down the causes of aging into 9 distinct scientific "hallmarks" (Aging Pathways) and explained how these interact with each other to drive the onset of age-related diseases.
Hallmarks Impacted by Metformin
Deregulated Nutrient Sensing
9 Hallmarks of Aging
Loss of Proteostasis
Deregulated Nutrient Sensing
Stem Cell Exhaustion
Altered Intercellular Communication
RESEARCH & STUDIES
Can People with Type 2 Diabetes Live Longer Than Those Without?
Surprisingly, yes they can, if they are treating it with metformin. This was the finding of a study of 78k people with type 2 diabetes, compared to a control group of 78k people without diabetic controls. Patients with type 2 diabetes who were taking Metformin had longer survival than did non-diabetic control matches.
A retrospective study of 62k patients in UK: “Metformin use was associated with lower risk of cancer of the colon or pancreas..."
A representative population study of 800k individuals: "Metformin can reduce the incidences of several gastroenterological cancers..."
A study conducted at M.D. Anderson Cancer Center involving 973 patients and 863 controls: "Metformin use was associated with reduced risk of pancreatic cancer..."
A retrospective study of 3,800 men conducted in Ontario, Canada: "Increased cumulative duration of metformin exposure after Prostate Cancer diagnosis was associated with decreases in both all-cause and Prostate Cancer-specific mortality..."
A study involving 1,300 patients in Netherlands: "Metformin use was associated with lower cancer mortality compared with non users..."
A case-control study of 450K US veterans who underwent colonoscopy between 1999 and 2014: "Metformin was associated with a 14% statistically significant reduced rectal cancer odds ..."
Metformin is Associated with a Higher Cancer Survival Rate
A Mayo Clinic study evaluated the association between metformin and the prognosis in ovarian cancer across 240 women (60 cases and 178 controls). Study had a heavy emphasis on the survival comparisons between diabetic women who had ovarian cancer and took metformin (cases) and non-diabetic women who had ovarian cancer (controls). "The results from our study demonstrate that metformin intake independently predicts better survival in patients with ovarian cancer."
A study of 27 ovaries showed that scarring of the ovaries occurs with age and metformin maybe able to halt that process: "Metformin abrogates age-associated ovarian fibrosis..."
Ovarian Cancer is the 5th most common cancer in women, and the deadlest with a mortality rate of 65%
Diabetic women who took metformin had better survival than nondiabetic women who did not take metformin.
Metformin is Associated with a Higher Ovarian Cancer Survival Rate
Source: Mayo Clinic Study, Dec 2012
A study of 365 people aged 55 and over, who were followed for 4 years: "Controlling for age, education, diabetes duration, fasting blood glucose, vascular and non-vascular risk factors, Metformin use showed a significant inverse association with cognitive impairment."
A study of 67,731 participants who were non-demented, non-diabetic, aged 65 or over at baseline, from January 2004 to December 2009: "Diabetes is associated with an increased risk of dementia. The risk effect becomes weaker provided that participants take sulfonylureas or Metformin rather than thiazolidinediones for a longer period"
A diabetes Prevention Program Group study showed that lifestyle intervention or metformin significantly reduced diabetes development over 15 years. "At year 15, the cumulative incidences of diabetes were 55% in the lifestyle group, 56% in the metformin group, and 62% in the placebo group."
Source: Diabetes Prevention Program
Metformin Delays and Prevents Diabetes Development
A study of 390 patients in a randomized, placebo-controlled trial with a follow-up period of 4.3 years: "Metformin did, however, reduce the risk of macrovascular disease after a follow-up period of 4.3 years..."
A study of 154 patients over a 6 month period in Germany: "Metformin is an effective drug to reduce weight in a naturalistic outpatient setting in insulin sensitive and insulin resistant overweight and obese patients..."
SAFETY & SIDE EFFECTS
Most Common side effects of metformin:
Gastrointestinal discomfort (diarrhea, nausea, bloating)
Reduction of Vitamin B12 levels, please supplement Vitamin B12
Most people start with a small dose to avoid stomach discomfort (½ or 1 tablet per day with food, increasing to what has been prescribed on the bottle). We commonly use the extended release (ER) version of metformin to reduce stomach discomfort.
Note: Metformin is commonly stopped a week before any surgical procedure or medical diagnostic requiring contrast, such as a CT scan. If you are not sure if you need to stop metformin, please ask the doctor ordering the test or procedure.
For a full list of possible side effects Click Here
Tell your doctor and pharmacist if you are allergic to metformin, any of the ingredients of metformin liquid or tablets, or any other medications. Ask your pharmacist or check the manufacturer's patient information for a list of the ingredients.
Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention any of the following: amiloride (Midamor); angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), captopril, enalapril (Vasotec, in Vaseretic), fosinopril, lisinopril (in Zestoretic), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik); beta-blockers such as atenolol (Tenormin), labetalol (Trandate), metoprolol (Lopressor, Toprol XL), nadolol (Corgard, in Corzide), and propranolol (Hemangeol, Inderal, InnoPran); calcium channel blockers such as amlodipine (Norvasc), diltiazem (Cardizem, Cartia, Diltzac, others), felodipine, isradipine, nicardipine (Cardene), nifedipine (Adalat, Afeditab CR, Procardia), nimodipine (Nymalize), nisoldipine (Sular), and verapamil (Calan, Covera, Verelan, in Tarka); cimetidine (Tagamet); digoxin (Lanoxin); diuretics ('water pills'); furosemide (Lasix); hormone replacement therapy; insulin or other medications for diabetes; isoniazid (Laniazid, in Rifamate, in Rifater); medications for asthma and colds; medications for mental illness and nausea; medications for thyroid disease; morphine (MS Contin, others); niacin; oral contraceptives ('birth control pills'); oral steroids such as dexamethasone, methylprednisolone (Medrol), and prednisone (Rayos); phenytoin (Dilantin, Phenytek); procainamide; quinidine (in Nuedexta); quinine; ranitidine (Zantac); triamterene (Dyrenium, in Maxzide, others); trimethoprim (Primsol); or vancomycin (Vancocin). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
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* Prescription products require an online consultation with a physician who will determine if a prescription is appropriate. See above for important safety information. Benefits outlined on agelessrx.com are based on 3rd party studies. Metformin is offered as a subscription service you can cancel at any time.