Metformin is generally well tolerated.[10] Common side effects include diarrhea, nausea and abdominal pain.[5] It has a low risk of causing low blood sugar.[5] High blood lactic acid level is a concern if the medication is prescribed inappropriately and in overly large doses.[11] It should not be used in those with significant liver disease or kidney problems.[5] While no clear harm comes from use during pregnancy, insulin is generally preferred for gestational diabetes.[5][12] Metformin is in the biguanide class.[5] It works by decreasing glucose production by the liver and increasing the insulin sensitivity of body tissues.[5]
The molecular mechanism of metformin is incompletely understood. Multiple potential mechanisms of action have been proposed: inhibition of the mitochondrial respiratory chain (complex I), activation of AMP-activated protein kinase (AMPK), inhibition of glucagon-induced elevation of cyclic adenosine monophosphate (cAMP) with reduced activation of protein kinase A (PKA), inhibition of mitochondrial glycerophosphate dehydrogenase, and an effect on gut microbiota.[92][93][94] Ultimately, it decreases gluconeogenesis (liver glucose production).[76] It also has an insulin-sensitizing effect with multiple actions on tissues including the liver, skeletal muscle, endothelium, adipose tissue, and the ovary.[47][95] The average patient with type 2 diabetes has three times the normal rate of gluconeogenesis; metformin treatment reduces this by over one-third.[96]
If you’re managing type 2 diabetes with metformin (Glucophage), you might be well acquainted with unwanted side effects of this drug — namely, upset stomach, diarrhea, muscle aches, and sleepiness. These can be a figurative and literal pain, but you might welcome one side effect of metformin with open arms, particularly if you’ve struggled to lose weight.
According to Watnick, the risk factors for the elderly are very similar to those for the population at large. “Those at highest risk of high blood pressure are those who suffer from obesity, those suffering from diabetes, and those with chronic kidney disease,” she explains. In fact, the risk factors for hypertension are very similar to the risks associated with high cholesterol. Any restrictions or blockages in the circulatory system negatively impact overall heart health. But the kidneys, the primary organ that regulates blood pressure, also become at risk when blood pressure rises. Severe hypertension can cause chronic kidney disease, which in turn limits the kidneys’ ability to continue regulating blood pressure. As Watnick says, “It’s a chicken or the egg thing. You can have high blood pressure which causes kidney disease. Or you can have kidney disease, and that will cause high blood pressure.” But regardless of whether hypertension is simply the result of genetic predisposition or the result of an unhealthy lifestyle, it doesn’t have to mean the end of good health.
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.
The United Kingdom's National Institute for Health and Clinical Excellence recommended in 2004 that women with PCOS and a body mass index above 25 be given metformin for anovulation and infertility when other therapies fail to produce results.[44] UK and international clinical practice guidelines do not recommend metformin as a first-line treatment[45] or do not recommend it at all, except for women with glucose intolerance.[46] The guidelines suggest clomiphene as the first medication option and emphasize lifestyle modification independently from medical treatment. Metformin treatment decreases the risk of developing type 2 diabetes mellitus in women with PCOS who exhibited impaired glucose tolerance (IGT) at baseline.[47][48]

Metformin causes depletion of Vitamin B12, Folic Acid and CoQ10, leading to feelings of tiredness, weakness and in some cases, even anemia. If you have been feeling tired all the time and are lacking the energy to do anything, you may be missing Vitamin B12, or Folic Acid (Vitamin B9), or Coenzyme Q10 (CoQ10). These nutrients are needed to ensure that red blood cells of the right size are created in the body and cells are able to produce energy.


Some side effects of metformin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
The FDA most recently revised its prescribing information on metformin in 2016.[59] Current advice is that metformin is contraindicated in people with 1) severe renal impairment (estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2); 2) known hypersensitivity to metformin; or 3) acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Warnings are also given regarding the use of metformin in less severe renal impairment, people aged 65 years old or greater, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, hepatic impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), surgery and other procedures, or in people having a radiological study with administration of an iodinated contrast agent. Metformin is recommended to be temporarily discontinued before any procedure involving use of iodinated contrast agents, (such as a contrast-enhanced CT scan or angiogram) due to the increased risk of lactic acidosis resulting from impaired renal function;[60][61] metformin can be resumed after two days after contrast administration, if renal function is adequate and stable. It is recommended that all people receiving metformin should have their renal function (eGFR) measured at least annually and more frequently in those at higher risk of developing renal impairment.
The primary symptoms of malignant hypertension is a blood pressure of 180/120 or higher and signs of organ damage. Other symptoms of malignant hypertension include bleeding and swelling of blood vessels in the retina, anxiety, nosebleeds, severe headache, and shortness of breath. Malignant hypertension may cause brain swelling, but this symptom is very rare.

In type 2 diabetes the cells in the body, particularly muscle, fat and liver cells, become resistant to the action of insulin. Insulin is the main hormone responsible for controlling the level of sugar (glucose) in the blood. It makes cells in the body remove sugar from the blood. When the cells are resistant to insulin this makes blood sugar levels rise too high.


Before measuring your blood pressure, do not smoke, drink caffeinated beverages, or exercise for at least 30 minutes before the test. Rest for at least five minutes before the measurements and sit still with your back straight and supported. Feet should be flat on the floor and not crossed. Your arm should also be supported on a flat surface like a table with the upper arm at heart level.
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Hypertension is a serious chronic disorder that can cause many harmful health effects over time. If you are an adult over the age of 20, you should have your blood pressure checked by your healthcare provide at your regular health visit. If you are over the age of 40, it's important to have your blood pressure checked annually. Remember, the reading you get from a manual machine or at the pharmacy may not be accurate.
The value of routine screening for hypertension in children over the age of 3 years is debated.[90][91] In 2004 the National High Blood Pressure Education Program recommended that children aged 3 years and older have blood pressure measurement at least once at every health care visit[89] and the National Heart, Lung, and Blood Institute and American Academy of Pediatrics made a similar recommendation.[92] However, the American Academy of Family Physicians[93] supports the view of the U.S. Preventive Services Task Force that the available evidence is insufficient to determine the balance of benefits and harms of screening for hypertension in children and adolescents who do not have symptoms.[94]
It’s no different for those reaching their senior years. While nearly one in three Americans suffers from hypertension, as high blood pressure is often called, blood pressure typically increases with age, especially once one has passed middle age. According to the National Heart, Lung,and Blood Institute, someone with healthy blood pressure at age 50 has a 90% chance of developing hypertension later in life.
Various expert groups have produced guidelines regarding how low the blood pressure target should be when a person is treated for hypertension. These groups recommend a target below the range 140–160 / 90–100 mmHg for the general population.[13][99][100][101][102] Cochrane reviews recommend similar targets for subgroups such as people with diabetes[103] and people with prior cardiovascular disease.[104]
^ Musi N, Hirshman MF, Nygren J, Svanfeldt M, Bavenholm P, Rooyackers O, Zhou G, Williamson JM, Ljunqvist O, Efendic S, Moller DE, Thorell A, Goodyear LJ (July 2002). "Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes". Diabetes. 51 (7): 2074–81. doi:10.2337/diabetes.51.7.2074. PMID 12086935.
Why stress happens and how to manage it Stress is essential for survival; the chemicals it triggers help the body prepare to face danger and cope with difficulty. Long-term stress is linked to various health conditions and can cause physical and psychological symptoms. How is it diagnosed, what types of stress are there, and how is it treated or managed? Read now
Once the diagnosis of hypertension has been made, healthcare providers should attempt to identify the underlying cause based on risk factors and other symptoms, if present. Secondary hypertension is more common in preadolescent children, with most cases caused by kidney disease. Primary or essential hypertension is more common in adolescents and has multiple risk factors, including obesity and a family history of hypertension.[83] Laboratory tests can also be performed to identify possible causes of secondary hypertension, and to determine whether hypertension has caused damage to the heart, eyes, and kidneys. Additional tests for diabetes and high cholesterol levels are usually performed because these conditions are additional risk factors for the development of heart disease and may require treatment.[6]

Metformin has been suggested as increasing production of lactate in the large intestine, which could potentially contribute to lactic acidosis in those with risk factors.[76] However, the clinical significance of this is unknown, and the risk of metformin-associated lactic acidosis is most commonly attributed to decreased hepatic uptake rather than increased intestinal production.[31][75][77]
Physical examination may include listening to the heart and lungs, feeling for pulse in the wrist and ankles, and feeling and listening to the abdomen looking for signs of an enlarged aorta. The examiner may also listen in the neck for carotid bruits (sounds made by a narrowed artery in the neck) and in the abdomen for bruits made by an abdominal aortic aneurysm.
Pre-eclampsia is a serious condition of the second half of pregnancy and following delivery characterised by increased blood pressure and the presence of protein in the urine.[23] It occurs in about 5% of pregnancies and is responsible for approximately 16% of all maternal deaths globally.[23] Pre-eclampsia also doubles the risk of death of the baby around the time of birth.[23] Usually there are no symptoms in pre-eclampsia and it is detected by routine screening. When symptoms of pre-eclampsia occur the most common are headache, visual disturbance (often "flashing lights"), vomiting, pain over the stomach, and swelling. Pre-eclampsia can occasionally progress to a life-threatening condition called eclampsia, which is a hypertensive emergency and has several serious complications including vision loss, brain swelling, seizures, kidney failure, pulmonary edema, and disseminated intravascular coagulation (a blood clotting disorder).[23][31]
Your total blood pressure reading is determined by measuring your systolic and diastolic blood pressures. Systolic blood pressure, the top number, measures the force your heart exerts on the walls of your arteries each time it beats. Diastolic blood pressure, the bottom number, measures the force your heart exerts on the walls of your arteries in between beats.
Resistant hypertension is defined as high blood pressure that remains above a target level, in spite of being prescribed three or more antihypertensive drugs simultaneously with different mechanisms of action.[131] Failing to take the prescribed drugs, is an important cause of resistant hypertension.[132] Resistant hypertension may also result from chronically high activity of the autonomic nervous system, an effect known as "neurogenic hypertension".[133] Electrical therapies that stimulate the baroreflex are being studied as an option for lowering blood pressure in people in this situation.[134]
CoQ10 depletion could cause gum problems, while depletion of Vitamins B9 and B12 could cause diarrhea, nausea and loss of appetite. A loss of appetite, nausea and diarrhea could be caused by, both, B12 and Folic Acid (B9) depletion. Since the digestive tract begins with the mouth, we must mention gingivitis or gum problems here. These can happen when CoQ10, another vital nutrient, is depleted from the body by Metformin (Biguanides).
Hypertension may not produce any symptoms, even if you have had it for years. That's why it is sometimes referred to as a "silent killer." It's estimated that 1 out of every 5 people with high blood pressure aren't aware that they have this major risk factor for strokes and heart attacks. If not properly treated, high blood pressure can damage the heart and circulation, lungs, brain, and kidneys without causing noticeable symptoms. Symptoms of high blood pressure may be present in those who have an extremely high blood pressure. Symptoms of extremely high blood pressure include the following:
Unfortunately, metformin also has one of the lowest “patient adherence” rates, because of its side effects which can appear within hours of taking your first dose. While there are actually many positive qualities about this drug compared to other diabetes medications, metformin side effects can be remarkably uncomfortable, disrupting your daily life.
Most commonly high blood pressure causes no symptoms at all. This means that people with high blood pressure can be having damage occur to their heart, kidneys, eyes, and circulation without feeling badly! It is very important, therefore, to have blood pressure testing as part of the routine physical examination. However, in people with uncomplicated high blood pressure, they may experience
If you are having surgery, including dental surgery, or any major medical procedure, tell the doctor that you are taking metformin. Also, tell your doctor if you plan to have any x-ray procedure in which dye is injected, especially if you drink or have ever drunk large amounts of alcohol or have or have had liver disease or heart failure. You may need to stop taking metformin before the procedure and wait 48 hours to restart treatment. Your doctor will tell you exactly when you should stop taking metformin and when you should start taking it again.
Vitamin B12 depletion could lead to memory and cognition issues, especially in elderly diabetics. Diabetics who have vitamin B12 depletion could suffer from confusion, memory loss, moodiness, abnormal gait, agitation, dizziness, delusions, dementia and even hallucinations. The risk of symptoms relating to a B12 deficiency increases in elderly diabetics. With age, we produce lesser stomach acid and intrinsic factor, both of which are important for digestion and absorption of Vitamin B12 from regular food sources.

Blood spots in the eyes : Blood spots in the eyes (subconjunctival hemorrhage) are more common in people with diabetes or high blood pressure, but neither condition causes the blood spots. Floaters in the eyes are also not related to high blood pressure. However, an eye doctor (ophthalmologist) may be able to detect damage to the optic nerve caused by untreated high blood pressure.   


Diabetics often complain of unexplained pain in the legs, especially calf muscles. The heart is the most important muscle in the human body and loss of CoQ10 causes a feeling of ‘heaviness’ in the heart.  Metformin causes depletion of CoQ10, which is critical for muscle energy. One of the key vitamin-like compounds that is depleted by Metformin (Biguanides) is called Coenzyme Q10 or CoQ10. It is also called ubiquinone, from the word ubiquitous, meaning everywhere. It is needed for energy production in, literally, every muscle of the human body. Depletion of this vital compound leads to lack of energy and muscle pains. Another impact of the loss of CoQ10 on cardiac health shows itself in stubborn swelling in the legs and feet.
Metformin (prescribed to treat type 2 diabetes) can cause excessive gas and bloating, heartburn, headaches, a cough, muscle pain and a metallic taste in the mouth, but these side effects typically ease after a few weeks. Very rarely, metformin may cause a serious condition called lactic acidosis. Key signs include weakness, trouble breathing, abnormal heartbeat, unusual muscle pain, stomach discomfort, lightheadedness and feeling cold. You're more at risk if you have reduced kidney function, worsening congestive heart failure or are dehydrated.
All material copyright MediResource Inc. 1996 – 2019. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/condition/getcondition/High-Blood-Pressure
Metformin was first described in the scientific literature in 1922, by Emil Werner and James Bell, as a product in the synthesis of N,N-dimethylguanidine.[108] In 1929, Slotta and Tschesche discovered its sugar-lowering action in rabbits, finding it the most potent biguanide analog they studied.[118] This result was completely forgotten, as other guanidine analogs, such as the synthalins, took over and were themselves soon overshadowed by insulin.[119]
2. How did I get the numbers? I started with the commonly seen "Systolic/ Diastolic pairs" seen in the literature - 200/120, 160/100, 140/90, 120/80 and 90/60. From there, I interpolated and extrapolated all the other numbers. Note that these are AVERAGE relationships. For instance, instead of 140/90, your BP may be 140/100, or 140/80. Each individual will have a unique systolic-diastolic relationship. If your S/D difference varies significantly from the averages shown above, this can be helpful in assessing your particular cardiovascular condition.
For older people, often the first number (systolic) is 130 or higher, but the second number (diastolic) is less than 80. This problem is called isolated systolic hypertension, which is due to age-related stiffening of the major arteries. It is the most common form of high blood pressure in older people and can lead to serious health problems (stroke, heart disease, eye problems, and kidney failure) in addition to shortness of breath during light physical activity, lightheadedness upon standing too fast, and falls. Isolated systolic hypertension is treated in the same way as regular high blood pressure (130 or higher for the first number, or 80 or higher for the second number) but may require more than one type of blood pressure medication. If your doctor determines that your systolic pressure is above a normal level for your age, ask how you can lower it.
6. Cultivate stress management. You don’t need a meta-analysis of cohort studies to prove stress can raise blood pressure, but they exist. You can’t eliminate stress, but you can minimize its impact. Research shows yoga and meditation create effective strategies to manage stress and blood pressure. If those aren’t your thing, consider other stress-relieving tactics including deep breathing or practicing mindfulness.
Hypertension is high blood pressure, a very common condition in older adults. Blood pressure is the physical force exerted by the blood as it pushes against the walls of the arteries. Blood pressure readings are written in two numbers separated by a line. The top number represents the systolic blood pressure and the bottom number represents the diastolic pressure. The systolic blood pressure is the pressure in the arteries as the heart contracts pushing the blood forward. The diastolic pressure is the pressure in the arteries as the heart relaxes.

The first chemical for hypertension, sodium thiocyanate, was used in 1900 but had many side effects and was unpopular.[152] Several other agents were developed after the Second World War, the most popular and reasonably effective of which were tetramethylammonium chloride, hexamethonium, hydralazine, and reserpine (derived from the medicinal plant Rauwolfia serpentina). None of these were well tolerated.[159][160] A major breakthrough was achieved with the discovery of the first well-tolerated orally available agents. The first was chlorothiazide, the first thiazide diuretic and developed from the antibiotic sulfanilamide, which became available in 1958.[152][161] Subsequently, beta blockers, calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers, and renin inhibitors were developed as antihypertensive agents.[158]

Arterial pressure is most commonly measured via a sphygmomanometer, which uses the height of a column of mercury, or an aneroid gauge, to reflect the blood pressure by auscultation.[1] The most common automated blood pressure measurement technique is based on the oscillometric method.[68] Fully automated oscillometric measurement has been available since 1981.[69] This principle has recently been used to measure blood pressure with a smartphone.[70] Measuring pressure invasively, by penetrating the arterial wall to take the measurement, is much less common and usually restricted to a hospital setting.
Metformin has little or no effect on body weight in type 2 diabetes compared with placebo,[28] in contrast to sulfonylureas which are associated with weight gain.[28] There is some evidence that metformin is associated with weight loss in obesity in the absence of diabetes.[29][30] Metformin has a lower risk of hypoglycemia than the sulfonylureas,[31][32] although hypoglycemia has uncommonly occurred during intense exercise, calorie deficit, or when used with other agents to lower blood glucose.[33][34] Metformin modestly reduces LDL and triglyceride levels.[31][32]

The pulse pressure is a consequence of the pulsatile nature of the cardiac output, i.e. the heartbeat. The magnitude of the pulse pressure is usually attributed to the interaction of the stroke volume of the heart, the compliance (ability to expand) of the arterial system—largely attributable to the aorta and large elastic arteries—and the resistance to flow in the arterial tree.[66]
Anyone can develop hypotension, but certain groups of people are more likely to experience it, and there are different types. For instance, orthostatic (positional) hypotension, which occurs when you stand up after sitting or lying down, is more common in older adults. Typically, “your body has certain compensatory mechanisms to prevent your blood pressure from falling when you stand up,” explains Willie Lawrence, MD, an interventional cardiologist at Research Medical Center in Kansas City, Missouri, and a spokesperson for the American Heart Association. But, he adds, “orthostatic hypotension is a problem for some people because these reflexes that should occur, don’t occur.”
All material copyright MediResource Inc. 1996 – 2019. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/condition/getcondition/High-Blood-Pressure

In the past, most attention was paid to diastolic pressure; but nowadays it is recognized that both high systolic pressure and high pulse pressure (the numerical difference between systolic and diastolic pressures) are also risk factors. In some cases, it appears that a decrease in excessive diastolic pressure can actually increase risk, due probably to the increased difference between systolic and diastolic pressures (see the article on pulse pressure). If systolic blood pressure is elevated (>140 mmHg) with a normal diastolic blood pressure (<90 mmHg), it is called "isolated systolic hypertension" and may present a health concern.[41][42]
^ Musi N, Hirshman MF, Nygren J, Svanfeldt M, Bavenholm P, Rooyackers O, Zhou G, Williamson JM, Ljunqvist O, Efendic S, Moller DE, Thorell A, Goodyear LJ (July 2002). "Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes". Diabetes. 51 (7): 2074–81. doi:10.2337/diabetes.51.7.2074. PMID 12086935.
There have been a significant number of studies on metformin’s risk of inducing lactic acidosis — a state in which lactic acid builds up in the body, which can be fatal. But the greater majority of studies concluded without any cases of lactic acidosis according to “The Phantom of Lactic Acidosis due to Metformin in Patients With Diabetes” in the American Diabetes Association’s (ADA) Diabetes Care journal.
Studies even show that blood pressure measurements outside a doctor’s office are at least as accurate as those in the office (provided the equipment works well). If your results are high, take another reading. Try, try again. If they’re still high, see your healthcare provider and get checked out. Your doctor may order blood and urine tests or an EKG to diagnose other causes for your hypertension.

In “The Blood Pressure Book: How To Get It Down and Keep It Down,” Dr. Stephen P. Fortmann compares blood pressure to a garden hose. The heart pumps blood throughout the body in a network of arteries. When those arteries become too narrow (often caused by plaque build-up from high cholesterol), the volume of blood that the arteries can handle is restricted. Like water in a narrow garden hose, narrow arteries lead to an increase in blood pressure-and high blood pressure can cause damage to artery walls and the heart itself. Damage to the circulatory system-and the complications that can result from it-is the primary reason to maintain one’s blood pressure at a healthy level.
So while metformin is often given to people with high insulin levels who have difficulty losing weight, it’s not a miracle weight loss solution, says Dr. Sood. In other words, don’t expect a dramatic change in weight if you overeat and lead a sedentary life. You must follow a sensible weight loss plan with healthy eating and physical activity to see any significant change in weight.
Blood pressure monitors for use at home can be bought at drug stores, department stores, and other places. Again, these monitors may not always give you a correct reading. You should always compare your machine’s reading with a reading from your doctor’s machine to make sure they are the same. Remember that any measurement above normal should prompt a visit to the doctor, who can then talk with you about the best course of action.

Lactate uptake by the liver is diminished with metformin use because lactate is a substrate for hepatic gluconeogenesis, a process that metformin inhibits. In healthy individuals, this slight excess is cleared by other mechanisms (including uptake by unimpaired kidneys), and no significant elevation in blood levels of lactate occurs.[31] Given severely-impaired kidney function, clearance of metformin and lactate is reduced, increasing levels of both, and possibly causing lactic acid buildup. Because metformin decreases liver uptake of lactate, any condition that may precipitate lactic acidosis is a contraindication. Common causes include alcoholism (due to depletion of NAD+ stores), heart failure and respiratory disease (due to inadequate tissue oxygenation); the most common cause is kidney disease.[75]
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