The Potential Benefits Of Metformin Beyond Managing Type 2 Diabetes
More and more research suggests that the benefits of this medication arent reserved for people with type 2 diabetes. Griebeler says that even though metformin is only approved for the treatment of type 2 diabetes, its being used off-label to treat weight reduction, polycystic ovarian syndrome , infertility, prevention of diabetes, prevention of pregnancy complications, and obesity.
Its been shown to have a positive effect on the following health issues for people without diabetes:
Osteoarthritis According to a study published in May 2019 in Arthritis Research and Therapy, metformin can help people with obesity and osteoarthritis. The researchers found that metformin helped people lose cartilage at a lower rate than those who did not take metformin, and they observed that the medication reduced participants risk of needing a total knee replacement, which is a possible complication of this health condition.
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Alzheimers Disease A study published in April 2017 in Alzheimer Disease and Associated Disorders involving 20 people without type 2 diabetes found that metformin improved executive function skills, learning, memory, and attention. The randomized, controlled trial was short and small , though, so more research is needed.
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Metformin And A Decreased Incidence Of Cancer
Diabetes has been associated with an enhanced risk for the development of various cancers . A retrospective study published in 2005 reported that patients with diabetes who had been treated with metformin for T2DM had a lower risk of cancer and highlighted the possible link between metformin and the serine-threonine tumor suppressor, LKB1, as a mechanism for the reduced risk . Similarly, the link between metformin and the activation of AMPK has been emphasized as the basis for the anti-proliferative effects of metformin .
Extensive support for a protective effect of metformin against cancer has been provided by numerous, but not all studies . For instance, no association has been shown between the use of metformin and a lower incidence of bladder cancer and concerns have also been expressed how data from observational studies are analyzed . The National Cancer Institute lists a number of on-going clinical trials involving metformin for the following: Her2 positive breast cancer, head and neck squamous cell cancer, endometrial and ovarian cancers, multiple myeloma, lymphocytic leukemia, and thyroid cancer. Examples include a Phase II study, NCT02028221, designed to determine whether metformin reduces obesity-associated breast cancer risk and due to be completed in mid-2021. A Phase III trial, NCT01101438, Metformin Versus Placebo on Recurrence and Survival in Early Stage Breast Cancer is due to be completed in early 2022.
Metformin And Lactic Acidosis
Concentrations of lactate in the blood are normally stable, as production and consumption are equivalent . As mentioned, one of the major effects of metformin is to increase lactate production , mainly by the gut wall. Since, in normal conditions, lactate clearance is proportional to its concentration, the increase in lactate during metformin treatment is usually minimal . Severe hyperlactatemia thus occurs mainly when clearance decreases, leading to lactic acidosis. When occurring during metformin treatment , lactic acidosis is classified as a type B, as it develops when clearance of lactic acid by oxidation or gluconeogenesis is impaired, although it can present with features of type A and as such hypoxemia should be considered a contraindication for its use.
Metformin is not metabolized and is eliminated unchanged primarily by the kidney . Metformin clearance therefore depends only on renal function and, when filtration is severely reduced, it accumulates in the plasma. The actual level of concentration of plasma metformin at which the risk of MALA increases remains a matter of debate. With the recommended dose and schedules, metformin concentrations are usually < 1 mg/L and rarely exceed 5 mg/L only persistent levels above this value seem to increase the risk of MALA . More recently, in metformin-treated patients admitted in an emergency context, plasma metformin concentrations 9.9 mg/L were strongly associated with the presence of lactic acidosis .
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Metformin And Hiv Lypodystrofy
Antiretroviral therapy has been associated with an increased prevalence of type 2 diabetes mellitus and insulin resistance among HIV-infected patients . Lipodystrophy, characterized by morphological and metabolic changes , is highly prevalent in patients on highly active antiretroviral therapy , occurring in 40% to 80% of patients .
Nucleoside reverse transcriptase inhibitors , particularly thymidine analogues , have been associated with morphological changes, particularly extremity fat loss , while protease inhibitors have been associated with biochemical derangements of glucose and lipids as well as with localized accumulation of fat .
Lifestyle modifications such as diet and exercise and switching antiretroviral therapies seems to be of limited value in reducing visceral abdominal fat . Metformin has been shown to reduce VAT but at the expense of accelerating peripheral fat loss . Favorable effects on insulin levels , insulin sensitivity , weight , flow-mediated vasodilation , and lipid profiles have also been described.
Drug Interactions Of Metformin
To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs youre taking. Talk to your healthcare provider to find out how metformin might interact with something else you are taking.
The dose of metformin varies depending on what it is being used to treat, the age of the patient, and any previous health conditions or factors that could potentially interfere with or amplify the drugs effect. There are a host of medications thought to theoretically decrease metformin effectiveness , but most are thought not to do so in a clinically significant manner .
Below are some exceptions.
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The Connection Between Metformin And Improved Neurological Function
Diabetes-associated hyperglycemia, hyperinsulinemia, elevated oxidative stress, vascular disease, and inflammation are all linked to cognitive decline and, as reflected by a meta-analysis, it was concluded that metformin reduces cognitive decline and dementia in T2DM subjects .
In the Singapore Longitudinal Aging Study 2,365 subjects with diabetes were monitored for 4 years see Table 2 . In a cross-sectional and longitudinal multivariate analysis, odds ratios of association of the chronic use of metformin with cognitive disability were evaluated demonstrating a substantial inverse relationship with cognitive impairment . In a large observational study, 67,731 participants, who had no evidence of dementia, were non-diabetic, and aged 65 were followed from January 2004 to December 2009, to observe the onset of T2DM and compare the risk of the incidence of dementia associated with the use of anti-diabetic drugs and reported that metformin reduced the risk of developing dementia . In another clinical trial, 58 participants who had both depression and T2DM received either metformin or placebo for 24 weeks concluded that metformin improved cognitive performance .
The Effect Of Metformin On Pet Imaging
As well as the effect of metformin on AMPK and thus on tumour proliferation, it seems that this drug may show anti-cancer activity also through its effect on insulin levels. In a study using murine colorectal cancer cells, exposition to metformin had no effect on the insulin level or FDG uptake by tumour cells in normoinsulinaemic mice, but a decrease of insulin levels and FDG uptake in mice with baseline hyperinsulinaemia was found. The authors suggest that the above effect of metformin use should be taken into consideration in the evaluation of its anticancer activity because the response may depend on whether we have a patient with hyperinsulinaemia and an insulin-sensitive tumour or not . Further improvement of understanding of the effect of metformin on FDG uptake and PET image interpretation is necessary. Furthermore, based on the information presented above, a question arises whether FDG is an appropriate marker in the assessment of anticancer activity of metformin .
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Metformin Compared With Other Antidiabetic Medications
Compared toinsulin and sulfonylureas , metformin shows a lower incidence of weight gain and fewer instances of critically lowered blood sugar .
Rosiglitazone is more effective than both metformin and sulfonylurea in the delay of type 2 diabetes onset but has more adverse side effects than metformin .
A review of 347 human studies indicated that metformin did not pose a higher risk of lactic acidosis in comparison to other treatments for diabetes or placebo. However, this study did not take into account patients at a specially high risk of the condition .
Diabetic patients taking either metformin or sulfonylureas have a similar risk of developing cancer .
Sulfonylureas can increase the risk of Parkinsons disease in patients with type 2 diabetes. This effect is often neutralized by the addition of metformin to the treatment .
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Pharmacokinetic Properties Of Metformin
It is important that results from in vitro studies using high micromolar and millimolar concentrations of metformin, often for long-exposure times, are looked at critically as such data may not be readily translated to effects when used in humans. A useful comparison of the doses of metformin used therapeutically versus pre-clinical studies was made by Badrick and Renehan, indicating that for pre-clinical studies done in vivo, the doses ranged from x2 to x45 therapeutic doses and that for studies done in vitro, concentrations ranged from x25 to x1000 higher than those observed in patients .
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Will My Doctor Prescribe Metformin For Weight Loss
If you have type 2 diabetes or prediabetes and are overweight or obese, your doctor may prescribe metformin to help you manage your diabetes or lower your risk of diabetes, and to see if it can help you to lose weight. In fact, your doctor might prescribe metformin for weight loss even if you dont have diabetes or prediabetes.
This use of metformin is called an off-label use. That means that the FDA has not approved metformin as a weight-loss aid. As a result, there is less information about how effective it is for this purpose.
Where Can I Find Diabetes Relief
While there are prescription drugs for diabetes, absolutely nothing rather does the job totally. Thanks to recent advancements in clinical studies & research study conducted at specialized diabetes centers throughout the nations, theres a brand-new solution to speed up the results & relief youre looking for.
Through the research done by our authors, one extra measure worth considering is natural supplements. Normally speaking, natural supplements have actually existed for countless years with amazing results and have started to make a huge return over the last few years. Whats the natural supplement perfect for quickly supporting diabetes? Let us introduce Glucofort.
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What Are Warnings And Precautions For Metformin
Warnings
Metformin has moderate interactions with at least 74 different drugs.
Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.
Contraindications
Contraindication includes hypersensitivity, chronicheart failure, metabolic acidosis with or without coma, diabetic ketoacidosis , severe renal disease, abnormal creatinine clearance resulting from shock, , or myocardial infarction and lactation.
Effects of Drug Abuse
There are no effects of drug abuse from the use of metformin.
Short-Term Effects
There are no short-term effects from the use of metformin.
Long-Term Effects
There are no long-term effects from the use of metformin.
Cautions
Use with caution in patients with congestive heart failure, fever, trauma, surgery, the elderly, renal impairment, or hepatic impairment.
Instruct patients to avoid heavy alcohol use.
Suspend therapy prior to any type of surgery.
Rare, but serious, lactic acidosis can occur due to accumulation.
Possible increased risk of cardiovascular mortality.
May cause ovulation in anovulatory and premenopausal polycystic ovary syndrome patients.
It may be necessary to discontinue therapy with metformin and administer insulin if patient is exposed to stress .
Ethanol may potentiate metformin’s effect on lactate metabolism.
May impair vitamin B12 or calcium intake/absorption monitor B12serum concentrations periodically with long-term therapy.
Iodinated contrast imaging procedures.
Insulin Resistance And Metabolic Syndrome
Insulin resistance means the absence of appropriate response of the body to insulin. Insulin resistance may precede development of type 2 diabetes by many years. This is a condition where both endogenous and exogenous insulin do not have an appropriate effect on glucose uptake and utilisation, as they would in healthy people.
Insulin resistance may also be of secondary nature and it may occur in the course of such conditions as: liver cirrhosis, cancers, autoaggressive diseases, uraemia, and endocrinopathies: Cushing syndrome, acromegaly, or pheochromocytoma .
Not only an excess but also a deficit of fatty tissue leads to insulin resistance, which is observable in lipodystrophy syndromes. In these conditions metformin is also used .
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Side Effects Of Metformin
The most common side effects of metformin are related to gut complications and include upset stomach, nausea, vomiting, diarrhea, lightheadedness, or a metallic taste in the mouth .
In general, older patients may be at an increased risk for some of its side effects, such as lactic acidosis or low blood sugar, due to other factors .
However, other more severe side effects should be taken into account. Consult your doctor if these effects are severe or mild but persistent and carefully follow their recommendations.
Potential Benefit To People With Diabetes
Knowing more about how salicylate works could help scientists understand exactly how the drug could benefit people with type 2 diabetes. This will be an important step towards clinical trials testing the drug and ultimately making it available the diabetes clinic.
This could mean people with type 2 diabetes who dont benefit from, or cant take, metformin could access an alternative treatment, to help slow the progression of their diabetes and protect against complications.
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What Exactly Is Glucofort
Glucofort is founded by Andrew Freeman, 50, whose story that led to a transformation within the diabetes neighborhood. He is practicing psychologist who, when informed of his type 2 diabetes medical diagnosis, could not believe what he heard, specifically knowing how cautious he had been with his health.
He decided to utilize his experience & connections to establish a viable solution that is safe yet efficient. After countless hours of research study, Andrew claims to have actually discovered the diabetes-reversing secret lost in eastern Asia.
Glucoforts blood sugar assistance, permitted by what Freeman discovered, works by increasing insulin production while decreasing its resistance into your cells. It also supports healthy glucose metabolic process. The formula in this natural supplement only enables needed glucose to be stored in the body and burns the rest by transforming it into energy.
In addition, Glucofort supports cardiovascular health and helps in reducing the opportunities of heart-related illness on top of being utilized to help treat type-2 diabetes. Plus, no major way of life modifications are needed! No more stressing about rigorous dieting plans or extensive workouts to benefit from the advantages.
You can also expect it to assist in weight-loss because of the ingredients balancing blood sugar levels, which is the first step to manage weight.
What Other Information Should I Know
Your doctor will tell you how to check your response to this medication by measuring your blood sugar levels at home. Follow these instructions carefully.
If you are taking the extended-release tablets, you may notice something that looks like a tablet in your stool. This is just the empty tablet shell, and this does not mean that you did not get your complete dose of medication.
You should always wear a diabetic identification bracelet to be sure you get proper treatment in an emergency.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
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Effects On Body Weight
Metformin may have a neutral effect on body weight of patients with T2DM when compared to diet or may limit or decrease the weight gain experienced with sulfonylureas , TDZ , insulin , HAART , and antipsychotics drugs .
Modest weight loss with metformin has been observed in subjects with IGT . However, a meta-analysis of overweight and obese non-diabetic subjects, found no significant weight loss as either a primary or as secondary outcome .
The mechanisms by which metformin contributes to weight loss may be explained through the reduction in gastrointestinal absorption of carbohydrates and insulin resistance , reduction of leptin and ghrelin levels after glucose overload , and by induction of a lipolitic and anoretic effect by acting on glucagonlike peptide 1 .
Are There Alternatives To Metformin
Usually, metformin is the first choice of medicine prescribed by doctors for type 2 diabetes when lifestyle changes of diet and exercise have failed. If metformin no longer works well enough on its own, your doctor may add another diabetes medicine to metformin. But if metformin is not suitable for you, your doctor may prescribe you another diabetes medicine altogether.
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Metformin And Hyperglycemic Memory
Hyperglycemic memory was first described in humans as the resistance to preventing the development of diabetic retinopathy despite achieving good glycemic control in patients . Hyperglycemic memory contributes to the pathophysiology of diabetes despite the initiation of intensive glycemic control . Data from studies of tissues from streptozotocin-induced diabetic rats and also of endothelial cells in culture indicate that glucose-elevated fibronectin expression is not reversed when normal glycaemia is restored .
Metformin has been shown to reverse hyperglycemic memory. In bovine retinal capillary endothelial cells and retinas from diabetic rats, hyperglycemia-induced elevated levels of NF-B, and Bax, a pro-apoptotic gene, were sustained even after returning to normoglycemia . BRECs where SIRT1 was knocked down with siRNA knockdown demonstrated an increased sensitivity to hyperglycemic stress, whereas SIRT1 overexpression, or exposure to metformin, inhibited the increase of mitochondrial ROS by upregulation of LKB1, and suppressed the expression of NF-B and the apoptosis regulator protein, Bax . Several other studies using a variety of different cell types have reported that metformin inhibits NF-B activation, decreases the production of inflammatory cytokines and the genes that code for the inflammatory response thus supporting the healthspan benefits of metformin .