Weight Watchers Review
No progress as US, Cuba meet on mysterious 'health attacks' Cuba said Thursday the United States is continuing to withhold important information that could help in the investigation into mysterious incidents And while she does have some help from her team, Kate is known for choosing and doing much of her anti-aging herself including for her own wedding day! Archived from the original on 3 August Meanwhile, consumers may weigh in a lot sooner. Not a good match.
Latest Health Headlines
Metformin has also been reported to decrease the blood levels of thyroid-stimulating hormone in people with hypothyroidism. In a clinical trial of subjects, Gastrointestinal upset can cause severe discomfort; it is most common when metformin is first administered, or when the dose is increased. The discomfort can often be avoided by beginning at a low dose 1. Long-term use of metformin has been associated with increased homocysteine levels  and malabsorption of vitamin B The most serious potential adverse effect of biguanide use is metformin-associated lactic acidosis MALA.
Though the incidence for MALA is about nine per , person-years,  this is similar to the background incidence of lactic acidosis in the general population. A systematic review concluded no data exists to definitively link metformin to lactic acidosis. Phenformin , another biguanide, was withdrawn from the market because of an increased risk of lactic acidosis rate of per , patient-years. Lactate uptake by the liver is diminished with metformin administration 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. Because metformin decreases liver uptake of lactate, any condition that may precipitate lactic acidosis is a contraindication. 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.
Lactic acidosis is initially treated with sodium bicarbonate , although high doses are not recommended, as this may increase intracellular acidosis. A review of metformin overdoses reported to poison control centers over a five-year period found serious adverse events were rare, though the elderly appeared to be at greater risk.
The most common symptoms following overdose include vomiting, diarrhea , abdominal pain, tachycardia , drowsiness, and, rarely, hypoglycemia or hyperglycemia. Extracorporeal treatments are recommended in severe overdoses. Metformin may be quantified in blood, plasma, or serum to monitor therapy, confirm a diagnosis of poisoning, or assist in a forensic death investigation. Chromatographic techniques are commonly employed. The H 2 -receptor antagonist cimetidine causes an increase in the plasma concentration of metformin by reducing clearance of metformin by the kidneys;  both metformin and cimetidine are cleared from the body by tubular secretion , and both, particularly the cationic positively charged form of cimetidine, may compete for the same transport mechanism.
Metformin also interacts with anticholinergic medications, due to their effect on gastric motility. Anticholinergic drugs reduce gastric motility, prolonging the time drugs spend in the gastrointestinal tract.
This impairment may lead to more metformin being absorbed than without the presence of an anticholinergic drug, thereby increasing the concentration of metformin in the plasma and increasing the risk for adverse effects.
Metformin's main effect is to decrease liver glucose production. Metformin decreases high blood sugar , primarily by suppressing liver glucose production hepatic gluconeogenesis. Multiple potential mechanisms of action have been proposed, including; 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.
Activation of AMPK was required for metformin's inhibitory effect on liver glucose production. In addition to suppressing hepatic glucose production, metformin increases insulin sensitivity, enhances peripheral glucose uptake by inducing the phosphorylation of GLUT4 enhancer factor , decreases insulin-induced suppression of fatty acid oxidation ,  and decreases absorption of glucose from the gastrointestinal tract.
Increased peripheral use of glucose may be due to improved insulin binding to insulin receptors. AMPK probably also plays a role in increased peripheral insulin sensitivity, as metformin administration increases AMPK activity in skeletal muscle.
The usual synthesis of metformin, originally described in , involves the one-pot reaction of dimethylamine hydrochloride and 2-cyanoguanidine over heat. According to the procedure described in the Aron patent,  and the Pharmaceutical Manufacturing Encyclopedia ,  equimolar amounts of dimethylamine and 2-cyanoguanidine are dissolved in toluene with cooling to make a concentrated solution, and an equimolar amount of hydrogen chloride is slowly added.
Steady state is usually reached in one or two days. Metformin has acid dissociation constant values pKa of 2. The metformin pKa values make metformin a stronger base than most other basic medications with less than 0. Furthermore, the lipid solubility of the nonionized species is slight as shown by its low logP value log 10 of the distribution coefficient of the nonionized form between octanol and water of These chemical parameters indicate low lipophilicity and, consequently, rapid passive diffusion of metformin through cell membranes is unlikely.
As a result of its low lipid solubility it requires the transporter SLC22A1 in order for it to enter cells. More lipophilic derivatives of metformin are presently under investigation with the aim of producing prodrugs with superior oral absorption than metformin. Metformin is not metabolized. It is cleared from the body by tubular secretion and excreted unchanged in the urine; metformin is undetectable in blood plasma within 24 hours of a single oral dose.
The biguanide class of antidiabetic medications, which also includes the withdrawn agents phenformin and buformin , originates from the French lilac or goat's rue Galega officinalis , a plant used in folk medicine for several centuries. Metformin was first described in the scientific literature in , by Emil Werner and James Bell, as a product in the synthesis of N , N -dimethylguanidine.
Interest in metformin resumed at the end of the s. In , metformin, unlike some other similar compounds, was found not to decrease blood pressure and heart rate in animals. Garcia  used metformin he named it Fluamine to treat influenza; he noted the medication "lowered the blood sugar to minimum physiological limit" and was not toxic.
Garcia believed metformin to have bacteriostatic , antiviral , antimalarial , antipyretic and analgesic actions. Instead he observed antiviral effects in humans.
French diabetologist Jean Sterne studied the antihyperglycemic properties of galegine , an alkaloid isolated from Galega officinalis , which is related in structure to metformin and had seen brief use as an antidiabetic before the synthalins were developed.
Sterne was the first to try metformin on humans for the treatment of diabetes; he coined the name "Glucophage" glucose eater for the medication and published his results in Metformin became available in the British National Formulary in It was sold in the UK by a small Aron subsidiary called Rona.
Broad interest in metformin was not rekindled until the withdrawal of the other biguanides in the s. Metformin was approved in Canada in ,  but did not receive approval by the U. Liquid metformin is sold under the name Riomet in India. Metformin IR immediate release is available in , , and mg tablets. All of these are available as generic medications in the U. Metformin SR slow release or XR extended release was introduced in It is available in , , and mg strengths, mainly to counteract common gastrointestinal side effects, as well as to increase compliance by reducing pill burden.
No difference in effectiveness exists between the two preparations. When used for type 2 diabetes, metformin is often prescribed in combination with other medications. Several are available as fixed-dose combinations , to reduce pill burden and simplify administration.
A combination of metformin and rosiglitazone was released in and sold as Avandamet by GlaxoSmithKline. By it had become the most popular metformin combination. In , the stock of Avandamet was removed from the market, after inspections showed the factory where it was produced was violating good manufacturing practices.
However, following a meta-analysis in that linked the medication's use to an increased risk of heart attack ,  concerns were raised over the safety of medicines containing rosiglitazone. In September the European Medicines Agency EMA recommended that the medication be suspended from the European market because the benefits of rosiglitazone no longer outweighed the risks.
In November , the FDA lifted its earlier restrictions on rosiglitazone after reviewing the results of the RECORD clinical trial a six-year, open label randomized control trial , which failed to show elevated risk of heart attack or death associated with the medication. Dipeptidyl peptidase-4 inhibitors inhibit dipeptidyl peptidase-4 and thus reduce glucagon and blood glucose levels. In Europe, Canada, and elsewhere metformin combined with linagliptin is marketed under the trade name Jentadueto.
Sulfonylureas act by increasing insulin release from the beta cells in the pancreas. Metformin is available combined with the sulfonylureas glipizide Metaglip and glibenclamide US: Meglitinides are similar to sulfonylureas. The combination of metformin with pioglitazone and glibenclamide  is available in India as Triformin. From Wikipedia, the free encyclopedia. B No risk in non-human studies. S4 Prescription only CA: Pharmacy and pharmacology portal Medicine portal.
Clinical Pharmacology and Therapeutics. A review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus". Archived from the original on 24 December Retrieved 2 January A Systematic Review and Meta-analysis". Annals of Internal Medicine. Archived from the original on Archived PDF from the original on First choice for monotherapy: Analogue-based Drug Discovery II. Herb, nutrient, and drug interactions: Archived PDF from the original on 13 December Retrieved 8 December Archived from the original on 3 August Retrieved 11 January Blake; Stanifer, John W.
Diab Vasc Dis Res. International Journal of Obesity. The Cochrane Database of Systematic Reviews. Current Medical Diagnosis and Treatment 49th ed. Bristol-Myers Squibb Company; Fat chance of those two paying off what they owe me.
I am hassled to death for payment, and another man is using my information, and his wife has my first name! I cannot seem to stop him! It makes me so damn mad. But my credit with the utility companies, like phone, electric, and cable and other such companies is excellent. I pay my rent on time, and have an excellent rental record!! But my credit history?
I have a credit score of or something like that—it really sucks! I think credit cards are from Satan. At one time when I had an excellent job, I had more than seven credit cards, enough credit to charge up to half a million dollars—no balances on them. I would just use them, pay them off each month!
I had great credit. Then I went to college—wow! After my identity was stolen—my credit has never recovered! Even with a fraud alert—Fred Meyer still allowed some idiot to open an account using my information, and only when I could finally prove by demonstrating this person did not know my parents—or have their correct information—did they finally terminate the fraudulent account!
Thank God I now do banking at a small institution that knows my history—knows me by my first name, and has my accounts all marked. Anything funny happens, my accounts are frozen—and I am called immediately. It can be a hassle, but better than losing my bank accounts to strangers. Good luck to all of you out there. I will only carry or use a Debit Card—and with the restriction that my bank will not pay any overages.
NO money in the account—the card is useless! This IS the cheapest way to do banking, and no fees, no charges, no interest, and pain. Sign me, burned, but good in credit land. I have two cards that will soon roll into annual fee period, if I close them out after applying for one of the 7 best cards will my credit rating suffer. I opened them about this time last year to improve my credit score. I owe nothing on them now but afraid to close out. There are 7 different cards.
Capital One Secured Mastercard; 2: Barclaycard Rewards Mastercard; 3: Capital One Spark Cash for Business. This article has only named 6 cards yet advertised as the 7 best cards for less than perfect credit. Please revamp article or headline because false advertising is a crime. I totally agree with you! Then when they get in a classroom or are typing things on here , they seem weird and stupid. I guess there are exceptions.
Karen is absolutely right about First Premier I stirred up an old debt to them trying to clean up my credit…. Why are many of the people responding to this so weird and stupid? So much bad grammar, horrendous spelling, and just bad writing in general. Has the internet caused this or is the population just that illiterate?
These responses are not provided or commissioned by the credit card issuer. Responses have not been reviewed, approved or otherwise endorsed by the credit card issuer. Tasha has been working in Silicon Valley for the past 20 years, enjoying a long-lived career in Product Management and Marketing.
Credit Cards Credit Monitoring.