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Metformin Response

GLUT2 regulates how glucose moves among liver, blood and kidneys. Patients with the variant had less of this glucose transporter gene, hampering the liver’s ability to process blood glucose. Metformin reverse this effect.
Researchers found that the variant was also linked to higher body weight, which might explain the observation that Metformin works best on overweight patients. For some patients, the effect is profound that they respond as if they were taking a double dose of Metformin.
Metformin is often used as first-line therapy for this disorder given that it is cheap, may cause weight loss and does not have significant side-effects in healthy patients. On the other hand, as many as one third of all patients with type 2 diabetes initially treated with Metformin never achieve a meaningful response to this intervention. Recently, genetic variation in the organic cation transporter 1 (Oct1) gene which encodes a protein, OCT1, mediating metformin uptake by the liver, its primary site of action, has been shown alter metformin action. In Oct1-deficient mice the glucose-lowering effects of metformin are completely abolished.
Positive Effects of Metformin:
1) Metformin Treats and Prevents Type 2 Diabetes
2) Metformin Improves Insulin Resistance
3) Metformin Treats Symptoms of PCOS
4) Metformin May Help Prevent and Treat Cancer
5) Metformin Protects the Heart
6) Metformin Lowers Cholesterol
7) Metformin Causes Weight Loss
8) Metformin May Improve Erectile Dysfunction
9) Metformin Slows Aging
10) Metformin May Protect Against Gentamicin (Antibiotic) Damage.


Metabolism of Drugs

Some drugs are chemically altered by the body (metabolized). The substances that result from metabolism (metabolites) may be inactive, or they may be similar to or different from the original drug in therapeutic activity or toxicity. Some drugs, called Prodrugs, are administered in an inactive form, which is metabolized into an active form. The resulting active metabolites produce the desired therapeutic effects. Metabolites may be metabolized further instead of being excreted from the body.
Many substances (such as drugs and foods) affect the cytochrome P-450 enzymes. If these substances decrease the ability of the enzymes to break down a drug, then that drug's effects (including side effects) are increased. If the substances increase the ability of the enzymes to break down a drug, then that drug's effects are decreased.
Factors that affect drug metabolism
1. Physiological factors that can influence drug metabolism include age, individual variation (e.g., pharmacogenetics), enterohepatic circulation, nutrition, intestinal flora, or sex differences.
2. Pathological factors can also influence drug metabolism, including liver, kidney, or heart diseases.


Xenobiotic Toxicity Risk

Xenobiotics have been defined as chemicals to which an organism is exposed that are extrinsic to the normal metabolism of that organism. Without metabolism, many xenobiotics would reach toxic concentrations. Most metabolic activity inside the cell requires energy, cofactors, and enzymes in order to occur.