Stereochemistry | ACHIRAL |
Molecular Formula | C4H11N5 |
Molecular Weight | 129.1636 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN(C)C(=N)NC(N)=N
InChI
InChIKey=XZWYZXLIPXDOLR-UHFFFAOYSA-N
InChI=1S/C4H11N5/c1-9(2)4(7)8-3(5)6/h1-2H3,(H5,5,6,7,8)
Molecular Formula | C4H11N5 |
Molecular Weight | 129.1636 |
Charge | 0 |
Count |
MOL RATIO
1 MOL RATIO (average) |
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Metformin is the most widely used drug to treat type 2 diabetes, and is one of only two oral antidiabetic drugs on the World Health Organization (WHO) list of essential medicines.
Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. However, we still do not completely understand its mechanisms of action. The main effect of this drug from the biguanide family is to acutely decrease hepatic glucose production, mostly through a mild and transient inhibition of the mitochondrial respiratory chain complex I. In addition, the resulting decrease in hepatic energy status activates AMPK (AMP-activated protein kinase), a cellular metabolic sensor, providing a generally accepted mechanism for the action of metformin on hepatic gluconeogenesis. The use of metformin, the most commonly prescribed drug for type 2 diabetes, was repeatedly associated with the decreased risk of the occurrence of various types of cancers, especially of pancreas and colon and hepatocellular carcinoma.
CNS Activity
Originator
Approval Year
Doses
AEs
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Drug as victim
Sourcing
PubMed
Patents
Sample Use Guides
Recommended Dosing Schedule
Adults
The usual starting dose of GLUCOPHAGE Tablets is 500 mg twice a day or 850 mg once a day,
given with meals. In general, clinically significant responses are not seen at doses below 1500
mg per day. Dosage increases should be made in increments of 500 mg weekly or 850 mg every
2 weeks, up to a total of 2000 mg per day, given in divided doses. The dosage of
GLUCOPHAGE must be individualized on the basis of both effectiveness and tolerability.
Patients can also be titrated from 500 mg twice a day to 850 mg twice a day after 2 weeks. For
those patients requiring additional glycemic control, GLUCOPHAGE may be given to a
maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given
3 times a day with meals.
The usual starting dose of GLUCOPHAGE XR (metformin hydrochloride) Extended-Release
Tablets is 500 mg once daily with the evening meal. In general, clinically significant responses
are not seen at doses below 1500 mg per day. Dosage increases should be made in increments of
500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal. The dosage of
GLUCOPHAGE XR must be individualized on the basis of both effectiveness and tolerability. If
glycemic control is not achieved on GLUCOPHAGE XR 2000 mg once daily, a trial of
GLUCOPHAGE XR 1000 mg twice daily should be considered. If higher doses of metformin
are required, GLUCOPHAGE should be used at total daily doses up to 2550 mg administered in
divided daily doses, as described above. (See CLINICAL PHARMACOLOGY: Clinical
Studies.)
Patients receiving GLUCOPHAGE treatment may be safely switched to GLUCOPHAGE XR
once daily at the same total daily dose, up to 2000 mg once daily. Following a switch from
GLUCOPHAGE to GLUCOPHAGE XR, glycemic control should be closely monitored and
dosage adjustments made accordingly (see CLINICAL PHARMACOLOGY: Clinical
Studies).
Pediatrics
The usual starting dose of GLUCOPHAGE is 500 mg twice a day, given with meals. Dosage
increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day,
given in divided doses. The dosage of GLUCOPHAGE must be individualized on the basis of
both effectiveness and tolerability. Safety and effectiveness of GLUCOPHAGE XR in pediatric
patients have not been established.
Route of Administration:
Oral
Herein, our aim was to examine whether micromolar concentrations of metformin alone could bring about cancer cell death and whether micromolar metformin could increase the cytotoxic effect of commonly used chemotherapies in A2780 and SKOV3 cell lines and primary cultured cancer cells isolated from the peritoneal fluid of patients with advanced ovarian cancer. Our results in cell lines demonstrate that no significant loss of viability or change in cell cycle was observed with micromolar metformin alone; however, we observed cytotoxicity with micromolar metformin in combination with chemotherapy at concentrations where the chemotherapy alone produced no loss in viability.