Metformin

Metformin is a biguanide antihyperglycemic drug and first-line medication used to treat type II diabetes. Metformin is categorized as an antihyperglycemic medication. Being effective in lowering blood glucose levels in type II diabetics without causing hypoglycemia makes metformin an antihyperglycemic medication. Because it greatly lowers insulin resistance and plasma fasting insulin levels clinically, it is commonly referred to as an "insulin sensitizer." The medication is also well known for its ability to help individuals with type II diabetes who are obese lose a small amount of weight.

The U.S. Food and Drug Administration (FDA) authorized the antidiabetic drug metformin in 1994 to treat type 2 diabetes. This medicine is commonly used in combination with other antidiabetic medications and comes in both immediate and extended-release forms. Off-label uses of metformin include the treatment and prevention of polycystic ovarian syndrome (PCOS), antipsychotic-induced weight gain, gestational diabetes management, and type 2 diabetes prevention.

BRAND NAMES:

Axpinet: Axpinet is a pill that contains the active ingredient metformin hydrochloride (500 mg). It decreases the amount of glucose absorbed from the diet and generated by the liver. 

Q Met XL: A prescription drug called Q Met XL 500 mg Tablet is given to treat type 2 diabetes. Moreover, Polycystic Ovary Syndrome (PCOS), a menstruation issue in women, is treated with it.

KAZANO: KAZANO tablets include two oral antihyperglycemic medicines used to treat type 2 diabetes: alogliptin (12.5 mg) and metformin HCl (1000 mg).

Glatix-M: Glatix-M Tablet is an anti-diabetic medication that contains Gliclazide 80 mg and Metformin 500 mg. 

Lita M: It is the combination medicine Pioglitazone 15 mg and metformin 500 mg that is used together with exercise and diet to control glucose levels in adults with type 2 diabetes.

 MECHANISM OF ACTION:

Metformin, a biguanide drug, effectively lowers blood glucose levels by blocking glucose production in the liver, limiting gastrointestinal absorption, and boosting insulin sensitivity. As a result, metformin lowers both baseline and postprandial blood glucose levels. Metformin helps in PCOS by lowering insulin levels, which reduces luteinizing hormone and androgen levels. This stability of hormone levels helps to regulate the menstrual cycle in women. Metformin is recommended as a feasible alternative to insulin for gestational diabetes patients. Metformin helps to lower blood glucose levels during pregnancy, which has been associated with congenital abnormalities. According to Facts and Comparisons, metformin was originally classified as a class B pregnancy drug under the old FDA system. Metformin is considered weight-neutral, with the potential to cause mild weight loss. Furthermore, the medicine is unlikely to produce hypoglycemia and may have cardioprotective benefits, increasing its usefulness in diabetes treatment. Metformin normally takes 3 hours to take effect after administration, with a half-life of around 20 hours. Metformin is not extensively metabolized in the liver and has little protein binding. Instead, it is generally removed by the kidneys, largely intact. Therefore, monitoring renal function is critical when using metformin to ensure safe and efficient treatment.

PHARMACODYNAMICS:

Bioavailability: Under fasting conditions, the metformin hydrochloride 500 mg pill has a bioavailability of 50% to 60%.

Food effect: Food intake reduces and slows metformin absorption. Specifically, when metformin is taken with meals, the maximum concentration (Cmax) is 40% lower, the area under the curve (AUC) is 25% lower, and the time to achieve maximum concentration (Tmax) is 35 minutes longer than when taken fasted.

Distribution: The distribution volume for the 850 mg strength of metformin is around 654 ± 358 L. Metformin exhibits minimal plasma protein binding. Stable-state plasma concentration occurs within 24 to 48 hours.
Elimination: Metformin is eliminated unaltered in the urine with no substantial hepatic or biliary excretion. Metformin has an elimination half-life of approximately 6.2 hours.

PHARMACODYNAMICS:

Metformin reduces both basal and PPG. It suppresses excessive hepatic glucose synthesis by reducing gluconeogenesis [30]. Metformin may improve glucose absorption and insulin signaling, decrease fatty acid and triglyceride production, and boost fatty acid β-oxidation. Metformin may improve glucose metabolism in peripheral tissues and reduce meal consumption and intestinal glucose absorption. Metformin does not promote insulin secretion, preventing hypoglycemia and hyperinsulinemia, which are common side effects of other antidiabetic medicines.

DOSAGE AND ADMINISTRATION:

Metformin is an oral medication that is often given in daily doses ranging from 500 to 2550 mg. To reduce the likelihood of gastrointestinal (GI) discomfort, take metformin after a meal. Metformin is available in two formulations: immediate-release, which must be administered twice daily, and extended-release, which must be taken once daily. Daily doses of metformin are typically titrated weekly in 500 or 850 mg increments to lower the risk of side effects in patients taking the medication. Doctors recommend taking metformin at the same time every day. Extended-release metformin tablets are typically taken once a day, preferably with an evening meal and with a full glass of water. Metformin is an effective, safe, and inexpensive medicine that may reduce the risk of cardiovascular disease and death.

CONTRAINDICATIONS:

Metformin is not recommended for people with significant renal impairment (GFR > 30 mL/min/1.73²). This restriction also applies to people who have serum creatinine (SCr) values more than or equal to 1.5 in males and 1.4 in women, or who have abnormal creatinine clearance (CrCl). Furthermore, when using metformin, avoid utilizing drugs that may affect the kidneys. Metformin should be discontinued on the day of surgery. Other metformin contraindications include hypersensitivity and metabolic acidosis. According to the instructions in the medication information, patients with a GFR <60 mL/min/1.73², lactic acidosis risk factors, or undergoing intra-articular contrast should stop taking metformin before getting iodinated contrast agents. If the patient's GFR is back to normal following surgery, metformin can be continued. Nevertheless, the package insert advises stopping metformin if nausea, vomiting, or dehydration occurs due to the possibility of lactic acidosis. Moreover, individuals with unstable heart failure or hepatic impairment should not use metformin.

DRUG INTERACTIONS:

Medication interactions including bupropion, carbonic anhydrase inhibitors, cephalexin, cimetidine, dolutegravir, ethanol, glycopyrrolate, iodinated contrast agents, lamotrigine, ranolazine, and topiramate can increase the risk of lactic acidosis. Additionally, the hypoglycemic impact of metformin may be enhanced by other medication interactions. These medications include quinolones, prothionamide, pegvisomant, salicylates, androgens, alpha-lipoic acid, and selective serotonin reuptake inhibitors. As a result, physicians should keep a close eye on patients who are taking these drugs in addition to metformin.

SIDE EFFECTS:

In general, metformin is regarded as safe and well-tolerated. However, up to 30% of people using metformin experience quite frequent unfavorable GI side effects, like 

• vomiting, 
• nausea, and 
• diarrhea

Less frequently, while taking metformin, some people may have rhinitis, diaphoresis, headaches, hypoglycemia, weakness, and chest discomfort. Extended usage of metformin has been linked to lowered vitamin B12 levels; hence, medical practitioners should closely monitor their patients, particularly those who suffer from peripheral neuropathy or anemia. Vitamin B12 supplements could be required in certain circumstances.

TOXICITY:

Metformin overdose can lead to hypoglycemia and lactic acidosis. If clinicians suspect lactic acidosis due to toxic metformin levels, they immediately discontinue the medication and begin hemodialysis. Metformin is easily dialyzable due to its low molecular weight and limited protein binding. Because no specific antidote is currently available, metformin toxicity treatment consists mostly of supportive measures.

STORAGE CONDITIONS:

Protect from sunlight. Maintain at 15 to 30 ̊ C.