Glipizide + Metformin

Glipizide + Metformin is an Anti-diabetic Agent belonging to the pharmacological class of second-generation sulfonylureas and biguanide.

Glipizide and metformin are approved for managing adult-onset type 2 diabetes. Treating insulin resistance and inadequate insulin secretion is recommended to enhance glycemic control and lower blood sugar levels in people with this metabolic disease.

The side effects of Glipizide + Metformin include low blood glucose levels (hypoglycemia), such as sweating, dizziness, headache, and shaking.

Glipizide + Metformin is available as a tablet for convenient administration.

Glipizide + Metformin is available in various countries worldwide, including the United States, Canada, the United Kingdom, Germany, Australia, and many others.

Glipizide + Metformin is an Anti-diabetic Agent belonging to the pharmacological class of second-generation sulfonylureas and biguanide.

Glipizide: High blood glucose levels are a common metabolic disease known as type 2 diabetes mellitus (T2DM), impacted by lifestyle, environmental, and genetic factors. Because it encourages the entry of glucose into cells for storage, the hormone insulin is essential in controlling blood sugar levels. Insulin resistance decreased insulin production, and malfunctioning beta cells in the pancreas are the causes of type 2 diabetes. Early management of long-term problems, such as cardiovascular risks, through dietary and activity modifications is imperative. Glipizide is a sulfonylurea that acts mainly on ATP-sensitive potassium channels to increase calcium influx and induce insulin release, improving insulin output from functioning pancreatic beta cells. It also helps regulate blood sugar by enhancing insulin receptor activation and preventing the overproduction of glucose by the liver.

Metformin: Metformin decreases hepatic glucose production, reduces absorption of glucose in the intestine and improves the insulin sensitivity (increases peripheral glucose uptake and utilization).

The onset of action of metformin was up to 2 weeks.

Synergistic Benefits: Glipizide + metformin is a sulfonylurea + biguanide drug combination that helps persons with type 2 diabetes control their blood sugar levels. While metformin lowers glucose synthesis by the liver and increases insulin sensitivity in bodily tissues, glipizide stimulates the pancreas to produce more insulin. When taken as a whole, they target several facets of glucose regulation, improving blood sugar control. This combination may reduce the risk of low blood sugar associated with Glipizide monotherapy and may be more effective than using either medication alone.

Data duration of action of Glipizide + Metformin effects typically lasts several hours. Glipizide's effects may last up to 24 hours, while metformin's can last up to 12 hours.

The Cmax (peak plasma concentration) of Glipizide + Metformin typically ranges from 2 to 4 hours after oral administration.

Glipizide + Metformin is available in tablets.

Tablets: To be swallowed whole with water/liquid.

As the physician recommends, take the medication orally once daily, generally with or without a meal.

Glipizide + Metformin is an Anti-diabetic Agent belonging to the pharmacological class of second-generation sulfonylureas and biguanide.

Glipizide: To efficiently lower blood glucose levels, glipizide works by blocking the excessive release of sugar into the bloodstream and boosting insulin synthesis. It provides a convenient once-daily dosage schedule with only minor side effects. Diabetes consequences such as kidney damage, eye problems, neuropathy, and cardiovascular disorders can be avoided by maintaining blood sugar control. When combined with a healthy lifestyle, consistent medication use can help people with diabetes live longer and have better quality of life.

Metformin: Metformin improves glucose tolerance by lowering basal and postprandial plasma glucose. It exerts its effect by decreasing hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis, delaying intestinal glucose absorption, and improving the insulin sensitivity by increasing peripheral glucose uptake and utilization.

For people with type 2 diabetes, glipizide + metformin efficiently manages blood glucose levels by combining two distinct drug classes. Glipizide increases the body's insulin production, but metformin lessens the liver's overproduction of glucose. By reducing the chance of complications and enhancing overall diabetes care, this dual mechanism helps lower blood sugar levels.

Indicated as an additive to diet and exercise in patients with type 2 diabetes mellitus to enhance glycemic control.

This combination therapy, when indicated, can help individuals with type 2 diabetes manage their weight effectively.

Orally: Glipizide + metformin is available as a tablet that can be taken orally. Glipizide + metformin tablets should be taken twice daily with food to decrease the risk of gastrointestinal side effects related to metformin; splitting the pills should be avoided.

It is typically taken by mouth with a full glass of water. A healthcare provider should determine the dosage and frequency of administration based on an individual's specific medical condition and needs. Still, consistent timing and adherence to the prescribed regimen are crucial for effective diabetes management.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Glipizide + Metformin is available in the form of Oral tablets.

First-line therapy: begin with 2.5 mg/250 mg (glipizide/metformin) PO once daily with meals.

If the plasma glucose level when fasting is between 280 and 320 mg/dL, take 2.5 or 500 mg PO every 12 hours.

Titrate every two weeks to 10/2000 mg of daily split dosages.

DM Type 2 Not Enough Controlled on Metformin and/or Sulfonylurea

Second-line therapy: begin with 2.5/500 mg or 5/500 mg PO every 12 hours while eating.

Titrate in divided doses to a maximum of 20/2000 mg daily.

Glipizide + Metformin should be used in treating Type 2 Diabetes Mellitus, along with appropriate nutritional limits.

Taking Alogliptin + metformin with food is advised for safe and effective use to lower the risk of gastrointestinal side effects. Because alcohol can interfere with blood sugar regulation, limiting consumption and talking to a healthcare professional about it is best. Long-term Metformin use may result in a vitamin B12 deficit, which should be considered. B12 supplements may be necessary. Watch out for symptoms of hypoglycemia and lactic acidosis, a rare but dangerous side effect. If surgery is scheduled, inform the surgical team about any medications you take and talk to the physician about potential drug interactions. Effective diabetes management requires following doctor's instructions about medication use, dosage adjustments, dietary advice, and routine check-ups. Advice may differ depending on individual health conditions.

It is also advised to stay hydrated, maintain a rich, balanced diet low in saturated fats and cholesterol, and consume plenty of vegetables, whole grains, fruits, and lean proteins to help manage your overall health and blood sugar levels effectively.

The dietary restriction should be individualized as per patient requirements.

Glipizide + metformin may be contraindicated in patients with the following conditions:-

Individuals deficient in glucose-6-phosphate dehydrogenase may be susceptible to hemolytic anaemia caused by sulfonylureas.

When compared to diet alone or diet plus insulin, the administration of oral hypoglycemic medications has been associated to a higher risk of cardiovascular death; however, there is a lack of evidence to support this link, and multiple studies—including a sizable prospective trial—have found no evidence of this association; This risk does not seem to be shared by metformin; Other medicines are preferred in patients with established atherosclerotic cardiovascular disease.

The use of metformin for an extended period of time is linked to a deficiency in vitamin B12. Patients taking metformin should have their hematologic parameters measured annually, and any abnormalities should be appropriately investigated and managed. Some people may be more likely to develop subnormal vitamin B12 levels due to inadequate calcium absorption or intake of B12. These patients may benefit from routine serum vitamin B12 measurements every two to three years.

As ageing is associated with reduced renal function, the drug should be carefully titrated in older patients to determine the minimum dose necessary for an adequate glycemic effect. Renal function should also be regularly monitored in older patients, especially those older than 80, and the drug should generally not be titrated to the maximum dose in these patients.

Acute congestive heart failure(CHF), acute myocardial infarction, and other hypoxemia-related conditions have been linked to lactic acidosis and can potentially cause prerenal azotemia. If these events transpire in patients receiving this therapy, the medication should be stopped immediately.

It is well known that alcohol increases the way that metformin affects lactate metabolism. Hence, patients should be cautioned against consuming large amounts of alcohol, either acutely or chronically, while receiving; alcohol may also raise the risk of hypoglycemia because of its impact on the liver's ability to produce glucose.

Evaluation for signs of ketoacidosis or lactic acidosis should be conducted as soon as possible in a patient with type 2 diabetes who previously received metformin and had average blood glucose and blood lactate, pyruvate, and pH levels. If either type of acidosis develops, the medication must be stopped immediately, and other necessary corrective actions must be started.

Patients with clinical or test signs of hepatic dysfunction should typically avoid this medication since decreased hepatic function has been linked to some occurrences of lactic acidosis.

When a surgical procedure is performed, therapy should be temporarily stopped (except for simple operations that do not involve restricted food or fluid intake), and it should not be resumed until the patient has resumed oral intake. Renal function has been assessed as usual.

Renal function should be evaluated and confirmed as usual before starting therapy and at least once a year afterwards. In patients where the development of renal dysfunction is predicted, renal function should be evaluated more frequently, and treatment should be stopped if there is evidence of renal impairment.

Hypoglycemia: When using this medicine combination, it is essential to select the right patient and follow the proper dosage and instructions to avoid hypoglycemia. Alcohol consumption, imbalanced activity, and the concurrent use of other medications that lower blood sugar all increase the risk of low blood sugar. Drug levels and the risk of hypoglycemia can also be raised by renal and hepatic impairment. Elderly people, undernourished people, and people with specific medical disorders are more vulnerable, and it can be challenging to diagnose hypoglycemia when using beta-blockers.

Iodinated contrast imaging procedures: When undergoing an iodinated contrast imaging technique, stop taking metformin if you have an eGFR of 30 to 60 mL/minute/1.73 m², if you have a history of liver disease, alcoholism, or heart failure, or if you will be receiving intra-arterial iodinated contrast.

Reassess eGFR 48 hours following the imaging procedure, and if renal function is stable, continue metformin.

The adverse reactions related to Glipizide + metformin can be categorized as

The clinically relevant drug interactions of glipizide and metformin are briefly summarized here.

Notable interactions include an elevated risk of hypoglycemia when used with alcohol or other glucose-lowering medications, especially in patients who are malnourished. Renal insufficiency may cause medication levels to rise, whereas hepatic insufficiency may cause Glipizide levels to rise and gluconeogenic ability to decrease, raising the risk of hypoglycemia. Furthermore, Glipizide + Metformin may impact the absorption of vitamin B12 and interact with medications that block beta-adrenergic transmission, thereby concealing hypoglycemia. These interactions call for careful monitoring and dosage modifications when taking this drug.

The most common side effects of Glipizide + Metformin include-

Teratogenic Effects: Pregnancy Category C (FDA): Use caution if the benefits outweigh the risks.

According to recent data, there may be a link between elevated blood glucose levels during pregnancy and a higher risk of congenital disabilities. Most medical professionals advise using insulin to keep blood glucose levels as near to normal as feasible when pregnant. Glipizide and metformin hydrochloride tablets should be avoided during pregnancy unless necessary, as research on animal reproduction does not necessarily indicate human response.

Pregnant women taking glipizide and metformin hydrochloride tablets, or any combination of the two, have not been the subject of sufficient, carefully conducted research. Glipizide and metformin hydrochloride tablets have not been the subject of animal experiments. The data below are derived from research done using each product separately.

Certain sulfonylurea medications are known to be excreted in human milk. However, it is still being determined if glipizide is as well. Metformin is usually excreted into milk and reaches levels similar to those in plasma, according to studies done on nursing rats. No research identical to this has been done on breastfeeding mothers. Given the possibility of hypoglycemia in nursing infants, the mother's need for the medication should be considered while deciding whether to stop breastfeeding or to stop taking glipizide and metformin hydrochloride tablets. Insulin therapy should be regarded as if glipizide and metformin hydrochloride pills are eliminated, and diet alone is insufficient to regulate blood glucose.

As per FDA, safety and effectiveness in the pediatric population have not been established.

Since reduced hepatic, renal, or cardiac function is more common in older patients, concurrent conditions or other pharmacological therapies, and lactic acidosis is a higher threat, dose selection for these patients should generally be cautious, usually beginning at the low end of the dosing range. In older individuals, evaluate renal function more often.

Before starting to use metformin hydrochloride and glipizide tablets, as well as regularly afterwards, evaluate renal function.

Metformin hydrochloride tablets and glipizide are contraindicated for patients whose estimated glomerular filtration rate (eGFR) is less than 30 mL/minute/1.73 m2.

When a patient's eGFR is between 30 and 45 mL/minute/1.73 m2, it is not advised to start giving them metformin hydrochloride and glipizide tablets.

Determine if continuing medication is beneficial or risky for individuals taking glipizide and metformin hydrochloride tablets whose eGFR drops below 45 mL/min/1.73 m2.

If the patient's eGFR drops below 30 mL/minute/1.73 m2, discontinue glipizide and metformin hydrochloride tablets.

Hepatic impairment: Avoid use

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of glipizide + metformin.

Overconsumption of Glipizide + metformin could lead to can lead to severe hypoglycemia. Signs and symptoms include confusion, shakiness, sweating, rapid heartbeat, and loss of consciousness. Seizures may also occur.

There is no specific antidote or treatment for excessive intake of Glipizide + Metformin. However, immediate medical attention is essential. Glipizide + Metformin should be terminated immediately when an overdose is suspected or if any unusual symptoms occur after intake. Activated charcoal or gastric lavage may also be considered if the overdose is detected shortly after ingestion to reduce absorption.

Assuring a patent airway, maintaining the patient's vital signs, and administering enough oxygen are the initial steps for managing Glipizide + Metformin overdosage. Intravenous (IV) dextrose, or glucose, is given as treatment for hypoglycemia. Intravenous or intramuscular glucagon injection may be considered if the patient is not improving after receiving dextrose via IV. Diazoxide, which decreases insulin release, may also be administered in severe cases. Hospitalization is frequently required for observation and additional therapy; continuous monitoring—including blood glucose levels—is crucial.

Glipizide: Glipizide tends to reduce blood sugar levels quickly by inducing the pancreas to release more insulin; however, this action relies on the pancreatic islets' beta cells being functional. Oral sulfonylurea hypoglycemic medications may have extrapancreatic effects as part of their mechanism of action. It is still being determined precisely how glipizide decreases blood sugar levels when used over an extended period of time. Glipizide's induction of insulin secretion in response to a meal is crucial for human health. After at least six months of treatment, the postprandial insulin response is still improved, but fasting insulin levels do not rise even with long-term glipizide administration.

Metformin: Metformin is an antihyperglycemic medication that lowers basal and postprandial plasma glucose levels in people with type 2 diabetes, improving their glucose tolerance. Its pharmacologic modes of action are distinct from those of other oral antihyperglycemic medication groups. Metformin increases peripheral glucose uptake and utilization, which lowers intestinal glucose absorption, reduces hepatic glucose synthesis, and enhances insulin sensitivity. Metformin, unlike sulfonylureas, does not result in hyperinsulinemia or hypoglycemia in either type 2 diabetes patients or healthy persons. Metformin medication does not alter insulin secretion, although it may reduce the plasma insulin response throughout the day and insulin levels while fasting.

Glipizide: Glipizide is consistently, rapidly, and completely absorbed in the gastrointestinal tract. When given orally to patients with type 2 diabetes, glipizide had a 100% absolute bioavailability. Within 6 to 12 hours after the first dose, the maximum plasma concentrations are anticipated to be attained. The steady-state plasma concentrations of glipizide from an extended-release oral formulations remain constant throughout the 24-hour dosing period. The presence of meals in healthy participants slowed the absorption of glipizide, although the overall absorption was unaffected.

Metformin: Slowly and incompletely absorbed from the gastrointestinal tract. Food slightly delays and decreases the extent of absorption. Absolute bioavailability: 50-60%. Time to peak plasma concentration: 2-3 hours (immediate-release); 7 hours, range: 4-8 hours (extended-release).

Bioavailability: 50-60% (metformin [fasted])

Glipizide: After giving single doses to individuals with type 2 diabetes mellitus, the mean volume of distribution was around 10 L. The amount of the drug and its metabolites found in the foetuses of pregnant female mice and rats was negligible to nonexistent in these trials. The risk of glipizide in foetuses or babies cannot be completely ruled out because other sulfonylurea medications have been proven to pass through the placenta and into breast milk.

Protein-bound: 99%

Vd: 10-11 L

Metformin: Concentrates in the liver, kidney and gastrointestinal tract. It crosses the placenta and then enters breast milk (small amounts). Volume of distribution: 654 ± 358 L.

Protein-bound: Negligible (metformin)

Glipizide: The primary metabolites of glipizide are produced through aromatic hydroxylation in the liver, where glipizide is vulnerable to metabolism. It has been found that these principal glipizide metabolites are pharmacologically inactive. In contrast, a minor metabolite called acetylaminoethyl benzine, which makes up less than 2% of the original dosage and has one-tenth to one-third as much hypoglycemic effect as the parent chemical, is generated. Albumin is the primary plasma protein to which glipizide is 98–99% bound in blood proteins.

Metformin: Excreted unchanged in the urine and did not undergo any specific hepatic metabolism (no metabolites have been found in humans) or biliary excretion.

Glipizide: Less than 10% of the original dose of the medication can be found in the urine and faeces as unchanged glipizide, which is mainly removed through hepatic biotransformation. Glipizide's metabolites are eliminated in the urine in around 80% of cases and the faeces in 10%.

Half-life: 2-5 hr

Excretion: Urine (63-90%); feces: (10%)

Metformin: With a plasma elimination half-life of roughly 6.2 hours, 90% of the absorbed medication is excreted via the renal pathway during the first 24 hours following oral administration. The elimination half-life of blood is roughly 17.6 hours, indicating that the erythrocyte bulk could constitute a distribution compartment.