Gliclazide + Metformin

Gliclazide+ Metformin is an Anti-diabetic Agent belonging to the pharmacological class of second-generation sulfonylurea and biguanides.

Gliclazide+ Metformin has been approved as a treatment for type 2 diabetes mellitus, which is characterized by elevated blood sugar levels. This combination improves insulin sensitivity and release while decreasing the liver's overproduction of glucose.

Gliclazide is absorbed in the gastrointestinal tract, metabolized in the liver, and eliminated primarily through urine. Metformin is absorbed in the small intestine, minimally metabolized, and excreted in urine unchanged. Both drugs are distributed throughout the body, mainly bound to plasma proteins.

The common side effects of Gliclazide+ Metformin are nausea, vomiting, taste change, diarrhoea, abdominal pain, and loss of appetite.

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

Gliclazide+ Metformin is available in India, the United States, Canada, the United Kingdom, Japan, France and Australia.

Gliclazide+ Metformin is an Anti-diabetic Agent belonging to the pharmacological class of second-generation sulfonylurea and biguanides.

Gliclazide: The sulfonylurea drug gliclazide works by attaching itself to the pancreatic beta cells' SUR1 sulfonylurea receptor. Potassium efflux is stopped by this binding, which blocks ATP-sensitive potassium channels. The beta cells, therefore, experience depolarization. The beta cells' voltage-dependent calcium channels open in response to this depolarization. An increase in calcium causes the calcium-binding protein calmodulin to become active, which sets off a series of actions that eventually result in the exocytosis of insulin-containing secretory granules. When insulin is released into the bloodstream, cells are more likely to absorb glucose, lowering blood sugar levels in people with diabetes.

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

Synergistic Benefits: Metformin + Gliclazide work synergistically to manage type 2 diabetes. The sulfonylurea gliclazide effectively decreases blood glucose levels by stimulating the pancreas to release more insulin. The biguanide metformin reduces hepatic glucose synthesis and increases insulin sensitivity. Together, they address hyperglycemia from several perspectives. When metformin is taken with gliclazide, the risk of hypoglycemia is reduced compared to when sulfonylureas are used alone. Additionally, metformin offers benefits such as weight management and cardiovascular protection.

Data Onset of action of Gliclazide+ Metformin typically occurs within 1 to 2 hours after administration.

Data duration of action of Gliclazide+ Metformin effects generally up to 24 hours after administration.

The Data of Tmax (time to peak concentration) of Gliclazide+ Metformin generally reached within 2-6 hours after oral administration.

The Data of Cmax of Gliclazide+ Metformin is achieved within 2-6 hours following administration.

Gliclazide+ Metformin is available in oral tablets.

Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.

As the physician recommends, take the medication orally three times daily before meals or generally with a meal.

Gliclazide+ Metformin can be used in the following health conditions:

Gliclazide: Gliclazide helps increase the amount of insulin your body produces (in the pancreas). It works by boosting the amount of insulin your body generates following a meal and prevents excessive glucose (sugar) release into the blood. In doing so, it decreases your body's blood glucose levels.

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 increasing insulin sensitivity by increasing peripheral glucose uptake and utilization.

For those with type 2 diabetes, the antidiabetic combination of gliclazide + metformin provides several therapeutic advantages. The primary purpose of this combination therapy is to regulate blood sugar levels efficiently. Gliclazide lowers elevated blood glucose levels by stimulating the pancreas to produce insulin. Metformin reduces the synthesis of glucose in the liver and increases insulin sensitivity. By addressing several facets of glucose regulation, this dual method of action improves blood sugar management. This combination also has a lower risk of hypoglycemia than certain other antidiabetic drugs, which makes it a safer choice for a lot of people. Furthermore, metformin may even result in a slight decrease in weight, while gliclazide often does not induce weight gain.

Orally: Gliclazide+ Metformin is available as a tablet that can be taken orally. It is advised to progressively raise the metformin dose at the beginning of treatment to reduce gastrointestinal adverse effects. Take the drug along with food. Avoid breaking, crushing, dissolving, or chewing extended-release pills; instead, swallow them whole. When metformin extended-release pills are partially dissolved in the stool, as has happened with some of them, a healthcare professional should assess glycemic control. The tablet strength determines the precise dosage. Do not double the next dose if missed; instead, take it as soon as possible.

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

Gliclazide+ Metformin has various strengths, such as 40mg+500mg, 60mg+500mg, 80mg+500mg.

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

Starting with oral 2.5 mg–250 mg tablets once daily is recommended for patients with insufficient glycemic control of food and exercise.

The initial dose of 2.5–500 mg can be taken twice daily by diabetic patients whose fasting blood glucose levels are between 280 and 320 mg/dL.

Patients with insufficient glucose control on Glipizide and Metformin are advised to start on an initial dose of 2.5 mg–500 mg or 5 mg–500 mg twice a day by the physician.

Gliclazide+ Metformin should be used in treating type 2 diabetes mellitus, along with appropriate dietary restrictions.

Gliclazide+Metformin is usually taken with meals to reduce the risk of gastrointestinal side effects and to ensure proper absorption.

Excessive alcohol consumption can potentiate the blood sugar-lowering effects of Gliclazide and increase the risk of hypoglycemia (low blood sugar).

Ensure adequate fluid intake, especially if you experience diarrhoea, vomiting, or other conditions that may lead to dehydration, as metformin can affect kidney function.

While taking this combination, it is advised to stay hydrated, consume a rich-balanced diet low in saturated fats and cholesterol—and drink plenty of vegetables, whole grains, fruits, and lean proteins in meals.

The dietary restriction should be individualized as per patient requirements.

Gliclazide+ Metformin may be contraindicated under the following conditions:-

Hypoglycemia may occur if the patient cuts down on their dietary intake if they overdose on purpose or accidentally, or if they have severe physical activity, trauma, or stress. A diabetic meal plan might help lessen the symptoms of hypoglycemia. If hypoglycemia signs and symptoms appear, prompt action should be taken.

During the initial several months, modify the combination's dosage based on blood and urine glucose levels. There aren't many cases, though, of lactic acidosis in liver or kidney disease patients.

The adverse reactions related to Gliclazide+ Metformin can be categorized as:-

The clinically relevant drug interactions of Gliclazide and metformin are briefly summarized here:

When angiotensin enzyme inhibitors (captopril, enalapril), other anti-diabetic medications (insulin, acarbose), beta-blockers, fluconazole, histamine (H) receptor antagonist, monoamine oxidase inhibitors 2 (MAOIs), sulphonamides, and non-steroidal anti-inflammatory agents are administered concurrently, the body becomes more sensitive to insulin and the blood glucose-lowering effect is amplified. As a result, hypoglycemia may occasionally occur. It could be necessary to lower the oral antidiabetic agent's dosage. When starting or stopping treatment, patients using estrogens, oral contraceptives, phenytoin, or quinidine should be continuously watched for a loss of diabetic control.

The most common side effects of Gliclazide+ Metformin include:

Gliclazide+ Metformin should be prudent in the following group of special populations.

Pregnancy Category C: Use with caution if the benefits outweigh the risks.

An increased risk of congenital malformations is linked to elevated blood glucose levels during pregnancy. To keep blood glucose levels as close to normal as possible, most doctors advise using insulin. It is not recommended to use the combination of gliclazide and metformin when pregnant.

Metformin is excreted into milk and reaches levels similar to those in plasma, according to studies done on nursing rats. There are no comparable studies on breastfeeding mothers. The excretion of Gliclazide or its metabolites in breast milk is unknown. Therefore, it is not advised for breastfeeding moms to use Gliclazide and Metformin together. Insulin therapy should be taken into consideration if diet alone is not sufficient to regulate blood glucose levels.

As per FDA, safety and effectiveness in the pediatric population have yet to be established.

Gliclazide with Metformin should only be taken in people with normal renal function since Metformin is known to be eliminated by the kidneys and because patients with impaired renal function are more likely to experience major adverse medication events. Because ageing is linked to a decline in renal function, using gliclazide and metformin together should be done cautiously as one age. Renal function should be regularly evaluated, and care should be exercised when choosing a dosage.

Mild-to-severe: Caution; Dosage modification may be needed.

Severe: Not recommended

Regular assessment of renal function is necessary.

Mild-to-severe: Caution; Dosage modification may be needed.

Severe: Not recommended

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

Overconsumption of Gliclazide+ Metformin could lead to

hypoglycemia (low blood sugar), nausea, vomiting, abdominal discomfort, and lactic acidosis.

There is no specific antidote or treatment for excessive intake of Gliclazide + Metformin. However, immediate medical attention is essential. Gliclazide + Metformin should be terminated immediately when an overdose is suspected or if any unusual symptoms occur after intake.

For hypoglycemia (low blood sugar), consume a source of rapidly absorbed carbohydrates such as glucose tablets, sugar, or honey. Monitor blood glucose levels and repeat treatment if necessary.

If lactic acidosis is suspected, seek immediate medical attention. Treatment may include sodium bicarbonate to correct acidosis, supportive care, and dialysis in severe cases.

Supportive care may involve the use of antiemetic medications to address nausea and vomiting, along with implementing measures to relieve abdominal discomfort.

Gliclazide: Pharmacological characteristics indicate that gliclazide is a hypoglycemic drug of the second generation of sulphonylureas. It induces insulin release from the pancreatic islet of Langerhans beta cells. Peripheral insulin sensitivity is also improved. Insulin dynamics are generally improved, and insulin release is potentiated.

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.

Gliclazide: Although gliclazide is quickly and effectively absorbed, there can be a significant variation across and within individuals. After oral treatment, peak plasma concentrations usually appear 4-6 hours later.

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])

Gliclazide: Gliclazide is extensively distributed throughout the body, primarily affecting red blood cells and plasma. With 94–98% bound to albumin, it has a high affinity for plasma proteins, where it binds most of the proteins.

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)

Gliclazide: Gliclazide undergoes significant hepatic metabolism. The amount of the oral dosage that remains unaltered in the urine is less than 1%. Metabolites comprise conjugates of glucuronic acid as well as oxidized and hydroxylated derivatives.

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

Gliclazide: The kidneys (60–70%) and faeces (10–20%) are the primary systems that eliminate metabolites and conjugates.

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.