Gliclazide + Metformin + Voglibose

Gliclazide + Metformin + Voglibose is an anti-diabetic agent belonging to the pharmacological class of second-generation sulfonylureas, biguanides and alpha-Glucosidase inhibitors.

Gliclazide + Metformin + Voglibose is commonly approved for the treatment of type 2 diabetes mellitus in adults, especially when diet and exercise alone are not sufficient to control blood sugar levels.

Gliclazide + Metformin + Voglibose undergo absorption in the gastrointestinal tract. Metformin is distributed widely, primarily eliminated unchanged through the kidneys. Gliclazide is metabolized in the liver and excreted through urine. Voglibose is minimally absorbed, acts locally in the intestine, and is excreted unchanged in faeces.

The common side effect of Gliclazide+ Metformin + Voglibose is low blood glucose levels (hypoglycemia).

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

Gliclazide+ Metformin + Voglibose is available in India, Thailand, Vietnam, Indonesia, Malaysia, the United States, Canada, the United Kingdom, Singapore, the Philippines and Japan.

Gliclazide + Metformin + Voglibose is an anti-diabetic agent belonging to the pharmacological class of second-generation sulfonylureas, biguanides and Alpha-Glucosidase inhibitors.

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).

Voglibose: A synthetic substance called Voglibose, an alpha-glucosidase inhibitor, has strong and long-lasting therapeutic effects against diseases of the sensory, motor, and autonomic nerve systems brought on by diabetes mellitus. Alpha-glucosidase inhibitors are oral anti-diabetic medications used to treat type 2 diabetes mellitus. They function by stopping the breakdown of complex carbohydrates, such as starch. Usually, simple sugars, or monosaccharides, are formed from complex carbohydrates and can be absorbed by the colon. As a result, alpha-glucosidase inhibitors lessen complex carbohydrates' effect on blood glucose.

Synergistic Benefits: Gliclazide + Metformin + Voglibose combination has synergistic effects on type 2 diabetes management by employing diverse mechanisms, enhancing blood sugar control when single or dual therapy falls short. Voglibose, an alpha-glucosidase inhibitor, prevents complex sugar breakdown, inhibiting post-meal blood sugar spikes. Metformin, a biguanide, diminishes liver glucose production, delays intestinal glucose absorption, and heightens insulin sensitivity. Meanwhile, Gliclazide, a sulfonylurea, bolsters pancreas-produced insulin, effectively reducing blood glucose levels, collectively constituting an improved strategy for type 2 diabetes management.

Gliclazide + Metformin + Voglibose 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 twice or thrice daily, preferably before or during meals.

Gliclazide+ Metformin + Voglibose 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.

Voglibose: For those with diabetes mellitus, Voglibose is an alpha-glucosidase inhibitor that lowers blood glucose levels after meals.

Gliclazide + Metformin + Voglibose is used to treat type 2 diabetes. The combination effectively decreases blood glucose levels by reducing the spike in blood glucose after meals by slowing down the breakdown of food in the intestines. It facilitates the removal of extra glucose through urination. The prevention of serious diabetic effects, such as kidney damage, vision problems, nerve problems, and limb loss, is facilitated by this control, which makes blood glucose management essential.

It is indicated for individuals with non-insulin-dependent diabetes (type 2) when blood glucose control cannot be achieved with diet, exercise, and weight loss on their own.

Orally: Gliclazide+ Metformin is available as a tablet that can be taken orally.

It is advised to administer twice or thrice daily, taken with food to avoid an upset stomach at the same time of the day each time for the best results and avoid breaking, crushing, dissolving, or chewing extended-release pills; swallow them whole with a glass of water. If a dose is missed, the individual should take it promptly upon recall. If the missed dose coincides with the upcoming scheduled dose, it is advisable to skip the missed dose and proceed with the regular schedule. Discontinuation of the medication should only occur under medical guidance to prevent fluctuations in blood sugar levels.

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

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

The combination should be given twice or thrice daily with meals and started at a low dose.

Initial amount: This may be initiated once daily and gradually titrated after assessing the therapeutic response.

Based on the initial starting dose of Gliclazide+ Metformin + Voglibose, it may be initiated once daily and

progressively titrated after evaluating the therapeutic response.

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

Take Gliclazide + Metformin + Voglibose with meals to minimize gastrointestinal side effects and ensure proper absorption. Moderate or avoid alcohol consumption due to potential interactions and hypoglycemia risk. Substitute refined carbohydrates with whole grains, increase fibre-rich foods like fruits and veggies, and limit saturated fats in chips, pastries, and biscuits. Use omega-3 fatty acid oils for cooking and choose low-fat dairy products like fat-free milk or low-fat yoghurt.

The dietary restriction should be individualized as per patient requirements.

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

Reduced dietary intake, accidental or intentional overdose, intense exercise, trauma, or stress may induce hypoglycemia. Prescribing a diabetic meal plan can alleviate hypoglycemic symptoms. Immediate intervention is crucial if signs manifest. Lactic acidosis necessitates immediate hospital treatment; discontinuing Metformin and Voglibose is essential, followed by prompt supportive care. For primary diabetes treatment, administer Voglibose if the post-prandial blood sugar is ≥200mg/dl; for patients on oral hypoglycemic drugs or insulin, provide Voglibose when fasting blood sugar exceeds ≈140mg/dl. Maintain regular blood sugar monitoring intervals.

Adjust the combination dosage based on blood and urinary glucose levels during the initial months. Although rare, lactic acidosis has been reported in patients with renal or liver disease. No clinical studies definitively prove the reduction of macrovascular risks with Metformin or other anti-diabetic drugs. Renal function assessment is mandatory before starting and annually during Metformin and Voglibose therapy. Use caution with concurrent medications affecting renal function or Metformin disposition. For planned intravascular contrast studies, temporarily suspend Metformin. Cease administration in cases of cardiovascular collapse, acute heart failure, or conditions linked to hypoxemia. Warn against excessive alcohol intake due to its potentiation of Metformin's effect on lactate metabolism. Avoid Metformin and Voglibose in hepatic disease. Evaluate patients developing abnormality or illness during controlled Metformin usage. Manage hypoglycemia due to insufficient caloric intake or unbalanced exercise by pausing Metformin and Voglibose and initiating temporary insulin. Regularly monitor blood glucose, glycosylated haemoglobin, hematologic parameters, and renal function, especially in patients on other antidiabetic drugs or with digestive disorders, hernia, intestinal issues, or severe hepatic or renal dysfunction.

It is not recommended during pregnancy as it may harm the unborn baby.

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

The clinically relevant drug interactions of Gliclazide + Metformin + Voglibose are briefly summarized here:

The most common side effects of Gliclazide+ Metformin + Voglibose include:

Hypoglycemia, or low blood sugar

Nausea

Changes in taste

Loss of appetite

Diarrhea

Stomach pain

Flatulence

A headache

Rashes on the skin

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

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

For pregnant women with diabetes, insulin is the recommended treatment; gliclazide is not recommended during pregnancy. Whether or not it is gestational, poorly managed diabetes is linked with a higher risk of perinatal mortality and congenital malformations. Reducing the risk of congenital abnormalities can be achieved by maintaining appropriate blood glucose levels close to conception. During pregnancy, stringent normoglycemia must be attained. Since some oral hypoglycemic medications, such as sulfonylureas, may penetrate the placenta and result in hypoglycemia in newborns, insulin should be used in its place. Gliclazide does not appear to have any teratogenic effects in animal tests, but there is insufficient clinical data to determine how it affects pregnant women.

Metformin: Pregnancy Category B; Could be acceptable. Either no danger has been shown by animal research, but human studies have not been conducted, or some risk has been shown by animal studies but not by human studies.

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. If metformin HCl is unnecessary, it is not advisable to use it during pregnancy because research on animal reproduction does not necessarily indicate human response.

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

There are currently no relevant epidemiological data available. Because there are no reported adverse effects of the medication on pregnancy, fetal or embryonic development, parturition, or postnatal development, it should only be administered to pregnant or potentially pregnant women when the potential benefits outweigh the risks.

Gliclazide: Breastfeeding mothers should not use gliclazide. Gliclazide may induce hypoglycemia in nursing infants. Therefore, it's essential to use caution even though it's unclear if it is eliminated in human milk like some sulfonylurea medications are. Breastfeeding is not advised while using gliclazide because of the lack of information regarding this medication's presence in breast milk and the potential risk of newborn hypoglycemia.

Metformin: In nursing rats, metformin excretes into the milk. Since there is no comparable human data, a choice should be made, either stopping metformin or nursing while considering the mother's need for the chemical.

Voglibose: Lactating rats excrete metformin into their milk. Since there is a lack of comparable data for humans, the benefits of continuing the compound in the mother should be considered when deciding whether to stop nursing or stop taking metformin.

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

The safety and effectiveness of Gliclazide+ Metformin + voglibose in elderly individuals should be carefully considered.

Gliclazide+ Metformin + Voglibose should only be taken in patients with normal renal function since Metformin is known to be eliminated via the kidneys and because patients with impaired renal function are more likely to experience major adverse medication events. As age advances, combining Gliclazide, Metformin, and Voglibose should be used cautiously because ageing is associated with decreased renal function. Renal function should be continually monitored, and care should be given when determining a dose.

Kidney impairment (Mild to Severe): Gliclazide + Metformin + Voglibose combination is contraindicated in patients with renal impairment.

Gliclazide + Metformin + Voglibose combination is not recommended in patients with hepatic impairment.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Gliclazide + Metformin + Voglibose.

Overconsumption of Gliclazide+ Metformin + Voglibose could lead to severe hypoglycemia, gastrointestinal disturbances, altered consciousness, seizures, and potentially life-threatening metabolic complications like lactic acidosis.

There is no specific antidote or treatment for excessive Gliclazide + Metformin + Voglibose intake. However, immediate medical attention is essential. Gliclazide + Metformin + Voglibose should be terminated immediately when an overdose is suspected or if any unusual symptoms occur after intake. Activated charcoal can be administered to reduce absorption if the ingestion is recent.

Promptly treat mild hypoglycemic symptoms without loss of consciousness or neurological findings with oral glucose and consider adjusting medication dosage or meal patterns. Continuously monitor patients until their safety is ensured. In severe cases where the individual is unconscious, intravenous dextrose or glucagon may be necessary. If lactic acidosis is suspected due to metformin, provide aggressive treatment, including hemodialysis if needed. Monitor closely for 24 to 48 hours due to potential recurrence. Monitor for lactic acidosis with metformin until patient safety is confirmed. Voglibose delays carbohydrate hydrolysis by competitively inhibiting α-glucosidase enzymes in the small intestine.

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.

Voglibose: Alpha-glucosidase inhibitors are saccharides that function as competitive inhibitors of the alpha-glucosidase enzymes in the small intestine's brush border, which are necessary for digesting carbohydrates. In the small intestine, oligosaccharides, trisaccharides, and disaccharides are hydrolyzed to glucose and other monosaccharides by the membrane-bound intestinal alpha-glucosidases. Acarbose inhibits membrane-bound alpha-glucosidases and also suppresses pancreatic alpha-amylase. In the small intestine lumen, complex starches are hydrolyzed to oligosaccharides by pancreatic alpha-amylase. Compromising these enzyme systems slows down the rate at which complex carbohydrates are metabolized. Because the carbs are not converted into glucose molecules, less glucose is absorbed. The short-term impact of these medication regimens on diabetes patients is a decline in blood glucose levels; the long-term effect is a slight decrease in haemoglobin A1c levels.

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: Incompletely and slowly absorbed from the digestive system. Food reduces and delays absorption slightly. Complete bioavailability: 50%–60%. Time to peak plasma concentration: 2–3 hours (for rapid release); 4–8 hours (for delayed release); 7 hours.

50–60% bioavailability (metformin [fasted])

Voglibose: About 35% of the medicine as a metabolite, and less than 2% of the active ingredient is absorbed from the digestive system.

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)

Voglibose: Time to peak plasma concentration: Approx 1 hour (active drug).

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.

Voglibose: Exclusively metabolized down into at least 13 metabolites in the gastrointestinal tract, with sulfate, methyl, and glucuronide conjugates serving as the main products. Intestinal bacteria and digestive enzymes primarily carry out this process.

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.

Voglibose: Via faeces (about 51% of unabsorbed drug); urine (approximately 34% of inactive metabolites; <2% of unmodified drug and active metabolites). The half-life of elimination: about two hours.