Remogliflozin Etabonate + Metformin
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Sodium-glucose cotransporter-2 (SGLT2) inhibitors, Biguanide, Therapy Class:
Antidiabetic Agent, Approved Countries
India, the United States, Canada, the United Kingdom, Germany, France and Australia.
Remogliflozin Etabonate + Metformin is an anti-diabetic agent belonging to the pharmacological class of Sodium-glucose transport protein 2 (SGLT2) Inhibitors and biguanides.
Remogliflozin Etabonate + Metformin has been approved for the treatment of type 2 diabetes mellitus along with diet & exercise to help improve glycemic control to lower blood sugar levels effectively.
Remogliflozin etabonate is well-absorbed orally, undergoes minimal metabolism, and is eliminated primarily unchanged through urine. Metformin is also well-absorbed orally, has negligible metabolism, and is primarily eliminated unchanged through the kidneys, with minimal distribution into tissues.
Remogliflozin Etabonate + Metformin side effects that commonly occur include taste change, urinary tract infections, nausea, and loss of appetite.
Remogliflozin Etabonate + Metformin is available as a tablet for convenient administration.
Remogliflozin Etabonate + Metformin is available in India, the United States, Canada, the United Kingdom, Germany, France and Australia.
Remogliflozin Etabonate + Metformin is an anti-diabetic agent belonging to the pharmacological class of Sodium-glucose transport protein 2 (SGLT2) Inhibitors and biguanides.
Remogliflozin Etabonate: Remogliflozin etabonate inhibits glucose reabsorption in the kidneys by inhibiting SGLT2. As a result, blood glucose levels are lowered due to increased glucose excretion in urine. It lowers blood sugar levels independently of insulin action by blocking the body from reabsorbing glucose and encouraging the excretion of excess glucose. Using the kidneys to eliminate excess glucose helps control hyperglycemia and provides a different approach from other antidiabetic drugs, concentrating on insulin synthesis or sensitivity. In people with type 2 diabetes, the inhibition of SGLT2 helps with urine excretion of glucose, which improves glycemic control.
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 + remogliflozin etabonate works synergistically to manage type 2 diabetes. Metformin reduces liver glucose synthesis and improves tissue insulin sensitivity, while remogliflozin etabonate encourages glucose excretion through urine, lowering blood sugar levels. When taken as a pair, they reduce blood glucose levels more successfully than alone. Combination therapy is an effective option for managing type 2 diabetes because it improves glucose control and may also have other benefits like weight loss, a decreased risk of hypoglycemia, and improved cardiovascular outcomes.
Remogliflozin Etabonate + 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 twice daily before meals or generally with a meal.
Remogliflozin Etabonate + Metformin can be used in the following health conditions:
- Management of Type 2 Diabetes to improve glycemic control in adults.
- Cardiovascular protective effects in individuals with type 2 diabetes.
- Helps in weight management in individuals with type 2 diabetes.
Remogliflozin Etabonate: Controlling elevated blood sugar levels is the main objective of type 2 diabetes mellitus therapy. Urine is used to get rid of extra glucose in this way. It is necessary to lower blood glucose, and controlling and lowering high blood sugar levels is essential to diabetes treatment.
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.
Remogliflozin Etabonate + Metformin potentially reduces the risk of hypoglycemia, aiding weight management and improving overall glycemic control in affected individuals. To effectively manage diabetes, the blood glucose levels must be reduced. Controlling blood sugar levels will lower the likelihood of any of the severe complications of diabetes, including kidney damage, eye damage, nerve problems, and amputation of limbs. The risk of cardiac disease and stroke can be decreased with proper diabetes management. Individuals can live longer if they take this medication consistently and follow a healthy diet and exercise routine.
For individuals with type 2 diabetes mellitus who are 18 years of age or older, remogliflozin etabonate plus metformin is indicated.
- As an adjunct to food and exercise to enhance glycemic control:
- Remogliflozin and metformin tablets alone are already being used in individuals who are not adequately managed on the maximum tolerated dose of the medication.
Orally: Remogliflozin Etabonate + Metformin is available as a tablet that can be taken orally.
It is advised to administer two times daily before meals and avoid breaking, crushing, dissolving, or chewing pills; swallow them whole with a glass of water. It is best to take it regularly at a fixed time each day following the physician's prescribed schedule for regular and evenly spaced intervals because the dose and duration of therapy are individualized per specific conditions to achieve the most effective and successful treatment outcome.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Remogliflozin Etabonate + Metformin has various strengths, such as 100 mg + 500 mg and 100 mg+ 1000 mg.
Remogliflozin Etabonate + Metformin is available in the form of Oral tablets.
Dosage Adjustment for Adult Patients
Dose: The daily recommended dose of Remogliflozin Etabonate + Metformin for adults is one tablet PO every 12 hours, i.e. BD, considering a maximum dose of 200 mg.
Remogliflozin Etabonate + Metformin should be used in treating type 2 diabetes mellitus, along with appropriate dietary restrictions.
Remogliflozin Etabonate Metformin is usually taken with meals to lower the risk of gastrointestinal (GI) side effects and to ensure proper absorption.
Correct dehydration and electrolyte imbalances. Monitor kidney function and manage acid-base imbalances, especially in suspected cases of lactic acidosis due to metformin.
Patients should limit high-carbohydrate, high-sugar foods to maintain stable glucose levels.
This involves substituting carbohydrates with whole grains, fruits, vegetables, and lean proteins, as carbohydrates can be converted into sugars, resulting in elevated blood sugar levels.
The dietary restriction should be individualized as per patient requirements.
Remogliflozin Etabonate + Metformin may be contraindicated under the following conditions:-
- Hypersensitivity to any of the medication's ingredients
- Any kind of acute metabolic acidosis, including diabetic ketoacidosis and lactic acidosis pre-coma from diabetes.
- GFR < 30 ml/min indicates severe renal failure.
- Acute diseases such as shock, severe infection, and dehydration might affect renal function.
- Conditions that can lead to tissue hypoxia, including shock, decompensated heart failure, respiratory failure, recent myocardial infarction, acute disease, or the progression of chronic disease.
- Alcoholism, acute alcohol intoxication, and liver impairment.
- Remogliflozin etabonate and metformin may lead to renal impairment or acute kidney injury. Monitor renal function routinely before and during therapy, adjusting dosage as needed in patients with renal complications.
- Monitoring is essential for hypoglycemia risk, particularly in combination with insulin or secretagogues. Adjusting doses is crucial to mitigate the potential for low blood sugar levels.
- Patients should exercise caution with medications impacting kidney function or electrolytes. If using potassium-sparing diuretics or supplements, monitor potassium levels. Promptly report signs of dehydration, excessive thirst, or irregular heartbeats for assessment.
- Be vigilant for signs of metabolic acidosis, especially in individuals with impaired renal function. If suspicion develops, stop therapy immediately and provide appropriate care.
- For the risk of hypoglycemia, monitoring is crucial, especially when combined with insulin or secretagogues. Modifying dosages is essential to reduce the risk of hypoglycemia.
- Patients should be informed about heightened susceptibility to genital mycotic infections. Encourage seeking medical guidance if experiencing itching or discharge while on Remogliflozin etabonate and metformin therapy.
Alcohol Warning
It is unsafe to consume Remogliflozin etabonate + Metformin with alcohol.
Breast Feeding Warning
There is insufficient scientific evidence regarding the use and safety of Remogliflozin etabonate + Metformin for breastfeeding populations.
Pregnancy Warning
There is insufficient scientific evidence regarding the use and safety of Remogliflozin etabonate + Metformin in pregnant populations.
Food Warning
Avoid excessive intake of high-sugar or high-fat foods. Take low fat and a low sugar diet.
The adverse reactions related to Remogliflozin Etabonate + Metformin can be categorized as: -
- Common Adverse Effects: Gastrointestinal issues like nausea, diarrhea, or abdominal discomfort.
- Less Common Adverse Effects: Urinary tract infections or headaches
- Rare Adverse Effects: Severe hypoglycemia or allergic reactions.
The clinically relevant drug interactions of Remogliflozin Etabonate + metformin are briefly summarized here:
- Insulin and Insulin Secretagogues: Concomitant use of Remogliflozin etabonate and metformin with insulin or insulin secretagogues (e.g., sulfonylureas) may potentiate hypoglycemia. Close monitoring and dosage adjustments are essential to prevent low blood sugar.
- Diuretics: Diuretics, particularly loop diuretics, may increase the risk of dehydration when used alongside Remogliflozin etabonate and metformin. Monitor fluid status regularly to prevent dehydration-related complications.
- Cationic Drugs: Metformin is known to interact with cationic drugs, such as cimetidine, causing alterations in metformin elimination and potentially increasing blood levels. Avoid coadministration or monitor closely for adverse effects.
- Medications Affecting Renal Function: Drugs impacting kidney function, like NSAIDs (non-steroidal anti-inflammatory drugs) or ACE inhibitors, when combined with Remogliflozin etabonate and metformin, may heighten the risk of kidney impairment or increase serum creatinine levels. Monitoring renal function is crucial.
- Alcohol: Excessive alcohol intake may potentiate the risk of lactic acidosis associated with metformin. It is advisable to limit alcohol consumption or avoid it altogether while on this medication combination.
The most common side effects of Remogliflozin Etabonate + Metformin include:
Infection of the urinary system
Nausea
Diarrhea
Pain in the stomach
Vomiting
Loss of appetite
Reduced blood glucose level, or hypoglycemia
Remogliflozin Etabonate + Metformin should be prudent in the following population group.
- Pregnancy and lactating Mothers
Pregnancy Category (FDA): Not specified as limited available data is available on its use during pregnancy.
Remogliflozin etabonate's effects in pregnant/lactating women are unknown, including its presence in breast milk. Avoid during pregnancy/breastfeeding; use contraception. Insulin is preferred for diabetes during pregnancy. Limited data exist for Remogliflozin and Metformin in lactation; caution is advised due to uncertain infant risks.
- Pediatric Use
As per FDA, safety and effectiveness in the pediatric population have yet to be established.
- Geriatric Use
Usually, age-based dose adjustments are not advised. It is essential to consider renal function and the possibility of fluid depletion. Because elderly persons are more susceptible to reduced renal function and because the kidney excretes metformin,
In these patients, cautious usage of metformin and remogliflozin is advised. Renal function monitoring is essential, especially in older patients, to help prevent lactic acidosis associated with metformin. A higher risk of volume depletion should be considered in patients 75 years of age and above. Therapy beginning in patients 75 years of age and older is not advised due to the limited therapeutic experience with remogliflozin in this population.
Dose Adjustment in Kidney Impairment Patients:
eGFR 60-89 ml/min: Metformin: Maximum daily dose is 3000mg. Remogliflozin: Maximum daily dose is 200mg. Consider dose reduction with declining renal function.
eGFR 45-59 ml/min: Metformin: Maximum daily dose is 2000mg. Remogliflozin should not be initiated.
eGFR 30-44 ml/min: Maximum daily dose is 1000mg. Remogliflozin is not recommended.
eGFR <30 ml/min: Metformin is contraindicated. Remogliflozin is not recommended.
Dose Adjustment in Hepatic Impairment Patients:
There is insufficient scientific evidence regarding the use and safety of Remogliflozin Etabonate + Metformifor use in this population.
Signs and Symptoms
The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Remogliflozin Etabonate + Metformin. Overconsumption of Remogliflozin Etabonate + Metformin could lead to severe hypoglycemia, dehydration, electrolyte imbalances, gastrointestinal disturbances, and, potentially, lactic acidosis.
Management
There is no specific antidote or treatment for excessive Remogliflozin Etabonate + Metformin intake. However, immediate medical attention is essential. Remogliflozine etabonate + Metformin should be terminated immediately when an overdose is suspected or if any unusual symptoms occur after intake. Treatment might involve symptomatic and supportive measures.
When managing severe hypoglycemia, administer glucose intravenously or orally. If the patient fails to respond, consider glucagon. Redress electrolyte imbalances and dehydration. Monitor the renal function and manage acid-base abnormalities, particularly if metformin-related lactic acidosis is suspected.
Hemodialysis may be considered in severe cases to remove the drugs from the bloodstream. Patients should be closely observed for any signs of lactic acidosis, a rare but potentially life-threatening complication, and treated accordingly.
Pharmacodynamics
Remogliflozin Etabonate: Remogliflozin etabonate is quickly absorbed and transforms into remogliflozin in its active state. Food consumption slightly postpones the peak concentration without changing the overall exposure, giving administrators more choices. Mean Cmax and AUC0-tau values are observed at steady state levels at 100 mg and 250 mg dosages in Indian individuals with type 2 diabetes. In one investigation, absorption of over 93% was noted. Given their nearly complete absorption, remogliflozin etabonate and remogliflozin function as P-gp substrates rather than inhibitors, suggesting that P-gp inhibitors have no apparent effect on their pharmacokinetics.
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.
Pharmacokinetics
Absorption
Remogliflozin Etabonate: Remogliflozin etabonate is swiftly absorbed and converted to active forms like remogliflozin. Remogliflozin etabonate is absorbed quickly and converted to active forms like remogliflozin. Absorption exceeds 93%, acting as a P-gp substrate, not an inhibitor. Therefore, P-gp inhibitors aren't expected to affect its pharmacokinetics.
Metformin: Slow, incomplete gastrointestinal absorption. Food slightly delays and reduces absorption. Bioavailability: 50-60%. Peak plasma concentration: 2-3 hours (immediate-release); 7 hours (extended-release).
Bioavailability: 50-60% (Metformin [fasted])
Distribution
Remogliflozin Etabonate: Approximately 65% of remogliflozin is bound to plasma proteins. The distribution of remogliflozin etabonate or remogliflozin was not preferential to blood cells, nor did remogliflozin or its metabolites selectively associate with tissues that contained melanin.
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)
Metabolism
Remogliflozin Etabonate: Numerous metabolic processes occur throughout the extended metabolism of remogliflozin etabonate, including oxidation, glucose loss, glucuronidation, N-dealkylation, O-dealkylation, and loss of ethyl hydrogen carbonate.
Metformin: Excreted unchanged in the urine and did not undergo specific hepatic metabolism (no metabolites have been found in humans) or biliary excretion.
Elimination
Remogliflozin Etabonate: The prodrug's average plasma half-life within the identical investigation ranged from 0.4 to 0.7 hours. A little over 11% of the dose was recovered as remogliflozin in the urine of the radiolabeled AME trial, which expelled about 93% of the drug; most drug-related material is removed in the urine as inactive glucuronide metabolites.
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.
Therapeutic benefits of a combination of Remogliflozin Etabonate and metformin
- Improved Glycemic Control: To lower blood sugar levels effectively, enhancing glucose control in individuals with type 2 diabetes.
- Reduced Risk of Hypoglycemia: May decrease the risk of hypoglycemia compared to using certain anti-diabetic medications alone, promoting safer glycemic management in affected individuals.
- Weight Management: Might help in weight management for individuals with type 2 diabetes, potentially resulting in moderate weight loss due to the glucose-lowering and metabolic effects.
- Hussey, E.K., Kapur, A., O’Connor-Semmes, R. et al. Safety, pharmacokinetics and pharmacodynamics of remogliflozin etabonate, a novel SGLT2 inhibitor, and metformin when co-administered in subjects with type 2 diabetes mellitus. BMC Pharmacol Toxicol 14, 25 (2013). https://doi.org/10.1186/2050-6511-14-25
- Dobbins, R., Hussey, E.K., O’Connor-Semmes, R. et al. Assessment of safety and tolerability of the remogliflozin etabonate (GSK189075) when administered with a total daily dose of 2000 mg of metformin. BMC Pharmacol Toxicol 22, 34 (2021). https://doi.org/10.1186/s40360-021-00502-0
- Viswanathan Mohan, Ambrish Mithal, Shashank R Joshi, S R Aravind & Subhankar Chowdhury (2020) Remogliflozin Etabonate in the Treatment of Type 2 Diabetes: Design, Development, and Place in Therapy, Drug Design, Development and Therapy, 14: 2487-2501, DOI: 10.2147/DDDT.S221093
- Sengupta, S., Sengupta, S., & Katare, S. (2021). A real-world clinical experience on remogliflozin etabonate's effectiveness in managing Indian patients with type II diabetes mellitus. International Journal of Research in Medical Sciences, 9(6), 1722–1730. https://doi.org/10.18203/2320-6012.ijrms20212242
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- https://www.semanticscholar.org/paper/Remogliflozin-Etabonate
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Published on: 17 Nov 2023 6:24 AM GMT