Review on Characteristics and Analytical Methods of Remogliflozin etabonate: An Update

: Hyperglycemia and its associated disorders like Diabetes mellitus are engulfing the world’s population at a faster pace. New-age medications like the SGLT 2 inhibitors have found their place in the run to combat DM. Drugs with these properties have proven to be effective in treating hyperglycemia, Obesity, and major Cardiac disorders. The interesting fact about these drugs is that they act independently of insulin levels in the patient’s body. The fact that they even bypass the side effects shown by currently used anti-diabetic medications has attracted the world’s hope to neutralize diabetes mellitus. The invention of Remogliflozin etabonate (RGE), an SGLT 2 inhibitor, has therefore added a silver lining to the gliflozin-family of drugs in the fight against DM. This is due to its least side effects as well as its effective mechanisms to treat hyperglycemia. It can be administered not only as a single entity but also can be co-administered in combination with other anti-hyperglycemic agents. RGE is already sold in the Indian market as REMO-ZEN, by Glenmark Pharmaceuticals. It has been studied thoroughly for its pharmacokinetic & pharmacodynamic profile. It is a benzylpyrazole glucoside. Various analytical methods have been formulated for its detection, quantification, and routine quality control activities. RGE can be studied with the help of UV-visible spectrophotometry, High-Performance Liquid Chromatography (HPLC) & Hyphenated techniques like Liquid Chromatography-Mass Spectroscopy (LC-MS/MS). This review briefs about overall chemical, pharmacological, pharmacokinetic & pharmacodynamics properties of RGE. It mainly discusses about various analytical techniques used for determining & estimating RGE.

Assessment of safety and tolerability of remogliflozin etabonate (GSK189075) when administered with total daily dose of 2000 mg of metformin

Background Patients with type 2 diabetes mellitus (T2DM) are characterized by an elevated glycemic index and are at a higher risk for complications such as cardiovascular disease, nephropathy, retinopathy and peripheral neuropathy. Normalization of glycemic index can be achieved by dosing combinations of metformin with other anti-diabetic drugs. The present study (Clintrials number NCT00519480) was conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of remogliflozinetabonate, an SGLT2 inhibitor, withdoses (500 mg and 750 mg BID) greater than the commercial dose (100 mg BID)in combination with metformin with minimum daily dose of 2000 mg given in two divided doses. Methods This was a randomized, double-blinded, repeat dose study in 50 subjects with T2DM. The study was conducted in three phases; run-in, randomization, and treatment. All subjects were on a stable metformin dosing regimen. Cohort 1 subjects were randomly allocated to receive either remogliflozin etabonate 500 mg BID or placebo BID (2:1) in addition to metformin. Cohort 2 subjects were administered with either remogliflozin etabonate 750 mg BID or placebo BID (2:1) in addition to metformin for 13 days. All the subjects were assessed for safety (adverse events, lactic acid levels, vital signs, electrocardiogram [ECG]), pharmacokinetic evaluation, and pharmacodynamics (Oral Glucose Tolerance Testing) parameters. Results Co-administration of remogliflozin etabonate and metformin was well tolerated in all subjects during the observation period. There were no severe or serious adverse events (SAEs) and no increase in lactic acid concentration was reported during the study. The statistical results showed that concomitant administration of remogliflozin etabonate, either 500 mg or 750 mg BID, with metformin had no effect on the pharmacokinetics of metformin. The accumulation ratios, Day 13 vs. Day 1, for AUC values of remogliflozin etabonate and its metabolites were all very close to 1, indicating no accumulation in plasma concentrations of remogliflozin etabonate and its metabolites. Mean glucose values from baseline and glucose and insulin values following oral glucose tolerance test (OGTT) were decreased in all treatment groups. Conclusion Co-administration of doses of remogliflozin etabonate (500 mg BID or 750 mg BID) greater than the commercial dose (100 mg BID) with metformin (2000 mg BID) was shown to be safe and effective during the observation period. Trial registration ClinicalTrials.gov, NCT00519480. Registered:22 August 2007.

A real-world clinical experience on the effectiveness of remogliflozin etabonate in management of Indian patients with type II diabetes mellitus

Background: The aim of the study was to evaluate effectiveness and safety of remogliflozin etabonate in a real-world outpatient setting in type 2 diabetes mellitus (T2DM) patients in India.Methods: A retrospective, observational, single-center study wherein medical records of adult patients (≥18 years old) with T2DM managed with remogliflozin 100 mg for at least three months at the diabetes care center in Jharkhand were retrieved. The effectiveness was assessed in terms of change from baseline in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), total body weight, blood pressure (BP, systolic and diastolic), kidney function tests, and lipid parameters after three months of treatment. Safety was assessed by adverse events (AEs) and serious AEs.Results: Half of the patients received ≥3 concomitant antidiabetic drugs, common being sulphonylureas (92%), and metformin (91%). Remogliflozin treatment resulted in a significant mean reduction from baseline in HbA1c [-1.99 (0.12%); p<0.001], FPG [-52.3 (4.31) mg/dl; p<0.001] and PPG [-103.6 (7.10) mg/dl; p<0.001). Bodyweight reduction was not statistically significant [-0.1 (10.12) kg]. A significant reduction was observed in the systolic BP [-15.9 (2.21) mmHg; p<0.001] and diastolic BP [-3.3 (0.95) mmHg; p=0.001]. Commonly reported AE was heartburn (51.4%) and urinary tract infections (34.2%). No serious AEs were reported. The mean estimated glomerular filtration rate showed a statistically significant reduction of -1.55 (0.61) ml/min. The lipid parameter findings were non-significant.Conclusions: The real-world experience of remogliflozin administered concomitantly with other antidiabetic drugs was effective and well-tolerated in Indian patients with T2DM.

Stability indicating thin-layer chromatographic method for estimation of antidiabetic drug Remogliflozin etabonate

Background A sensitive, precise, and stability-indicating high-performance thin-layer chromatographic (HPTLC) method has been developed for the analysis of Remogliflozin etabonate in tablet formulation. HPTLC plates precoated with silica gel 60 F254 were used as the stationary phase; methanol: ethyl acetate: toluene: NH3 (2:4:4:0.1, v/v/v) was used as mobile phase, and densitometry was used for the quantitative estimation of the drug. The proposed method was validated with respect to linearity, accuracy, precision, and robustness and applied for the estimation of drug in tablet dosage form. Results The Rf value of Remogliflozin etabonate was observed to be 0.61. The densitometric estimation was performed in reflectance mode at 229 nm. The method was found to be linear in the range of 500–8000 ng/band for Remogliflozin etabonate. The possible degradation pathway was estimated by performing forced degradation studies. The degradant peaks were well resolved from the drug peak with acceptable resolution in their Rf value. Conclusion An accurate and precise high-performance thin-layer chromatographic method has been developed for the quantification of Remogliflozin etabonate in tablets. Forced degradation studies were performed, and drug was found to be highly susceptible to acid, base hydrolysis, and oxidative stress degradation and gets converted into active drug Remogliflozin. Both Remogliflozin etabonate and Remogliflozin bands were well resolved. The method was applied for the analysis of drug in tablet formulation, and it can be used for routine quality control analysis, as well as for the analysis of stability samples.

Efficacy and safety of remogliflozin etabonate in type 2 diabetes mellitus patients in a tertiary care hospital

Background: Incidence and prevalence of diabetes have been steadily increasing with a raise of global prevalence about 8.5%. The major types of diabetes are differentiated by insulin deficiency versus insulin resistance. SGLT2 inhibitors are a new class of drugs that act by inhibiting glucose reabsorption in the proximal renal tubules. Remogliflozin a prodrug of remogliflozin, which is a potent and selective sodium-glucose co-transporter-2 inhibitor was used for the study. The objective of the study was to evaluate the efficacy and safety of Remogliflozin etabonate in reducing HbA1C and serum glucose in type II diabetics.Methods: This was a prospective observational study was done for 3 months. HbA1C, FBS and PPBS readings were noted and then the subjects were introduced to Remoglifozin 100 mg twice a day. At the end of 12 weeks HbA1C, FBS and PPBS were noted. The obtained data was analysed for its efficacy and safety.Results: The study included 22 male subjects and 28 females. Before Remoglifzoin was given the mean HbA1C level was 8.23± 0.798, mean FBS was 179± 29.79 and PPBS was 299.38± 24.21. Remoglifozin 100 mg was given and the mean HbA1C level was 7.52± 0.765, mean FBS was 166.30± 32.13 and mean PPBS was 249.46± 18.21. Post 3 months of Remoglifzoin induction a reduction in HbA1C, FBS and PPBS was seen.Conclusions: This study concludes Remoglifozin etabonate of 100 mg when given twice daily reduced the HbA1C levels, FBS and PPBS levels significantly.