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Abstract Aims The ICMR INDIAB-17 study revealed a diabetes prevalence of 11.4% in India, emphasizing the need for effective treatment for glycemic control. A Phase IV study was conducted to evaluate the safety and efficacy of a Fixed Dose Combination (FDC) of Remogliflozin, Metformin and Vildagliptin (RMV) in Type 2 Diabetes Mellitus (T2DM) patients uncontrolled on Metformin plus SGLT2 inhibitor or Metformin plus DPP4 inhibitor dual therapy. Methods A total of 215 patients (mean age: 46.4 years; 64% male, 36% female) were enrolled across multiple centers in India. The study population included patients with a baseline HbA1c ≥ 8% at the time of screening. The primary objective was to assess safety based on treatment-emergent adverse events (TEAEs), while the secondary. aim was to evaluate effectiveness in terms of glycemic (HbA1c, fasting plasma glucose, postprandial glucose) and extra-glycemic measures (renal and lipid parameters). Statistical analysis was conducted using paired t-tests and the Wilcoxon signed-rank test for within-group comparisons, and the Bonferroni correction was applied to adjust for multiple comparisons. Effectiveness was evaluated at baseline, week 12, and week 24. Results The study demonstrated statistically significant reductions in mean HbA1c levels from baseline to both week 12 and week 24 (p

Objectives: This study aimed to evaluate the safety and efficacy of remogliflozin compared to vildagliptin as an add-on drug to metformin in type 2 diabetes mellitus (T2DM) treatment. Metformin is considered a first-line drug in T2DM. However, as the disease progresses with heightened insulin resistance and declining β-cell function, the use of metformin alone is often inadequate to achieve optimum glucose levels. Methods: This prospective, randomised study was conducted at Maulana Azad Medical College and Associated Hospital in New Delhi, India, between February 2020 to January 2021. This study recruited 60 T2DM patients aged 35–70 years with glycated haemoglobin (HbA1c) >6.5% taking metformin at a daily dosage of 1,500–3,000 mg for ≥3 months. Patients were randomly assigned in a 1:1 ratio to receive either vildagliptin (50 mg) or remogliflozin (100 mg) twice daily for 90 days. The primary endpoint was a change in HbA1c levels from baseline to the end of 90 days whereas secondary endpoints were changes in lipid profile and weight. Results: The decrement in mean HbA1c levels was significantly higher in the remogliflozin group than in the vildagliptin group (−8.1% versus −2.4%; P <0.001). In addition, more significant weight loss was found in remogliflozin-treated patients (−5.2% versus −0.6%; P <0.01). Both treatments were well tolerated throughout the study. Conclusion: Compared to vildagliptin, remoglilflozin was significantly more effective in glycaemic control and weight loss in patients with T2DM and can therefore be considered as an add-on drug in T2DM not adequately controlled by metformin monotherapy. [ABSTRACT FROM AUTHOR]

Abstract To estimate remogliflozin, vildagliptin and metformin in a new fixed dose combination two chromatographic methods were developed and validated. The initial method is a green RP- HPLC method which uses a (150 × 4.6) mm, 2.7 mm C18 column, Ascentis as stationary phase for chromatographic separation and mobile phase made up of acetonitrile (ACN) and phosphate buffer in a ratio of 35:65 by volume. A PDA detector was used for quantification at 220 nm. 1.5 mL/min is the flow rate. Linearity was observed at 62.5–375 µg/mL, 6.25–37.5 µg/mL and 12.5–75 µg/mL for remogliflozin, vildagliptin and metformin respectively. A subsequent technique developed is HPTLC densitometric method which was also found as greener method for the separation and quantification of the three analytes in which pre-coated silica gel 60F254 aluminum plates were taken as stationary phase and the mobile phase contain phosphate buffer: ACN: glacial acetic acid in the ratio of 3: 7: 0.2 by volume. The densitometric measurements were achieved at a wavelength of 205 nm. Linearity was observed at concentrations 200–600 ng/spot, 20–60 ng/spot, 40–120 ng/spot for metformin, vildagliptin and remogliflozine respectively. Mean % recovery was 98.92–100.41% for remogliflozin, 99.92–100.33% for vildagliptin and 99.17–100.19% for metformin. The method was tested precise, specific and robust. [ABSTRACT FROM AUTHOR]

Remogliflozin and Vildagliptin are the latest drug combination in order to treat type 2 diabetes. The present work describes a comparative study of 2nd-ordered derivative UV and isocratic stability indicating RP-HPLC methods for simultaneous determination of Remogliflozin and Vildagliptin in the drug and its formulation. The HPLC method was established with a C18 column and the mobile phase with Buffer (pH-6.50): Acetonitrile: Methanol ratio of 55:44:1, at 1.2 ml/min flow and wavelength of 210 nm. The UV spectrophotometric method works on spectrophotometry with 2nd order derivative spectra(2D) using a zero-line cross method. The absorbance determination was performed at 246.0 nm for REM and at 219 .6 nm for VIL. The methods were validated for Linearity, Precision, Recovery, Robustness, and Forced degradation as per ICH-Q2(R1). The linear range was established in the range of 4-80 ppm for REM and 2-40 ppm for VIL for the UV method and 2-200 ppm for REM and 1-100 ppm for VIL for the HPLC method with regression coefficient =0.990. The accuracy was 99.37% & 99.62% for UV and 100.98 & 100.65 for the HPLC method for REM and VIL respectively. The proposed methods have been effectively used for the quantification of REM and VIL in API mixture and formulation dosage forms. Both methods are economical, fast, simple, and accurate which can be easily adopted for laboratory use. [ABSTRACT FROM AUTHOR]

Abstract 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.

Background and Aims: Remogliflozin is a new addition to class of Sodium Glucose Cotransporter-2 (SGLT-2) inhibitors available in India. The drug is introduced and marketed at a lower price range as compared to other gliflozins. Remogliflozin is expected to gain preference over other gliflozins as it is cheaper. However, the pragmatic value of remogliflozin in establishing and maintaining blood glucose control is yet to be established. This objective of this study was to establish the efficacy of remogliflozin in maintaining glycemic control in patients of T2DM when switching from other gliflozins.Methods: The study was conducted for a duration of four months in 159 diabetic patients, previously on combination of one gliflozin and other anti-hyperglycaemic agents. Patients were prescribed remogliflozin with instructions to not modify their dietary practices. Pre- and post-remogliflozin switch levels of conjugated haemoglobin were used to ascertain the effect of the drug on patients.Results: The mean pre- and post-remogliflozin switch HbA1c levels were found to be significantly different (p

A rapid and reproducible hydrophilic liquid chromatography (HILIC) process was established for concomitant determination of remogliflozin etabonate (RE), vildagliptin (VD), and metformin (MF) in a formulation. A face-centered central composite experimental design was employed to optimize and predict the chromatographic condition by statistically studying the surface response model and design space with desirability close to one. A HILIC column with a simple mobile phase of acetonitrile (65% v/v) and 20 mM phosphate buffer (35% v/v, pH 6, controlled with orthophosphoric acid) was used to separate RE, VD, and MF. RE, VD, and MF were separated in 3.6 min using an isocratic mode mobile phase flow at a flow rate of 1.4 mL at room temperature, and the analytes were examined by recording the absorption at 210 nm. The developed HILIC method was thoroughly validated for all parameters recommended by ICH, and linearity was observed in the ranges 20–150 µg/mL, 10–75 µg/mL, and 50–750 µg/mL for RE, VD, and MF, respectively, along with excellent regression coefficients (r2 > 0.999). The calculated percentage relative deviation and relative error ascertained the precision and accuracy of the method. The selectivity and accuracy were further confirmed by the high percentage recovery of added standard drugs to the formulation using the standard addition technique. The robustness of the HILIC processes was confirmed by developing a half-normal probability plot and Pareto chart, as the slight variation of a single factor had no significant influence on the assay outcomes. Utilization of the optimized HILIC procedure for concurrent quantification of RE, VD, and MF in solid dosage forms showed accurate and reproducible results. Hence, the fast HILIC method can be regularly employed for the quality assurance of pharmaceutical preparations comprising RE, VD, and MF. [ABSTRACT FROM AUTHOR]

Background: For the treatment of diabetes mellitus type 2, a new formulation containing vildagliptin and remogliflozin was developed. A simple and rapid RP-HPLC method employing linagliptin as an internal standard was developed for quality control of this medicine. Methodology: Formulation analytes, including IS, were separated on a Zorbax C18 column with isocratic elution of acetonitrile and phosphate buffer (pH 5) 55:45 v/v at a flow rate of 1.2 mL/min. The experiment was carried out at room temperature and monitored at a wavelength of 210 nm. The approach was also validated in accordance with the ICH Q2 requirements. Results: The optimized HPLC approach revealed a satisfactory linearity in the concentration ranges of 10-60 µg/mL and 10-100 µg/mL for VIL and REM respectively, with good regression coefficient ( R2≥0.998). The average accuracy for VL and REM was 99.57 percent and 100.59 percent, respectively, with a low percentage relative error. The method's precision was proven by the low percentage relative standard deviation. Furthermore, a robustness assessment employing a Pareto chart generated using a three-level factor interaction study, a multivariate technique, demonstrated that minor changes in individual experimental conditions had no effect on the test results. Finally, the optimized HPLC method was effectively used to assess VIL and Rem from formulation simultaneously. Conclusion: The findings of an assay comparing a simple and rapid isocratic RP-HPLC method devised for the simultaneous quantification of VIL and REM to a previously published approach revealed no significant differences in the assay results. As a result, it might be utilized in any analytical laboratory for quality control of this formulation. [ABSTRACT FROM AUTHOR]

Viswanathan Mohan,1 Ambrish Mithal,2 Shashank R Joshi,3 SR Aravind,4 Subhankar Chowdhury5 1Madras Diabetes Research Foundation & Dr. Mohan’s Diabetes Specialties Centre, Chennai, Tamil Nadu, India; 2Endocrinology and Diabetology, Max Healthcare Hospital, Gurgaon, India; 3Joshi Clinic, Lilavati Hospital, Apollo Sugar Clinic and Bhatia Hospital, Mumbai, India; 4Diacon Hospital, Bengaluru, India; 5Deptartment of Endocrinology, IPGME&R and SSKM Hospital, Kolkata, IndiaCorrespondence: Viswanathan Mohan Tel +91 44 4396 8888Fax +91 44 2835 0935Email drmohans@diabetes.ind.inAbstract: Type 2 diabetes mellitus (T2DM) is an emerging epidemic in Asian countries, especially in India. With the advent of the SGLT2 inhibitor class of drugs demonstrating benefits beyond glycemic control, viz. weight loss, blood pressure reduction, and cardiovascular and renal protection, the management of T2DM has taken a quantum leap. Remogliflozin etabonate (RE) is the latest addition to the SGLT2 inhibitor class of drugs that have been recently approved in India for the management of T2DM. RE is a potent and selective inhibitor of SGLT2 with the unique distinction of being administered as a prodrug, existence of active metabolites, and short half-life necessitating twice-daily dosing. The Phase III study of RE demonstrated it to be an efficacious and safe agent and non-inferior to the currently available SGLT2 inhibitors. This paper reviews not only the pharmacokinetics, pharmacodynamics, clinical efficacy, and safety profile of RE but also its molecular and clinical development program. This review has taken into consideration all available published as well as unpublished literature on RE and discusses the individual studies performed during its development for characterization of pharmacological profile.Keywords: remogliflozin, etabonate, SGLT2 inhibitor, design, development, place in therapy, T2DM

Background: An anti-diabetic formulation consisting of vildagliptin and remogliflozin was prescribed for better glycemic control. In the present study a simple, rapid derivative spectrophotometric methods were evolved to analyze these two analytes from the formulations. Methods: Two processed UV spectrophotometric methods were established by measuring the peak amplitude at zero-crossing of second derivative spectra of analytes. The second procedure comprehends the generation of zero - order spectra from the mixture of analyte spectra by division and multiplication by the pure analyte spectra to remove the effect of one of the analytes. Results: Both methods showed linearity concentrations in the range of 2-75 µg/ml for RGF and 2-50 µg/ml for VGT. The low LOD and LOQ found for RGF and VGT by both methods indicated the good sensitivity of the methods. The mean percentage recovery was 98.60 % and 100.78%, for RGF and 98.81 % and 99.15 % for VGT, with low percent relative error. The % RSD for intra and inter-day precision was less than ±2%. Finally, the planned methods were employed for the assay of the VGT and RGF from the medicine and the outcomes were matched with the reported methods. Conclusion: The assay results of the formulation were in agreement with the concentration of labeled amount and no significant difference was observed in the results when compared to the reported method. Hence, the anticipated procedures could be applied for the routine quality control of formulations consisting of VGT and RGF. [ABSTRACT FROM AUTHOR]

SGLT-2 inhibitors have recently emerged as an important class of oral drugs for treatment of type 2 diabetes mellitus, especially in patients with cardiovascular or renal impairment, recommended in all recent treatment guidelines. They have additional advantages of weight and blood pressure reduction but also pose problems like genitourinary infections. These drugs generally have a high cost making affordability a major consideration in their prescription in developing countries like India. A new molecule remogliflozin has been approved in India in 2019 after a phase 3 trial proved its efficacy and safety in comparison to dapagliflozin. This drug has been priced substantially lower than other SGLT-2 inhibitors, and despite the disadvantage of twice daily administration, it potentially reduces treatment cost to less than half compared to other molecules of this class. With a good tolerability profile on the basis of available safety data till date, remogliflozin could be a useful alternative for providing SGLT-2 inhibitor therapy in a country like India where out of pocket expenses for drug acquisition matter significantly for the general population. However, long term safety and efficacy data especially on cardiovascular and renal outcomes are currently lacking for the drug. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: A selective and novel method has been optimized for the evaluation of remogliflozin and metformin hydrochloride in bulk and in the formulation and cleaning of samples by UPLC-PDA in bulk and formulation and product traces. Materials and Methods: The principle analytes were eluted with phosphate buffer (pH: 4.5): acetonitrile (60:40%, v/v) as the mobile phase using the Spherisorb C18, 5 µm, 4.6 mm x 150 mm analytical column with a 1.0 mL/min flow rate and a 10 µiL sample volume at 245 nm in a photodiode array detector. Results: The retention times of remogliflozin and metformin hydrochloride were 3.017 min and 5.011 min with a total run time of 8 min. The curve indicates that the correlation coefficient (r²) was superior with a value of 1.000 in the linear range of 10 ng/mL-100.0 ng/mL for remogliflozin and 50 ng/mL-500.0 ng/mL for metformin hydrochloride. The correlation coefficient (r²) for metformin hydrochloride was found to be 1.000. The lower limits of quantification and detection for remogliflozin and metformin hydrochloride were found to be 10 ng/mL and 50 ng/mL, and 5 ng/mL and 10 ng/mL, respectively. Conclusion: The developed method was validated and applied to the bulk drug estimation and drug formulation and cleaning samples. All the results obtained with this method was accurate and precise. [ABSTRACT FROM AUTHOR]

For the treatment of diabetes mellitus, a new formulation containing remogliflozin etabonate (REMO) and metformin HCl (MET) has recently been approved. This study is aimed to develop simple and quick RP-UHPLC methods for measuring REMO and MET simultaneously. REMO and MET chromatographic separation were carried out on a Zorbax Eclipse Plus C18 (150×4.6 mm, 5 µm) column with acetonitrile: phosphate buffer (pH: 3) (60:40 %, v/v) mobile phase, 10 µl sample volume and 1.0 ml/min flow rate at 230 nm in a diode array detector. REMO had a 99.51 % average percent assay, while MET had a 99.60 % average percent assay. The methods projected were simple, precise, accurate, and fast. They can also be used to verify the consistency of REMO and MET formulations regularly. [ABSTRACT FROM AUTHOR]

Remogliflozin is a novel SGLT-2 inhibitor used for the management of Type 2 Diabetes Mellitus (T2DM). Since its introduction medical literature is scarce on its quantitative effects. We performed this meta-analysis to ascertain its safety and efficacy in the treatment of T2DM. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook, six studies involving 1,605 participants were analyzed. Our analysis found comparable reductions in glycated hemoglobin (HbA1c) by remogliflozin in comparison to the comparators. It was found to be inferior to other anti-diabetic drugs in decreasing fasting plasma glucose and post-prandial glucose. A significant reduction was obtained in body weight and a significant increase was also found in high-density lipoprotein cholesterol (HDL-C) levels. Remogliflozin did not significantly increase the risk for total adverse events, severe adverse events, or hypoglycemic episodes. The results were accompanied by high heterogeneity, which necessitates conducting high-quality randomized control trials for more robust evidence synthesis. Overall Remogliflozin can be considered a safe drug with beneficial effects on body weight and HDL-C levels for the treatment of people with T2DM., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tewari et al.)

Background: The result of pharmaceutical industry research for the new class and the new combination of drugs for the treatments of diabetes is the newly approved combination of metformin (MET) and remogliflozin (REM). For the quality control of this formulation, three smart, reproducible and non-sophisticated spectroscopic techniques were developed by modification of UV spectra. Materials and Methods: The first two methods were based on the measurements of the peak height of the third derivative and second derivative ratio spectra of MET and REM and the third method was the constant center spectrum subtraction method. Results: The proposed methods exhibited Beer's law in the range of 2.5 to 30 ìg/ml and 1 to 24 ìg/ml for MET and REM correspondingly by all three methods. The mean percentage recovery was found to be in the range of 99.08% to 100.15% for MET and 98.73% to 100.27% for REM. Further, both analytes were quantified from the formulation using proposed spectroscopic methods with high accuracy. Comparison of all three methods with the reported HPLC method showed no variation in the assay outcomes in relation to accuracy and precision. Conclusion: The suggested techniques are simple, accurate and reproducible, hence could be used for regular quality control of formulation consisting of MET and REM. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop a fast RP-HPLC method for simultaneous measurement of two antidiabetic formulations (vildagliptin + remogliflozin and teneligliptin + remogliflozin) under identical experimental conditions. Using the Box–Behnken approach and response surface design, the interaction and quadratic influence of three variable parameters, acetonitrile %, pH of the mobile phase, and flow rate, on resolution between the peaks were optimized. To forecast the resolution of peaks (2.7 and 6.5) for the three anti-diabetic medications, the design space with desirability function was used to find the optimal chromatographic conditions. Isocratic elution with 58:42 acetonitrile and phosphate buffer (20 mM KH2PO4, pH adjusted to 4.9 with orthophosphoric acid) over a Zorabx C18 HPLC column with a flow rate of 1.2 mL min−1 separated all three analytes in 2.5 min. In addition, the optimized HPLC process was validated using ICH recommendations. The devised HPLC method’s precision and accuracy were proven by the low percent relative standard deviation (0.60–1.65%), good percentage recovery (98.18–101.50%), and low percentage relative errors (0.20–1.82%). The method’s robustness was also proven by slightly varying the five separate parameters. Finally, the accuracy of the proposed HPLC approach was confirmed using a standard addition method for simultaneous determination of vildagliptin + remogliflozin and teneligliptin + remogliflozin from formulations. Furthermore, the findings demonstrated that experimental design can be successfully used to optimize chromatographic conditions with fewer runs. The devised HPLC method for simultaneous quantification of two binary combinations utilizing the same chromatographic conditions is fast, accurate, precise, and easy, and it might be utilized in laboratories for routine quality control investigations on both formulations.

Three rapid, accurate, and ecofriendly processed spectrophotometric methods were validated for the concurrent quantification of remogliflozin (RGE) and vildagliptin (VGN) from formulations using water as dilution solvent. The three methods developed were based on the calculation of the peak height of the first derivative absorption spectra at zero-crossing points, the peak amplitude difference at selected wavelengths of the peak and valley of the ratio spectra, and the peak height of the ratio first derivative spectra. All three methods were validated adapting the ICH regulations. Both the analytes showed a worthy linearity in the concentration of 1 to 60 µg/mL and 2 to 90 µg/mL for VGN and RGE, respectively, with an exceptional regression coefficient (r2 ≥ 0.999). The developed methods demonstrated an excellent recovery (98.00% to 102%), a lower percent relative standard deviation, and a relative error (less than ±2%), confirming the specificity, precision, and accuracy of the proposed methods. In addition, validated spectrophotometric methods were commendably employed for the simultaneous determination of VGN and RGE from solutions prepared in the laboratory and the formulation. Hence, these methods can be utilized for the routine quality control study of the pharmaceutical preparations of VGN and RGE in pharmaceutical industries and laboratories. The ecofriendly nature of the anticipated spectrophotometric procedures was confirmed by the evaluation of the greenness profile by a semi-quantitative method and the quantitative and qualitative green analytical procedure index (GAPI) method.

Objective: To review phase 3 trials of sodium-glucose cotransporter (SGLT) inhibitors in type 1 diabetes mellitus (T1DM) patients. Data Sources: A literature search of Ovid MEDLINE databases (1946 through May 17, 2019) limited to English-language human clinical trials was conducted using the following terms: sodium-glucose transporter 2 inhibitors, canagliflozin, dapagliflozin, empagliflozin, sotagliflozin, ertugliflozin, ipragliflozin, or remogliflozin combined with type 1 diabetes mellitus. Results were verified via Google Scholar and clinicaltrials.gov. Study Selection and Data Extraction: Articles were included if they were phase 3 trials in adults with T1DM. Data Synthesis: Phase 3 trials are available for dapagliflozin, empagliflozin, and sotagliflozin. All 3 drugs demonstrated statistically significant reductions in hemoglobin A1C, weight, and total daily insulin dose without an increased risk of hypoglycemia in up to 52 weeks of therapy. The incidence of diabetic ketoacidosis (DKA) was higher in patients on a SGLT inhibitor at all doses, with the exception of empagliflozin 2.5 mg (0.8% vs 1.2% with placebo). Relevance to Patient Care and Clinical Practice: SGLT inhibitors are potential adjuncts to insulin in T1DM patients, providing clinically meaningful benefits. Regulatory bodies have either approved or are reviewing these agents for use in T1DM. Clinicians should be familiar with the DKA risk associated with SGLT inhibitors and utilize DKA risk-mitigation strategies. Empagliflozin 2.5 mg warrants additional investigation given its efficacy without an increased incidence of DKA. Conclusions: Phase 3 trial data of SGLT inhibitors provide evidence for sustained efficacy in T1DM patients. Appropriate patient selection for therapy and routine monitoring are essential to minimize associated risks. [ABSTRACT FROM AUTHOR]

Recently, a new formulation containing metformin HCl (MFH) and remogliflozin etabonate (RGE) has been approved for the management of diabetes mellitus. However, only one analytical method has been reported for the simultaneous determination of both the analytes. Therefore, the current study was designed to develop simple UV derivative spectroscopic and rapid RP-HPLC methods for simultaneous determination of MFH and RGE. The chromatographic separation of MFH and RGE was performed using a monolithic C18 column with an optimized chromatographic conditions carried out by full factorial Box–Behnken design model. The spectroscopic technique was based on the determination of peak amplitude of second-order derivative UV spectra at zero crossings. Further, both the methods were validated and compared statistically using Student’s-t-test and F-test, and employed for the concurrent estimation of MFH and RGE in laboratory mixed solutions and formulations. Perturbation plots and response surface models showed the effect of chromatographic parameters and the final chromatographic condition was selected from 47 solutions suggested by the desirability function. Further, UV spectroscopic and HPLC procedures showed good linearity in the range of 1–24 µg/mL and 2–150 µg/mL for RGE and 2–30 µg/mL and 5–200 µg/mL for MFH, respectively. The average percent assay was found to be 99.51% and 99.80% for MFH and 99.60% and 100.07% for RGE by spectroscopic and HPLC methods, respectively. The proposed methods were simple, accurate, precise, and rapid. Therefore, they can be used for regular quality control of MFH and RGE formulations and dissolution studies as well.

1. Several sodium-glucose cotransporter-2 (SGLT-2) inhibitors are in clinical use for the management of type 2 diabetes. The objectives of the current review were: (a) to provide a comparative pharmacokinetics including absorption, distribution, metabolism and excretory (ADME) profiles of three SGLT-2 inhibitors namely: sergliflozin, remogliflozin and ertugliflozin; (b) to provide some perspectives on possible developmental issues. 2. Based on the half-life (t1/2) values observed in humans, the rank order of the three SGLT-2 inhibitors was ertugliflozin (16 h) > remogliflozin (2–4 h) > sergliflozin (1–1.5 h). Therefore, while once a day dosing of ertugliflozin is possible, the other two drugs need to be dosed more frequently. Perhaps, the shortt1/2of sergliflozin may have contributed for its discontinuation. 3. Although there was paucity of published data on the metabolism, transporter related and excretory aspects for sergliflozin, the other two drugs provided a differentiating profile. However, the compiled data suggested that there may be a minimal or no risk of pharmacokinetic drug interaction issues associated with any of the reviewed drugs. 4. Because of the crowded development pipeline and approved SGLT-2 inhibitors, the safety and efficacy of sergliflozin, remogliflozin and ertugliflozin appear to be a key from differentiation perspective. [ABSTRACT FROM AUTHOR]

The major trials, e.g., EMPA-REG OUTCOME, CANVAS, and CREDENCE, showed the renal and cardiovascular benefit of sodium-glucose transport protein 2 (SGLT2) inhibitors. The SGLT2 inhibitors, Empagliflozin, Dapagliflozin, and Canagliflozin, have shown no significant adverse renal effects. Still, our patients with type 2 diabetes on Remogliflozin, a type of SGLT2 inhibitor approved in India for the treatment of diabetes, seems to cause acute tubular necrosis as confirmed by clinical and pathological evidence in our study. The two critical findings in our research include a consistent rise in hs-CRP and a pathologist's biopsy report, excluding other causes. Therefore, we need sizeable cardiovascular-renal outcome trials to ascertain the safety of Remogliflozin in future studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Jain et al.)

ABSTRACT Remogliflozin etabonate (RE) is the prodrug of remogliflozin (R), an inhibitor of renal glucose transport designed to reduce blood glucose concentrations for the treatment of type 2 diabetes. This open-label, randomized, single-dose, four-way crossover study, (with one add-on arm) in eight healthy men evaluated the regional gastrointestinal absorption of RE, the systemic appearance of the active entity R, and an active metabolite, GSK279782. The InteliSite® Companion Capsule was used to administer a single dose of RE 100 mg to the mid-small intestine or cecum/colon. Oral administration of the IR tablet of RE showed similar bioavailability of R compared with small intestine delivery with both suspension and solution. The lowest bioavailability of remogliflozin was found with large intestine delivery and therefore not a suitable region for prodrug delivery. Although both lower permeability and decreased ester hydrolysis of remogliflozin etabonate in the colon can explain reduced plasma exposures of remogliflozin, the data suggest relatively limited remogliflozin etabonate hydrolysis in the colon and provides evidence for a diminishing gradient of esterase activity from small to large intestine. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The incidence of type 2 diabetes mellitus is increasing worldwide. The existing therapeutic classes of antidiabetic drugs are not adequately effective in maintaining long-term glycemic control in most patients, even when used in combination. One emerging novel therapeutic class of antidiabetic drugs is sodium glucose cotransporter 2 (SGLT2) inhibitors. SGLT2 accounts for 90% of the glucose reabsorption in the kidney. The SGLT2 inhibitors increase urinary excretion of glucose and lower plasma glucose levels in an insulin-independent manner. Dapagliflozin, the most prominent molecule in this class, is currently in a phase III clinical trial. Other members of this class (eg, sergliflozin, remogliflozin) are also in different phases of clinical trials. This class of novel agents can effectively control blood sugar level without producing weight gain or hypoglycemia. Results of ongoing phase III clinical trials are crucial to determine whether the risk-benefit ratio will allow approval of this new class of drugs for the management of type 2 diabetes mellitus. [ABSTRACT FROM PUBLISHER]

The aim of this study was to develop a fast RP-HPLC method for simultaneous measurement of two antidiabetic formulations (vildagliptin + remogliflozin and teneligliptin + remogliflozin) under identical experimental conditions. Using the Box–Behnken approach and response surface design, the interaction and quadratic influence of three variable parameters, acetonitrile %, pH of the mobile phase, and flow rate, on resolution between the peaks were optimized. To forecast the resolution of peaks (2.7 and 6.5) for the three anti-diabetic medications, the design space with desirability function was used to find the optimal chromatographic conditions. Isocratic elution with 58:42 acetonitrile and phosphate buffer (20 mM KH2PO4, pH adjusted to 4.9 with orthophosphoric acid) over a Zorabx C18 HPLC column with a flow rate of 1.2 mL min−1 separated all three analytes in 2.5 min. In addition, the optimized HPLC process was validated using ICH recommendations. The devised HPLC method's precision and accuracy were proven by the low percent relative standard deviation (0.60–1.65%), good percentage recovery (98.18–101.50%), and low percentage relative errors (0.20–1.82%). The method's robustness was also proven by slightly varying the five separate parameters. Finally, the accuracy of the proposed HPLC approach was confirmed using a standard addition method for simultaneous determination of vildagliptin + remogliflozin and teneligliptin + remogliflozin from formulations. Furthermore, the findings demonstrated that experimental design can be successfully used to optimize chromatographic conditions with fewer runs. The devised HPLC method for simultaneous quantification of two binary combinations utilizing the same chromatographic conditions is fast, accurate, precise, and easy, and it might be utilized in laboratories for routine quality control investigations on both formulations. [ABSTRACT FROM AUTHOR]

No meta-analysis has analysed efficacy and safety of remogliflozin. We undertook this meta-analysis to address this gap in knowledge Electronic databases were searched for RCTs involving diabetes patients receiving remogliflozin as compared to controls. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glycaemia, lipids and adverse events. Data from 3 RCTs involving 535 patients was analysed [2 having pioglitazone and 1 having dapagliflozin as active comparator]. Over 12–24 weeks use, Hba1c [mean difference (MD) −0.13% (95% CI: 0.35 – 0.09%); P = 0.24; I2 = 99%] and fasting glucose [MD 3.67 mg/dl (95% CI: 0.53 – 7.88 mg/dl); P = 0.09; I2 = 52%]. reduction with remogliflozin was not significantly different from controls. Remogliflozin was inferior to dapagliflozin with regards to reduction in post-prandial glucose [MD+12.17 mg/dl (95%CI:10.79–13.55 mg/dl); P < 0.001].Remogliflozin use was associated with a significantly greater decline in body weight [MD -2.79 kg (95% CI: 3.07 to −2.51 kg); P < 0.001; I2 = 30%]. Total adverse events [Risk ratio (RR) 1.21 (95% CI: 0.62–2.64); P = 0.58; I2 = 59%] were comparable among groups. Remogliflozin had HbA1c and fasting glucose reduction comparable to pioglitazone and dapagliflozin. The paradox with regard to post-prandial glucose reduction needs further evaluation. The current analysis is limited by considerable data heterogeneity and low certainty of evidence for most primary and secondary outcomes. There remains urgent need for high quality RCTs evaluating long-term outcomes with remogliflozin. • Data from three studies (535 patients) was analysed to evaluate efficacy and safety of remogliflozin. • Remogliflozin had similar HbA1c and fasting glucose reduction compared to pioglitazone and dapagliflozin. • Remogliflozin was inferior to dapagliflozin with regards to reduction in post-prandial glucose. • Remogliflozin use was associated with weight loss, an observation which was accentuated due to use of pioglitazone in the control group. • Remogliflozin is lipid neutral with no significant changes in total cholesterol, LDL-C and HDL-C levels. [ABSTRACT FROM AUTHOR]

Three rapid, accurate, and ecofriendly processed spectrophotometric methods were validated for the concurrent quantification of remogliflozin (RGE) and vildagliptin (VGN) from formulations using water as dilution solvent. The three methods developed were based on the calculation of the peak height of the first derivative absorption spectra at zero-crossing points, the peak amplitude difference at selected wavelengths of the peak and valley of the ratio spectra, and the peak height of the ratio first derivative spectra. All three methods were validated adapting the ICH regulations. Both the analytes showed a worthy linearity in the concentration of 1 to 60 µg/mL and 2 to 90 µg/mL for VGN and RGE, respectively, with an exceptional regression coefficient (r2 ≥ 0.999). The developed methods demonstrated an excellent recovery (98.00% to 102%), a lower percent relative standard deviation, and a relative error (less than ±2%), confirming the specificity, precision, and accuracy of the proposed methods. In addition, validated spectrophotometric methods were commendably employed for the simultaneous determination of VGN and RGE from solutions prepared in the laboratory and the formulation. Hence, these methods can be utilized for the routine quality control study of the pharmaceutical preparations of VGN and RGE in pharmaceutical industries and laboratories. The ecofriendly nature of the anticipated spectrophotometric procedures was confirmed by the evaluation of the greenness profile by a semi-quantitative method and the quantitative and qualitative green analytical procedure index (GAPI) method. [ABSTRACT FROM AUTHOR]

The recent trend in green analytical chemistry is the development of green analytical methods using environmentally friendly solvents. Therefore, three ecofriendly manipulated UV spectroscopic techniques have been validated for the concurrent quantification of newly approved remogliflozin etabonate (REM) and metformin HCl (MET) tablets using water as a solvent. The first method was established using first derivative absorption spectroscopic method by determining the peak amplitude at 233.0 nm for REM and 252.2 nm for MET, a zero crossing of one the component. The second and third methods were based on the peak amplitude difference and first-order derivative absorption of the ratio spectra developed by the manipulation of scanned UV spectra. REM and MET showed good linearity in the series of 1-20 µg ml -1 and 2.5-35 µg ml -1 , respectively, by all three methods with an excellent correlation coefficient (r 2 ≥ 0.998). Further, the proposed UV spectroscopic techniques were validated as per International Council for Harmonization guidelines. The methods showed good sensitivity, accuracy, and precision. Anticipated procedures were effectively utilized for the concurrent quantification of REM and MET in laboratory prepared mixtures and tablets. The high percent recovery with low standard deviation found for both analytes by all three methods confirms the accuracy and precision of the procedures. Finally, the greenness of the proposed spectroscopic methods, evaluated by semi-quantitative and quantitative methods, showed the eco-friendly nature of the methods. Furthermore, the proposed approaches were simple, accurate, sensitive, economic, and environmentally friendly and hence can be utilized for regular quality control of REM and MET formulation.

Aims & Objectives: The objective of this retrospective study was to investigate the efficacy of adding remogliflozin to current insulin glargine plus two oral drug i.e. metformin and teneligliptin therapy in poorly controlled Indian type 2 diabetes., Materials and Methods: 173 study participants were initially selected from patient database who continued on their insulin glargine or received an increased dose of insulin glargine along with other OHA based therapy (Group A) and 187 were selected who had received remogliflozin (100 mg BD) (Group B) in addition to insulin glargine along with other OHA based therapy. Glycated haemoglobin (HbA1c), total daily insulin dose, body weight, and the number of hypoglycemic events were recorded at weeks 0, 12 and 24., Results: During the study, mean values of HbA1c, FBG and P2BG were significantly reduced in both groups. Insulin requirements decreased from 45.8 ± 16.7 IU/day to 38.5 ± 13.5 IU/day at week 12 (P < 0.001) and at week 24 even further decreased to 29.5 ± 14.5 IU/Day. Twenty three patients in group B were able to cease insulin treatment altogether after 24 week treatment. It has been observed that to attain tight blood glucose control, we need to increase insulin dose in group A from 45.5 ± 16.5 IU/Day to 51.5 ± 14.5 at week 12 (P<0.01), which further increased to 53.8 ± 12.8 IU/Day at week 24 (P<0.01). Adding remogliflozin showed significant effect on blood pressure (P < 0.001) and weight reduction (P < 0.001). It has been observed that 38% patients achieved targeted HbA1c (≤7%) in group B where it was 22% in group A., Conclusion: Results demonstrate that in uncontrolled T2DM patients, remogliflozin 100 mg BD can successfully lay a foundation for prolonged good glycemic control. Early addition of remogliflozin with insulin glargine plus OHAs may be an alternative compared to intensive up titration of insulin daily dose in people with uncontrolled T2DM., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)