remogliflozin-etabonate and Diabetes-Mellitus--Type-2

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (gliflozins) represent the most recently approved class of oral antidiabetic drugs. SGLT-2 overexpression in diabetic patients contributes significantly to hyperglycemia and related complications. Therefore, SGLT-2 became a highly interesting therapeutic target, culminating in the approval for clinical use of dapagliflozin and analogues in the past decade. Gliflozins improve glycemic control through a novel insulin-independent mechanism of action and, moreover, exhibit significant cardiorenal protective effects in both diabetic and nondiabetic subjects. Therefore, gliflozins have received increasing attention, prompting extensive structure-activity relationship studies and optimization approaches. The discovery that intestinal SGLT-1 inhibition can provide a novel opportunity to control hyperglycemia, through a multifactorial mechanism, recently encouraged the design of low adsorbable inhibitors selectively directed to the intestinal SGLT-1 subtype as well as of dual SGLT-1/SGLT-2 inhibitors, representing a compelling strategy to identify new antidiabetic drug candidates.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemic Agents; Sodium; Sodium-Glucose Transporter 2 Inhibitors

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 and 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) and Hyphenated techniques like Liquid Chromatography- Mass Spectroscopy (LC-MS/MS). This review briefs about the overall chemical, pharmacological, pharmacokinetic and pharmacodynamics properties of RGE. It mainly discusses various analytical techniques used for determining and estimating RGE.

Topics: Chromatography, Liquid; Diabetes Mellitus, Type 2; Glucosides; Humans; Hyperglycemia; Hypoglycemic Agents; Pyrazoles; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Tandem Mass Spectrometry

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.

Topics: Diabetes Mellitus, Type 2; Drug Development; Glucosides; Humans; Hypoglycemic Agents; Pyrazoles; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

Remogliflozin, a selective sodium-glucose co-transporter subtype 2 (SGLT2) inhibitor, which is to be administered as remogliflozin etabonate (Remo™, Remozen™), the prodrug for remogliflozin, recently received its first approval as a treatment for type 2 diabetes mellitus (T2DM) in India. This article summarizes the milestones in the development of remogliflozin etabonate leading to this first approval for T2DM.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Approval; Glucosides; Humans; Hypoglycemic Agents; India; Pyrazoles; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

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 (t

Topics: Blood Glucose; Bridged Bicyclo Compounds, Heterocyclic; Diabetes Mellitus, Type 2; Glucosides; Half-Life; Humans; Hypoglycemic Agents; Pyrazoles; Sodium-Glucose Transporter 2

Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) represent a new class of anti-hyperglycemic agents with a unique mechanism of action. These drugs lower blood glucose by increasing urinary glucose excretion. Remogliflozin etabonate (RE) is a prodrug of remogliflozin, an SGLT2 inhibitor under development.. The following article reviews all of the clinical studies published regarding metabolism, drug interaction, safety and efficacy of RE in healthy subjects, patients with type 1 and type 2 diabetes.. Available data suggest low potential for RE to interact with other drugs affecting the P450 system. Compared with placebo, RE reduces hemoglobin A1c (HbA1c) levels by an average of 0.5 - 1.0% after 12 weeks of therapy in drug-naive patients with type 2 diabetes. Because of its relatively short half-life, RE may be slightly more effective when used twice daily than once daily. One preliminary study also showed that RE decreased plasma glucose levels in type 1 diabetes. Advantages of RE include modest weight loss of ∼ 2 kg, low risk of hypoglycemia, and a trend toward decrease in blood pressure. The commonest adverse effects of RE are genital mycotic infections, urinary tract infections, and dizziness. However, further studies are needed to establish its long-term safety and efficacy, and to determine whether it has specific advantages over currently approved SGLT2 inhibitors.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Interactions; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Prodrugs; Pyrazoles; Sodium-Glucose Transporter 2 Inhibitors

The present review summarizes the existing literature data regarding the development of newer categories of antidiabetic agents, their mechanism of action and their clinical importance. In this paper, a review of the recent patents for the treatment of diabetes will be presented. In recent years significant achievements have been done, including the development of SGLT2 inhibitors, glucokinase activators as well as the role of free fatty acids and bile acid metabolism in the treatment of diabetes are reviewed.

Topics: Animals; Benzhydryl Compounds; Bile Acids and Salts; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Glucokinase; Glucosides; Humans; Hypoglycemic Agents; Molecular Targeted Therapy; Patents as Topic; Pyrazoles; Sodium-Glucose Transporter 2 Inhibitors

Topics: Animals; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Evaluation, Preclinical; Glucose; Glucosides; Humans; Hypoglycemic Agents; Kidney; Sodium-Glucose Transporter 2 Inhibitors

Remogliflozin Etabonate (RE) & Vildagliptin are twice-daily medications that are individually approved and widely used in India for the treatment of diabetes. A single pill fixed dose combination of RE & Vildagliptin was formulated as potential pharmaco-therapeutic agent that would not only offer beneficial pharmacologic effects, but also reduces the pill burden, leading to a simplified treatment regimen with better treatment compliance. The fixed dose combination (FDC) of Remogliflozin + Vildagliptin added on to Metformin has been evaluated in this pivotal phase III study.. This 16 week, multi-centric, prospective, double blind, double dummy, parallel group, randomized controlled study compared efficacy and safety of FDC of RE 100mg + Vildagliptin 50mg (RV) given twice daily with active comparator of Empagliflozin 25mg +Linagliptin 5mg (EL) given once daily. Adult T2DM patients with HbA1c 8-11% on Metformin stable dose of ≥1500mg for ≥8 weeks before screening were randomized to either of treatment arms. The study endpoints were mean changes from baseline (CFB) in HbA1c (primary), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), body weight (BW) and blood pressure (BP) for efficacy and adverse events (AE) monitoring for safety assessments.. Of 400 eligible subjects (200 in each arm), 357 (89.3%) subjects completed the study. The baseline demographic characteristics were well balanced between 2 treatment arms. In the mITT population, the least squares (LS) mean (SE) change from baseline in HbA1c levels at week 16 was -1.46% (0.098) in the RV arm and -1.38% (0.100) in the EL arm (p < 0.001 for within group change from baseline). The mean difference of -0.08% (95%CI: -0.28, 0.13) in HbA1c demonstrated non-inferiority (NI) of RV compared to EL (p<0.001 for NI test). Similarly, significant reduction was observed in FPG, PPG, BW and BP which was found to be comparable between the two treatment arms. Drug related AEs were observed in 5.5% and 4.5% subjects of EL and RV arm respectively, with low incidence of hypoglycemia, genital and urinary tract infections (0.5-3%).. Overall, FDC of Remogliflozin Etabonate + Vildagliptin added on to Metformin was found to be efficacious and well tolerated in the treatment of patients with T2DM, and demonstrated non-inferiority to Empagliflozin 25mg + Linagliptin 5mg treatment added on to Metformin.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Linagliptin; Metformin; Prospective Studies; Pyrazoles; Treatment Outcome; Vildagliptin

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.. 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.. 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.. 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.. ClinicalTrials.gov , NCT00519480 . Registered:22 August 2007.

Topics: Adult; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Fasting; Female; Glucosides; Humans; Hypoglycemic Agents; Insulin; Lactic Acid; Male; Metformin; Middle Aged; Pyrazoles

Metformin is the first-line treatment for type 2 diabetes mellitus (T2DM), but many patients either cannot tolerate it or cannot achieve glycemic control with metformin alone, so treatment with other glucose-lowering agents in combination with metformin is frequently required. Remogliflozin etabonate, a novel agent, is an orally bioavailable prodrug of remogliflozin, which is a potent and selective sodium-glucose co-transporter-2 inhibitor.. Our objective was to evaluate the efficacy and safety of remogliflozin etabonate compared with dapagliflozin in subjects with T2DM in whom a stable dose of metformin as monotherapy was providing inadequate glycemic control.. A 24-week randomized, double-blind, double-dummy, active-controlled, three-arm, parallel-group, multicenter, phase III study was conducted in India. Patients aged ≥ 18 and ≤ 65 years diagnosed with T2DM, receiving metformin ≥ 1500 mg/day, and with glycated hemoglobin (HbA1c) levels ≥ 7 to ≤ 10% at screening were randomized into three groups. Every patient received metformin ≥ 1500 mg and either remogliflozin etabonate 100 mg twice daily (BID) (group 1, n = 225) or remogliflozin etabonate 250 mg BID (group 2, n = 241) or dapagliflozin 10 mg once daily (QD) in the morning and placebo QD in the evening (group 3, n = 146). The patients were followed-up at weeks 1 and 4 and at 4-week intervals thereafter until week 24. The endpoints included mean change in HbA1c (primary endpoint, noninferiority margin = 0.35), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), bodyweight, blood pressure, and fasting lipids. Treatment-emergent adverse events (TEAEs), safety laboratory values, electrocardiogram, and vital signs were evaluated.. Of 612 randomized patients, 167 (group 1), 175 (group 2), and 103 (group 3) patients with comparable baseline characteristics completed the study. Mean change ± standard error (SE) in HbA1c from baseline to week 24 was - 0.72 ± 0.09, - 0.77 ± 0.09, and - 0.58 ± 0.12% in groups 1, 2, and 3, respectively. The difference in mean HbA1c of group 1 versus group 3 (- 0.14%, 90% confidence interval [CI] - 0.38 to 0.10) and group 2 versus group 3 (- 0.19%; 90% CI - 0.42 to 0.05) was noninferior to that in group 3 (p < 0.001). No significant difference was found between group 1 or group 2 and group 3 in change in FPG, PPG, and bodyweight. The overall incidence of TEAEs was comparable across study groups (group 1 = 32.6%, group 2 = 34.4%, group 3 = 29.5%), including adverse events (AEs) of special interest (hypoglycemic events, urinary tract infection, genital fungal infection). Most TEAEs were mild to moderate in intensity, and no severe AEs were reported.. This study demonstrated the noninferiority of remogliflozin etabonate 100 and 250 mg compared with dapagliflozin, from the first analysis of an initial 612 patients. Remogliflozin etabonate therefore may be considered an effective and well-tolerated alternative treatment option for glycemic control in T2DM.. CTRI/2017/07/009121.

Topics: Adolescent; Adult; Aged; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucosides; Humans; Hypoglycemic Agents; Male; Middle Aged; Prodrugs; Pyrazoles; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Time Factors; Young Adult

We compared the efficacy of twice-daily doses of remogliflozin etabonate (RE) and once-daily pioglitazone with placebo for reduction in glycated haemoglobin (HbA1c) concentration. In this 12-week, double-blind, randomized, active- and placebo-controlled trial, 336 treatment-naïve subjects with type 2 diabetes and an HbA1c of 7.0-9.5% (53-80 mmol/mol) were randomized to RE (50, 100, 250, 500 or 1000 mg twice daily), matching placebo or 30 mg pioglitazone once daily. The primary endpoint was change in HbA1c from baseline. Other endpoints included changes in body weight, lipid levels, safety and tolerability. RE produced a decreasing dose response in HbA1c at week 12 (p < 0.001), with reductions in HbA1c versus placebo ranging from 0.64 to 1.07% (p < 0.001). Statistically significant reductions in body weight for RE compared with placebo were also observed. Twice-daily RE resulted in a dose-ordered improvement in glycaemic control and was generally well tolerated.

Topics: Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Follow-Up Studies; Glucosides; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertriglyceridemia; Hypoglycemia; Hypoglycemic Agents; Intention to Treat Analysis; Membrane Transport Modulators; Middle Aged; Patient Dropouts; Pioglitazone; Prodrugs; Pyrazoles; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones; Weight Loss

The sodium-dependent glucose transporter 2 (SGLT2) inhibitor remogliflozin etabonate (RE) was evaluated in a 12-week, double-blind, randomized, placebo- and active-controlled, parallel-group study. A total of 252 newly diagnosed and drug-naïve people with type 2 diabetes and glycated haemoglobin (HbA1c) concentrations of 7.0-≤9.5% (53-80 mmol/mol) were recruited. Participants were randomized to RE (100, 250, 500 or 1000 mg once daily or 250 mg twice daily), placebo or 30 mg pioglitazone once daily. The primary endpoint was change in HbA1c concentration from baseline. Secondary endpoints included changes in fasting plasma glucose, body weight and lipid profiles, safety and tolerability. We observed a statistically significant trend in the RE dose-response relationship for change from baseline in HbA1c at week 12 (p < 0.047). RE was generally well tolerated and no effects on LDL cholesterol were observed.

Topics: Cohort Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Follow-Up Studies; Glucosides; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Intention to Treat Analysis; Membrane Transport Modulators; Middle Aged; Patient Dropouts; Pioglitazone; Prodrugs; Pyrazoles; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones; Weight Loss

The sodium-dependent glucose co-transporter-2 (SGLT2) is expressed in absorptive epithelia of the renal tubules. Remogliflozin etabonate (RE) is the prodrug of remogliflozin, the active entity that inhibits SGLT2. An inhibitor of this pathway would enhance urinary glucose excretion (UGE), and potentially improve plasma glucose concentrations in diabetic patients. RE is intended for use for the treatment of type 2 diabetes mellitus (T2DM) as monotherapy and in combination with existing therapies. Metformin, a dimethylbiguanide, is an effective oral antihyperglycemic agent widely used for the treatment of T2DM.. This was a randomized, open-label, repeat-dose, two-sequence, cross-over study in 13 subjects with T2DM. Subjects were randomized to one of two treatment sequences in which they received either metformin alone, RE alone, or both over three, 3-day treatment periods separated by two non-treatment intervals of variable duration. On the evening before each treatment period, subjects were admitted and confined to the clinical site for the duration of the 3-day treatment period. Pharmacokinetic, pharmacodynamic (urine glucose and fasting plasma glucose), and safety (adverse events, vital signs, ECG, clinical laboratory parameters including lactic acid) assessments were performed at check-in and throughout the treatment periods. Pharmacokinetic sampling occurred on Day 3 of each treatment period.. This study demonstrated the lack of effect of RE on steady state metformin pharmacokinetics. Metformin did not affect the AUC of RE, remogliflozin, or its active metabolite, GSK279782, although Cmax values were slightly lower for remogliflozin and its metabolite after co-administration with metformin compared with administration of RE alone. Metformin did not alter the pharmacodynamic effects (UGE) of RE. Concomitant administration of metformin and RE was well tolerated with minimal hypoglycemia, no serious adverse events, and no increase in lactic acid.. Coadministration of metformin and RE was well tolerated in this study. The results support continued development of RE as a treatment for T2DM.. ClinicalTrials.gov, NCT00376038.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Glucosides; Glycosuria; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Prodrugs; Pyrazoles; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

Remogliflozin etabonate (RE) is the prodrug of remogliflozin, a selective inhibitor of the renal sodium-dependent glucose transporter 2 (SGLT2), which could increase urine glucose excretion (UGE) and lower plasma glucose in humans.. This double-blind, randomized, placebo-controlled, single-dose, dose-escalation, crossover study is the first human trial designed to evaluate safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of RE. All subjects received single oral doses of either RE or placebo separated by approximately 2 week intervals. In Part A, 10 healthy subjects participated in 5 dosing periods where they received RE (20 mg, 50 mg, 150 mg, 500 mg, or 1000 mg) or placebo (4:1 active to placebo ratio per treatment period). In Part B, 6 subjects with type 2 diabetes mellitus (T2DM) participated in 3 dose periods where they received RE (50 mg and 500 mg) or placebo (2:1 active to placebo per treatment period). The study protocol was registered with the NIH clinical trials data base with identifier NCT01571661.. RE was generally well-tolerated; there were no serious adverse events. In both populations, RE was rapidly absorbed and converted to remogliflozin (time to maximum plasma concentration [Cmax;Tmax] approximately 1 h). Generally, exposure to remogliflozin was proportional to the administered dose. RE was rapidly eliminated (mean T½ of ~25 min; mean plasma T½ for remogliflozin was 120 min) and was independent of dose. All subjects showed dose-dependent increases in 24-hour UGE, which plateaued at approximately 200 to 250 mmol glucose with RE doses ≥150 mg. In T2DM subjects, increased plasma glucose following OGTT was attenuated by RE in a drug-dependent fashion, but there were no clear trends in plasma insulin. There were no apparent effects of treatment on plasma or urine electrolytes.. The results support progression of RE as a potential treatment for T2DM.. ClinicalTrials.gov NCT01571661.

Topics: Adult; Area Under Curve; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Diarrhea; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Electrolytes; Female; Glucosides; Headache; Humans; Hypoglycemic Agents; Insulin; Male; Metabolic Clearance Rate; Middle Aged; Molecular Structure; Pyrazoles; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

Remogliflozin etabonate (RE) is the pro-drug of remogliflozin (R), a selective inhibitor of renal sodium-dependent glucose transporter 2 (SGLT2) that improves glucose control via enhanced urinary glucose excretion (UGE). This study evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of RE in subjects with type 2 diabetes mellitus (T2DM).. In a double-blinded, randomized, placebo-controlled trial, subjects who were drug-naïve or had metformin discontinued received RE [100 mg BID (n = 9), 1000 mg QD (n = 9), 1000 mg BID (n = 9)], or placebo (n = 8) for 12 days. Safety parameters were assessed, including urine studies to evaluate renal function. Plasma concentrations of RE and metabolites were measured with the first dose and at steady state. RE effects on glucose levels were assessed with fasting glucose concentrations, frequently sampled 24-h glucose profiles and oral glucose tolerance tests.. No significant laboratory abnormalities or safety events were reported; the most frequent adverse events were headache and flatulence. Plasma exposure to RE and R were proportional to administered dose with negligible accumulation. Mean 24-h UGE increased in RE treatment groups. Compared with the placebo group, 24-h mean (95% CI) changes in plasma glucose were -1.2 (-2.2 to -0.3) (100 mg BID), -0.8 (-1.7 to 0.2) (1000 mg QD) and -1.7 (-2.7 to -0.8) mmol/l (1000 mg BID).. Administration of RE for 12 days is well-tolerated and results in clinically meaningful improvements in plasma glucose, accompanied by changes in body weight and blood pressure in subjects with T2DM.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucose Tolerance Test; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Pyrazoles; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

Inhibition of the sodium-glucose co-transporters (SGLT1 and SGLT2) is a validated strategy to address the increasing prevalence of type II diabetes mellitus. However, achieving selective inhibition of human SGLT1 or SGLT2 remains challenging. Orally available small molecule drugs based on the d-glucose core of the natural product Gliflozin have proven to be clinically effective in this regard, effectively impeding glucose reabsorption. Herein, we disclose the influence of molecular editing with fluorine at the C2 position of the pyranose ring of Phlorizin analogues Remogliflozin Etabonate and Dapagliflozin (Farxiga

Topics: Administration, Oral; Benzhydryl Compounds; Blood Glucose; Diabetes Mellitus, Type 2; Fluorine; Glucosides; Glycosylation; Humans; Hypoglycemic Agents; Pyrazoles; Sodium-Glucose Transporter 2 Inhibitors