Efficacy and Safety of Remogliflozin Etabonate, a New Sodium Glucose Co-Transporter-2 Inhibitor, in Patients with Type 2 Diabetes Mellitus: A 24-Week, Randomized, Double-Blind, Active-Controlled Trial
Background 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. Remoglifloz...
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| Veröffentlicht in: | Drugs (New York, N.Y.) N.Y.), 2020-04, Vol.80 (6), p.587-600 |
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| creator | Dharmalingam, Mala Aravind, S. R. Thacker, Hemant Paramesh, S. Mohan, Brij Chawla, Manoj Asirvatham, Arthur Goyal, Ramesh Shembalkar, Jayashri Balamurugan, R. Kadam, Pradnya Alva, Hansraj Kodgule, Rahul Tandon, Monika Vaidyanathan, Sivakumar Pendse, Amol Gaikwad, Rajesh Katare, Sagar Suryawanshi, Sachin Barkate, Hanmant |
| description | Background
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.
Objective
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.
Methods
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.
Results
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
|
| doi_str_mv | 10.1007/s40265-020-01285-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7165159</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2394349149</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-4fa5f1d8b89ab8a5549b9d1029e5b23d3507b603fa06f34b95115463fe851aac3</originalsourceid><addsrcrecordid>eNp9UU1vEzEQXSEQDYU_wAFZ4hqD7bV3Yw5IaRpKpfKhNoij5d0dJy7OOtjeVukv7M-qQ0qBC6eZ8bz35lmvKF5S8oYSUr-NnLBKYMIIJpRNcveoGFFaS0ylII-LEcnPuKqq-qB4FuPlbpRCPi0OSkYrxmo-Km7nxthWt1uk-w5daANpi7xB57D2S2eN8ze2R_OkG9_rBGOk0We4Rhe-s8Manbih9RHQzONF0H3c-JAgYIZO-5VtbPJhjDL9q04W-hTRtU0rtNhuADF0bHUDCSL6BM7ZNMR3aIoYx98BfozRebbj1_YGujE69kPjAB852-dp2iZ7BXjm-xS8c9ChRbDaPS-eGO0ivLivh8W3D_PF7CM--3JyOpue4ZbXPGFutDC0mzQTqZuJFoLLRnaUMAmiYWVXClI3FSmNJpUpeSMFpYJXpYGJoFq35WHxfq-7GZo1dG3-V9BObYJd67BVXlv176a3K7X0V6qmlaBCZoHX9wLB_xwgJnXph9Bnz4qVkpdcUr5DsT2qDT7GAObhAiVql77ap69y-upX-opk0qu_vT1QfsedAeUeEPOqX0L4c_s_snf0k7xy</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2394349149</pqid></control><display><type>article</type><title>Efficacy and Safety of Remogliflozin Etabonate, a New Sodium Glucose Co-Transporter-2 Inhibitor, in Patients with Type 2 Diabetes Mellitus: A 24-Week, Randomized, Double-Blind, Active-Controlled Trial</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Dharmalingam, Mala ; Aravind, S. R. ; Thacker, Hemant ; Paramesh, S. ; Mohan, Brij ; Chawla, Manoj ; Asirvatham, Arthur ; Goyal, Ramesh ; Shembalkar, Jayashri ; Balamurugan, R. ; Kadam, Pradnya ; Alva, Hansraj ; Kodgule, Rahul ; Tandon, Monika ; Vaidyanathan, Sivakumar ; Pendse, Amol ; Gaikwad, Rajesh ; Katare, Sagar ; Suryawanshi, Sachin ; Barkate, Hanmant</creator><creatorcontrib>Dharmalingam, Mala ; Aravind, S. R. ; Thacker, Hemant ; Paramesh, S. ; Mohan, Brij ; Chawla, Manoj ; Asirvatham, Arthur ; Goyal, Ramesh ; Shembalkar, Jayashri ; Balamurugan, R. ; Kadam, Pradnya ; Alva, Hansraj ; Kodgule, Rahul ; Tandon, Monika ; Vaidyanathan, Sivakumar ; Pendse, Amol ; Gaikwad, Rajesh ; Katare, Sagar ; Suryawanshi, Sachin ; Barkate, Hanmant</creatorcontrib><description>Background
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.
Objective
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.
Methods
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.
Results
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.
Conclusion
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.
Trial Registration
CTRI/2017/07/009121.</description><identifier>ISSN: 0012-6667</identifier><identifier>EISSN: 1179-1950</identifier><identifier>DOI: 10.1007/s40265-020-01285-0</identifier><identifier>PMID: 32162274</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject><![CDATA[Active control ; Adolescent ; Adult ; Aged ; Bioavailability ; Blood pressure ; Cholesterol ; Clinical medicine ; Confidence intervals ; Control methods ; CTRI ; CTRI/2017/07/009121 ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - metabolism ; Double-Blind Method ; Double-blind studies ; Drug dosages ; EKG ; Electrocardiography ; Error analysis ; Fasting ; Female ; Glucose ; Glucose transporter ; Glucosides - administration & dosage ; Glucosides - adverse effects ; Glucosides - therapeutic use ; Hemoglobin ; Humans ; Hypoglycemic Agents - administration & dosage ; Hypoglycemic Agents - adverse effects ; Hypoglycemic Agents - therapeutic use ; Infections ; Inhibitors ; Internal Medicine ; Laboratories ; Laboratory testing ; Lipids ; Male ; Medicine ; Medicine & Public Health ; Metformin ; Middle Aged ; Original ; Original Research Article ; Patients ; Pharmacology/Toxicology ; Pharmacotherapy ; Plasma ; Prodrugs - administration & dosage ; Prodrugs - pharmacology ; Prodrugs - therapeutic use ; Pyrazoles - administration & dosage ; Pyrazoles - adverse effects ; Pyrazoles - therapeutic use ; Randomization ; Safety ; Sodium ; Sodium-Glucose Transporter 2 - metabolism ; Sodium-Glucose Transporter 2 Inhibitors - administration & dosage ; Sodium-Glucose Transporter 2 Inhibitors - adverse effects ; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use ; Standard error ; Time Factors ; Urinary tract ; Vital signs ; Young Adult]]></subject><ispartof>Drugs (New York, N.Y.), 2020-04, Vol.80 (6), p.587-600</ispartof><rights>The Author(s) 2020</rights><rights>Copyright Springer Nature B.V. Apr 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-4fa5f1d8b89ab8a5549b9d1029e5b23d3507b603fa06f34b95115463fe851aac3</citedby><cites>FETCH-LOGICAL-c474t-4fa5f1d8b89ab8a5549b9d1029e5b23d3507b603fa06f34b95115463fe851aac3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s40265-020-01285-0$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s40265-020-01285-0$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32162274$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dharmalingam, Mala</creatorcontrib><creatorcontrib>Aravind, S. R.</creatorcontrib><creatorcontrib>Thacker, Hemant</creatorcontrib><creatorcontrib>Paramesh, S.</creatorcontrib><creatorcontrib>Mohan, Brij</creatorcontrib><creatorcontrib>Chawla, Manoj</creatorcontrib><creatorcontrib>Asirvatham, Arthur</creatorcontrib><creatorcontrib>Goyal, Ramesh</creatorcontrib><creatorcontrib>Shembalkar, Jayashri</creatorcontrib><creatorcontrib>Balamurugan, R.</creatorcontrib><creatorcontrib>Kadam, Pradnya</creatorcontrib><creatorcontrib>Alva, Hansraj</creatorcontrib><creatorcontrib>Kodgule, Rahul</creatorcontrib><creatorcontrib>Tandon, Monika</creatorcontrib><creatorcontrib>Vaidyanathan, Sivakumar</creatorcontrib><creatorcontrib>Pendse, Amol</creatorcontrib><creatorcontrib>Gaikwad, Rajesh</creatorcontrib><creatorcontrib>Katare, Sagar</creatorcontrib><creatorcontrib>Suryawanshi, Sachin</creatorcontrib><creatorcontrib>Barkate, Hanmant</creatorcontrib><title>Efficacy and Safety of Remogliflozin Etabonate, a New Sodium Glucose Co-Transporter-2 Inhibitor, in Patients with Type 2 Diabetes Mellitus: A 24-Week, Randomized, Double-Blind, Active-Controlled Trial</title><title>Drugs (New York, N.Y.)</title><addtitle>Drugs</addtitle><addtitle>Drugs</addtitle><description>Background
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.
Objective
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.
Methods
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.
Results
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.
Conclusion
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.
Trial Registration
CTRI/2017/07/009121.</description><subject>Active control</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Bioavailability</subject><subject>Blood pressure</subject><subject>Cholesterol</subject><subject>Clinical medicine</subject><subject>Confidence intervals</subject><subject>Control methods</subject><subject>CTRI</subject><subject>CTRI/2017/07/009121</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Double-Blind Method</subject><subject>Double-blind studies</subject><subject>Drug dosages</subject><subject>EKG</subject><subject>Electrocardiography</subject><subject>Error analysis</subject><subject>Fasting</subject><subject>Female</subject><subject>Glucose</subject><subject>Glucose transporter</subject><subject>Glucosides - administration & dosage</subject><subject>Glucosides - adverse effects</subject><subject>Glucosides - therapeutic use</subject><subject>Hemoglobin</subject><subject>Humans</subject><subject>Hypoglycemic Agents - administration & dosage</subject><subject>Hypoglycemic Agents - adverse effects</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Infections</subject><subject>Inhibitors</subject><subject>Internal Medicine</subject><subject>Laboratories</subject><subject>Laboratory testing</subject><subject>Lipids</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metformin</subject><subject>Middle Aged</subject><subject>Original</subject><subject>Original Research Article</subject><subject>Patients</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacotherapy</subject><subject>Plasma</subject><subject>Prodrugs - administration & dosage</subject><subject>Prodrugs - pharmacology</subject><subject>Prodrugs - therapeutic use</subject><subject>Pyrazoles - administration & dosage</subject><subject>Pyrazoles - adverse effects</subject><subject>Pyrazoles - therapeutic use</subject><subject>Randomization</subject><subject>Safety</subject><subject>Sodium</subject><subject>Sodium-Glucose Transporter 2 - metabolism</subject><subject>Sodium-Glucose Transporter 2 Inhibitors - administration & dosage</subject><subject>Sodium-Glucose Transporter 2 Inhibitors - adverse effects</subject><subject>Sodium-Glucose Transporter 2 Inhibitors - therapeutic use</subject><subject>Standard error</subject><subject>Time Factors</subject><subject>Urinary tract</subject><subject>Vital signs</subject><subject>Young Adult</subject><issn>0012-6667</issn><issn>1179-1950</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9UU1vEzEQXSEQDYU_wAFZ4hqD7bV3Yw5IaRpKpfKhNoij5d0dJy7OOtjeVukv7M-qQ0qBC6eZ8bz35lmvKF5S8oYSUr-NnLBKYMIIJpRNcveoGFFaS0ylII-LEcnPuKqq-qB4FuPlbpRCPi0OSkYrxmo-Km7nxthWt1uk-w5daANpi7xB57D2S2eN8ze2R_OkG9_rBGOk0We4Rhe-s8Manbih9RHQzONF0H3c-JAgYIZO-5VtbPJhjDL9q04W-hTRtU0rtNhuADF0bHUDCSL6BM7ZNMR3aIoYx98BfozRebbj1_YGujE69kPjAB852-dp2iZ7BXjm-xS8c9ChRbDaPS-eGO0ivLivh8W3D_PF7CM--3JyOpue4ZbXPGFutDC0mzQTqZuJFoLLRnaUMAmiYWVXClI3FSmNJpUpeSMFpYJXpYGJoFq35WHxfq-7GZo1dG3-V9BObYJd67BVXlv176a3K7X0V6qmlaBCZoHX9wLB_xwgJnXph9Bnz4qVkpdcUr5DsT2qDT7GAObhAiVql77ap69y-upX-opk0qu_vT1QfsedAeUeEPOqX0L4c_s_snf0k7xy</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Dharmalingam, Mala</creator><creator>Aravind, S. R.</creator><creator>Thacker, Hemant</creator><creator>Paramesh, S.</creator><creator>Mohan, Brij</creator><creator>Chawla, Manoj</creator><creator>Asirvatham, Arthur</creator><creator>Goyal, Ramesh</creator><creator>Shembalkar, Jayashri</creator><creator>Balamurugan, R.</creator><creator>Kadam, Pradnya</creator><creator>Alva, Hansraj</creator><creator>Kodgule, Rahul</creator><creator>Tandon, Monika</creator><creator>Vaidyanathan, Sivakumar</creator><creator>Pendse, Amol</creator><creator>Gaikwad, Rajesh</creator><creator>Katare, Sagar</creator><creator>Suryawanshi, Sachin</creator><creator>Barkate, Hanmant</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>4T-</scope><scope>7QO</scope><scope>7RV</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20200401</creationdate><title>Efficacy and Safety of Remogliflozin Etabonate, a New Sodium Glucose Co-Transporter-2 Inhibitor, in Patients with Type 2 Diabetes Mellitus: A 24-Week, Randomized, Double-Blind, Active-Controlled Trial</title><author>Dharmalingam, Mala ; Aravind, S. R. ; Thacker, Hemant ; Paramesh, S. ; Mohan, Brij ; Chawla, Manoj ; Asirvatham, Arthur ; Goyal, Ramesh ; Shembalkar, Jayashri ; Balamurugan, R. ; Kadam, Pradnya ; Alva, Hansraj ; Kodgule, Rahul ; Tandon, Monika ; Vaidyanathan, Sivakumar ; Pendse, Amol ; Gaikwad, Rajesh ; Katare, Sagar ; Suryawanshi, Sachin ; Barkate, Hanmant</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-4fa5f1d8b89ab8a5549b9d1029e5b23d3507b603fa06f34b95115463fe851aac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Active control</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Bioavailability</topic><topic>Blood pressure</topic><topic>Cholesterol</topic><topic>Clinical medicine</topic><topic>Confidence intervals</topic><topic>Control methods</topic><topic>CTRI</topic><topic>CTRI/2017/07/009121</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Double-Blind Method</topic><topic>Double-blind studies</topic><topic>Drug dosages</topic><topic>EKG</topic><topic>Electrocardiography</topic><topic>Error analysis</topic><topic>Fasting</topic><topic>Female</topic><topic>Glucose</topic><topic>Glucose transporter</topic><topic>Glucosides - administration & dosage</topic><topic>Glucosides - adverse effects</topic><topic>Glucosides - therapeutic use</topic><topic>Hemoglobin</topic><topic>Humans</topic><topic>Hypoglycemic Agents - administration & dosage</topic><topic>Hypoglycemic Agents - adverse effects</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Infections</topic><topic>Inhibitors</topic><topic>Internal Medicine</topic><topic>Laboratories</topic><topic>Laboratory testing</topic><topic>Lipids</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metformin</topic><topic>Middle Aged</topic><topic>Original</topic><topic>Original Research Article</topic><topic>Patients</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacotherapy</topic><topic>Plasma</topic><topic>Prodrugs - administration & dosage</topic><topic>Prodrugs - pharmacology</topic><topic>Prodrugs - therapeutic use</topic><topic>Pyrazoles - administration & dosage</topic><topic>Pyrazoles - adverse effects</topic><topic>Pyrazoles - therapeutic use</topic><topic>Randomization</topic><topic>Safety</topic><topic>Sodium</topic><topic>Sodium-Glucose Transporter 2 - metabolism</topic><topic>Sodium-Glucose Transporter 2 Inhibitors - administration & dosage</topic><topic>Sodium-Glucose Transporter 2 Inhibitors - adverse effects</topic><topic>Sodium-Glucose Transporter 2 Inhibitors - therapeutic use</topic><topic>Standard error</topic><topic>Time Factors</topic><topic>Urinary tract</topic><topic>Vital signs</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dharmalingam, Mala</creatorcontrib><creatorcontrib>Aravind, S. R.</creatorcontrib><creatorcontrib>Thacker, Hemant</creatorcontrib><creatorcontrib>Paramesh, S.</creatorcontrib><creatorcontrib>Mohan, Brij</creatorcontrib><creatorcontrib>Chawla, Manoj</creatorcontrib><creatorcontrib>Asirvatham, Arthur</creatorcontrib><creatorcontrib>Goyal, Ramesh</creatorcontrib><creatorcontrib>Shembalkar, Jayashri</creatorcontrib><creatorcontrib>Balamurugan, R.</creatorcontrib><creatorcontrib>Kadam, Pradnya</creatorcontrib><creatorcontrib>Alva, Hansraj</creatorcontrib><creatorcontrib>Kodgule, Rahul</creatorcontrib><creatorcontrib>Tandon, Monika</creatorcontrib><creatorcontrib>Vaidyanathan, Sivakumar</creatorcontrib><creatorcontrib>Pendse, Amol</creatorcontrib><creatorcontrib>Gaikwad, Rajesh</creatorcontrib><creatorcontrib>Katare, Sagar</creatorcontrib><creatorcontrib>Suryawanshi, Sachin</creatorcontrib><creatorcontrib>Barkate, Hanmant</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Docstoc</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>Proquest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Drugs (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dharmalingam, Mala</au><au>Aravind, S. R.</au><au>Thacker, Hemant</au><au>Paramesh, S.</au><au>Mohan, Brij</au><au>Chawla, Manoj</au><au>Asirvatham, Arthur</au><au>Goyal, Ramesh</au><au>Shembalkar, Jayashri</au><au>Balamurugan, R.</au><au>Kadam, Pradnya</au><au>Alva, Hansraj</au><au>Kodgule, Rahul</au><au>Tandon, Monika</au><au>Vaidyanathan, Sivakumar</au><au>Pendse, Amol</au><au>Gaikwad, Rajesh</au><au>Katare, Sagar</au><au>Suryawanshi, Sachin</au><au>Barkate, Hanmant</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and Safety of Remogliflozin Etabonate, a New Sodium Glucose Co-Transporter-2 Inhibitor, in Patients with Type 2 Diabetes Mellitus: A 24-Week, Randomized, Double-Blind, Active-Controlled Trial</atitle><jtitle>Drugs (New York, N.Y.)</jtitle><stitle>Drugs</stitle><addtitle>Drugs</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>80</volume><issue>6</issue><spage>587</spage><epage>600</epage><pages>587-600</pages><issn>0012-6667</issn><eissn>1179-1950</eissn><abstract>Background
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.
Objective
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.
Methods
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.
Results
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.
Conclusion
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.
Trial Registration
CTRI/2017/07/009121.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>32162274</pmid><doi>10.1007/s40265-020-01285-0</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-6667 |
| ispartof | Drugs (New York, N.Y.), 2020-04, Vol.80 (6), p.587-600 |
| issn | 0012-6667 1179-1950 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7165159 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Active control Adolescent Adult Aged Bioavailability Blood pressure Cholesterol Clinical medicine Confidence intervals Control methods CTRI CTRI/2017/07/009121 Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Double-Blind Method Double-blind studies Drug dosages EKG Electrocardiography Error analysis Fasting Female Glucose Glucose transporter Glucosides - administration & dosage Glucosides - adverse effects Glucosides - therapeutic use Hemoglobin Humans Hypoglycemic Agents - administration & dosage Hypoglycemic Agents - adverse effects Hypoglycemic Agents - therapeutic use Infections Inhibitors Internal Medicine Laboratories Laboratory testing Lipids Male Medicine Medicine & Public Health Metformin Middle Aged Original Original Research Article Patients Pharmacology/Toxicology Pharmacotherapy Plasma Prodrugs - administration & dosage Prodrugs - pharmacology Prodrugs - therapeutic use Pyrazoles - administration & dosage Pyrazoles - adverse effects Pyrazoles - therapeutic use Randomization Safety Sodium Sodium-Glucose Transporter 2 - metabolism Sodium-Glucose Transporter 2 Inhibitors - administration & dosage Sodium-Glucose Transporter 2 Inhibitors - adverse effects Sodium-Glucose Transporter 2 Inhibitors - therapeutic use Standard error Time Factors Urinary tract Vital signs Young Adult |
| title | Efficacy and Safety of Remogliflozin Etabonate, a New Sodium Glucose Co-Transporter-2 Inhibitor, in Patients with Type 2 Diabetes Mellitus: A 24-Week, Randomized, Double-Blind, Active-Controlled Trial |
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