PMID- 32162274 OWN - NLM STAT- MEDLINE DCOM- 20201229 LR - 20201229 IS - 1179-1950 (Electronic) IS - 0012-6667 (Print) IS - 0012-6667 (Linking) VI - 80 IP - 6 DP - 2020 Apr TI - 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. PG - 587-600 LID - 10.1007/s40265-020-01285-0 [doi] AB - 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 /= 1500 mg/day, and with glycated hemoglobin (HbA1c) levels >/= 7 to /= 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. FAU - Dharmalingam, Mala AU - Dharmalingam M AD - MS Ramaiah Memorial Hospital, Bangalore, India. FAU - Aravind, S R AU - Aravind SR AD - Diacon Hospital, Bangalore, India. FAU - Thacker, Hemant AU - Thacker H AD - Bhatia Hospital, Mumbai, India. FAU - Paramesh, S AU - Paramesh S AD - Bangalore Diabetes and Diagnostic Centre, Bangalore, India. FAU - Mohan, Brij AU - Mohan B AD - BMC Hospital and Diabetes Centre, Kanpur, India. FAU - Chawla, Manoj AU - Chawla M AD - Lina Diabetes Centre, Mumbai, India. FAU - Asirvatham, Arthur AU - Asirvatham A AD - Arthur Asirvatham Hospital, Madurai, India. FAU - Goyal, Ramesh AU - Goyal R AD - Apollo Hospital, Ahmedabad, India. FAU - Shembalkar, Jayashri AU - Shembalkar J AD - Getwell Hospital and Research Institute, Nagpur, India. FAU - Balamurugan, R AU - Balamurugan R AD - Kovai Diabetes Speciality Centre and Hospital, Coimbatore, India. FAU - Kadam, Pradnya AU - Kadam P AD - Inamdar Multispecialty Hospital, Pune, India. FAU - Alva, Hansraj AU - Alva H AD - Vinaya Hospital and Research Centre, Mangalore, India. FAU - Kodgule, Rahul AU - Kodgule R AD - Medical Services, Glenmark Pharmaceuticals Ltd, Andheri East, Mumbai, Maharashtra, 400 099, India. FAU - Tandon, Monika AU - Tandon M AD - Medical Services, Glenmark Pharmaceuticals Ltd, Andheri East, Mumbai, Maharashtra, 400 099, India. FAU - Vaidyanathan, Sivakumar AU - Vaidyanathan S AD - Medical Services, Glenmark Pharmaceuticals Ltd, Andheri East, Mumbai, Maharashtra, 400 099, India. FAU - Pendse, Amol AU - Pendse A AD - Medical Services, Glenmark Pharmaceuticals Ltd, Andheri East, Mumbai, Maharashtra, 400 099, India. FAU - Gaikwad, Rajesh AU - Gaikwad R AD - Medical Services, Glenmark Pharmaceuticals Ltd, Andheri East, Mumbai, Maharashtra, 400 099, India. FAU - Katare, Sagar AU - Katare S AD - Medical Services, Glenmark Pharmaceuticals Ltd, Andheri East, Mumbai, Maharashtra, 400 099, India. sagar.katare@glenmarkpharma.com. FAU - Suryawanshi, Sachin AU - Suryawanshi S AD - Medical Services, Glenmark Pharmaceuticals Ltd, Andheri East, Mumbai, Maharashtra, 400 099, India. FAU - Barkate, Hanmant AU - Barkate H AD - Medical Services, Glenmark Pharmaceuticals Ltd, Andheri East, Mumbai, Maharashtra, 400 099, India. LA - eng SI - CTRI/CTRI/2017/07/009121 PT - Clinical Trial, Phase III PT - Controlled Clinical Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0 (Prodrugs) RN - 0 (Pyrazoles) RN - 0 (Sodium-Glucose Transporter 2) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - TR0QT6QSUL (remogliflozin etabonate) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism MH - Double-Blind Method MH - Female MH - Glucosides/administration & dosage/*adverse effects/*therapeutic use MH - Humans MH - Hypoglycemic Agents/administration & dosage/*adverse effects/*therapeutic use MH - Male MH - Middle Aged MH - Prodrugs/administration & dosage/pharmacology/therapeutic use MH - Pyrazoles/administration & dosage/*adverse effects/*therapeutic use MH - Sodium-Glucose Transporter 2/*metabolism MH - Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/*adverse effects/*therapeutic use MH - Time Factors MH - Young Adult PMC - PMC7165159 COIS- Rahul Kodgule, Monika Tandon, Sivakumar Vaidyanathan, Amol Pendse, Rajesh Gaikwad, Sagar Katare, Sachin Suryawanshi, and Hanmant Barkate are employees of Glenmark Pharmaceuticals Limited. Mala Dharmalingam, S.R Aravind, Hemant Thacker, S. Paramesh, Brij Mohan, Manoj Chawla, Arthur Asirvatham, Ramesh Goyal, Jayashri Shembalkar, R. Balamurugan, Pradnya Kadam, and Hansraj Alva have no conflicts of interest that are directly relevant to the content of this article. EDAT- 2020/03/13 06:00 MHDA- 2020/12/30 06:00 PMCR- 2020/03/11 CRDT- 2020/03/13 06:00 PHST- 2020/03/13 06:00 [pubmed] PHST- 2020/12/30 06:00 [medline] PHST- 2020/03/13 06:00 [entrez] PHST- 2020/03/11 00:00 [pmc-release] AID - 10.1007/s40265-020-01285-0 [pii] AID - 1285 [pii] AID - 10.1007/s40265-020-01285-0 [doi] PST - ppublish SO - Drugs. 2020 Apr;80(6):587-600. doi: 10.1007/s40265-020-01285-0.