DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20212242

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

Soumya Sengupta, Sunita Sengupta, Sagar Katare

Abstract


Background: The aim of the study was to evaluate effectiveness and safety of remogliflozin etabonate in a real-world outpatient setting in type 2 diabetes mellitus (T2DM) patients in India.

Methods: A retrospective, observational, single-center study wherein medical records of adult patients (≥18 years old) with T2DM managed with remogliflozin 100 mg for at least three months at the diabetes care center in Jharkhand were retrieved. The effectiveness was assessed in terms of change from baseline in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), total body weight, blood pressure (BP, systolic and diastolic), kidney function tests, and lipid parameters after three months of treatment. Safety was assessed by adverse events (AEs) and serious AEs.

Results: Half of the patients received ≥3 concomitant antidiabetic drugs, common being sulphonylureas (92%), and metformin (91%). Remogliflozin treatment resulted in a significant mean reduction from baseline in HbA1c [-1.99 (0.12%); p<0.001], FPG [-52.3 (4.31) mg/dl; p<0.001] and PPG [-103.6 (7.10) mg/dl; p<0.001). Bodyweight reduction was not statistically significant [-0.1 (10.12) kg]. A significant reduction was observed in the systolic BP [-15.9 (2.21) mmHg; p<0.001] and diastolic BP [-3.3 (0.95) mmHg; p=0.001]. Commonly reported AE was heartburn (51.4%) and urinary tract infections (34.2%). No serious AEs were reported. The mean estimated glomerular filtration rate showed a statistically significant reduction of -1.55 (0.61) ml/min. The lipid parameter findings were non-significant.

Conclusions: The real-world experience of remogliflozin administered concomitantly with other antidiabetic drugs was effective and well-tolerated in Indian patients with T2DM.

 


Keywords


Glycated hemoglobin, Real-world, Remogliflozin etabonate, Sodium-glucose cotransporter-2 inhibitor, Type 2 diabetes mellitus

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References


Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843.

International Diabetes Federation. IDF Diabetes Atlas 9th edition; 2019. Available at: https://www.diabetesatlas.org/enresources. Accessed on 10 March 2021.

Dey L, Sttele AS, Yuan C. Alternative therapies for type 2 diabetes. Altern Med Rev. 2002;7:45-58.

Choi CI. Sodium-Glucose co-transporter 2 (SGLT2) inhibitors from natural products: discovery of next-generation antihyperglycemic agents. Molecules. 2016;21:1136.

International Diabetes Federation. Global guideline for type 2 diabetes, 2012. Available at: https://www.iapb.org/wpcontent/uploads/GlobalGuideline-for-Type-2-Diabetes-IDF-2012. Accessed on 10 March 2021.

National Institute for Health and Clinical Excellence. Type 2 diabetes: The Management of type 2 diabetes (NICE clinical guideline 87), 2009. Available at: https://www.nice.org.uk/guidance/ta203/documents/nicerecommendsfortype-2diabetesmellitus.Accessed on 10 March 2021.

Irons BK, Minze MG. Drug treatment of type 2 diabetes mellitus in patients for whom metformin is contraindicated. Diabetes Metab Syndr Obes. 2014;7:15-24.

Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35(6):1364-79.

Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. American Association of Clinical Endocrinologists' comprehensive diabetes management algorithm 2013 consensus statement. Endocr Pract. 2013;19:1-48.

Kalra S, Ghosh S, Aamir AH, Ahmed M, Amin MF, Bajaj S, et al. Safe and pragmatic use of sodium–glucose co-transporter 2 inhibitors in type 2 diabetes mellitus: South Asian Federation of Endocrine Societies consensus statement. Indian J Endocr Metab. 2017;21:210-30.

Abdul GMA, Norton L, Fronzo RA. Efficacy and safety of SGLT2 inhibitors in the treatment of type 2 diabetes. Curr Diabetes Rep. 2012;12:230-8.

Vallon V. The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus. Annu Rev Med. 2015;66:255-70.

Hsia DS, Grove O, Cefalu WT. An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus. Curr Opin Endocrinol Diabetes Obes. 2017;24:73-9.

Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, et al. Sodium-glucose co-transporter 2 inhibitors for type 2 diabetes: a systematic review and metaanalysis. Ann Intern Med. 2013;159:262-74.

Stenlof K, Cefalu WT, Kim KA, Alba M, Usiskin K, Tong C, et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab. 2013;15:372-82.

Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient Centered Approach. Diabetes Care. 2015;38:140-49.

Singh AK, Unnikrishnan AG, Zargar A, Kumar A, Das AK, Saboo B, et al. Evidence-Based Consensus on Positioning of SGLT2i in Type 2 Diabetes Mellitus in Indians. Diabetes Ther. 2019;10:393-428.

Dharmalingam M, Aravind SR, Thacker H, Paramesh S, Mohan B, Chawla M, et al. 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. Drugs. 2020;80(6):587-600.

Mohan V, Mithal A, Joshi SR, Aravind SR, Chowdhury S. Remogliflozin Etabonate in the Treatment of Type 2 Diabetes: Design, Development, and Place in Therapy. Drug Des Devel Ther. 2020;14:2487-501.

Heise T, Seewaldt BE, Macha S, Hantel S, Pinnetti S, Seman L, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks' treatment with empagliflozin once daily in patients with type 2 diabetes. Diabetes Obes Metab. 2013;15:613-21.

Heise T, Seman L, Macha S, Jones P, Marquart A, Pinnetti S, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple rising doses of empagliflozin in patients with type 2 diabetes mellitus. Diabetes Ther. 2013;4(2):331-45.

Kasichayanula S, Liu X, Lacreta F, Grifen SC, Boulton DW. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2013;53:17-27.

Devineni D, Polidori D, Curtin C, Stieltjes H, Tian H, Wajs E. Single-dose pharmacokinetics and pharmacodynamics of canagliflozin, a selective inhibitor of sodium-glucose co-transporter 2, in healthy Indian participants. Clin Ther. 2016;38:89-98.

Kapur A, Connor SR, Hussey EK, Dobbins RL, Tao W, Hompesch M, et al. First dose-escalation study with remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2 (SGLT2), in healthy subjects and in subjects with type 2 diabetes mellitus. BMC Pharmacol Toxicol. 2013;14:26.

American Diabetes Association. Glycemic Targets: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019;42(1):61-70.

Indian Council of Medical Research. Guidelines for the management of type 2 diabetes patients, 2018. Available at: https://medibulletin.com/wp-content/uploads/2018/05/ICMR.diabetesGuidelines.2018. Accessed on 10 August 2020.

Sykes AP, Kemp GL, Dobbins R, Connor SR, Almond SR, Wilkison WO, et al. Randomized efficacy and safety trial of once-daily remogliflozin etabonate for the treatment of type 2 diabetes. Diabetes Obes Metab. 2015;98-101.

Sykes AP, Connor SR, Dobbins R, Dorey DJ, Lorimer JD, Walker S, et al. Randomized trial showing efficacy and safety of twice-daily remogliflozin etabonate for the treatment of type 2 diabetes. Diabetes Obes Metab. 2015;17:94-7.

Gill HK, Kaur P, Mahendru S, Mithal A. Adverse Effect Profile and Effectiveness of Sodium Glucose Co-transporter 2 Inhibitors (SGLT2i) - A Prospective Real-world Setting Study. Indian J Endocrinol Metab. 2019;23:50-5.

Ito Y, Schyndle JV, Nishimura T, Sugitani T, Kimura T. Real-World Effectiveness of Sodium Glucose Co-Transporter-2 Inhibitors in Japanese Patients with Diabetes Mellitus. Diabetes Ther. 2019;10:2219-31.

Thewjitcharoen Y, Yenseung N, Malidaeng A, Nakasatien S, Chotwanvirat P, Krittiyawong S, et al. Efectiveness of long-term treatment with SGLT2 inhibitors: real-world evidence from a specialized diabetes center. Diabetol Metab Syndr. 2017;9:96.

Giugliano D, Maiorino M, Bellastella G, Chiodini P, Esposito K. Relationship of baseline HbA1c, HbA1c change and HbA1c target of <7% with insulin analogues in type 2 diabetes: a metaanalysis of randomised controlled trials. Int J Clin Pract. 2011;65:602-12.

Brown RE, Gupta N, Aronson R. Effect of dapagliflozin on glycemic control, weight, and blood pressure in patients with type 2 diabetes attending a specialist endocrinology practice in Canada: a retrospective cohort analysis. Diabetes Technol Ther. 2017;19:685-91.

Wilding J, Godec T, Khunti K, Pocock S, Fox R, Smeeth L, et al. Changes in HbA1c and weight, and treatment persistence, over the 18 months following initiation of second-line therapy in patients with type 2 diabetes: results from the United Kingdom Clinical Practice Research Datalink. Bio Med Centr Med. 2018;16:116.

Viswanathan V, Singh KP. Use of Dapagliflozin in the Management of Type 2 Diabetes Mellitus: A Real-World Evidence Study in Indian Patients (FOREFRONT). Diabetes Technol Ther. 2019;21(8):415-22.

Madaan T, Akhtar M, Najmi AK. Sodium glucose Co Transporter 2 (SGLT2) inhibitors: current status and future perspective. Eur J Pharm Sci. 2016;93:244-52.

Leiter LA, Langslet G, Vijapurkar U, Davies MJ, Canovatchel W. Simultaneous reduction in both HbA1c and body weight with canagliflozin versus glimepiride in patients with type 2 diabetes on metformin. Diabetes Ther. 2016;7:269-78.

John M, Cerdas S, Violante R, Deerochanawong C, Hassanein M, Slee A, et al. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus living in hot climates. Int J Clin Pract. 2016;70:775-85.

Tamez PHE, Delgadillo EE, Soni DD, Hernandez CMI, Tamez PAL. SGLT2 inhibitors as add on therapy in type 2 diabetes: a real world study. J Diabetes Metab Disord. 2017;16:27.