Safety and Effectiveness of Tofogliflozin in Japanese Patients with Type 2 Diabetes Mellitus Treated in Real-world Clinical Practice: Results of a 36-month Post-marketing Surveillance Study (J-STEP/LT)

Overview

Journal J Diabetes Investig

Specialty Endocrinology

Date 2020 Jun 30

PMID 32597517

Citations 8

Authors

Kazunori Utsunomiya

Ryusuke Koshida

Seigo Kakiuchi

Masayuki Senda

Shoko Fujii

Yuji Kurihara

Ryoji Gunji

Kohei Kaku

Affiliations

Soon will be listed here.

Abstract

Aims/introduction: Tofogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that lowers plasma glucose levels by enhancing urinary glucose excretion. After its approval in Japan in 2014 for the treatment of type 2 diabetes mellitus, we carried out a 3-year prospective observational post-marketing surveillance study in Japanese patients (Japanese Study of Tofogliflozin with Type 2 Diabetes Mellitus Patients/Long Term [J-STEP/LT]).

Materials And Methods: This surveillance was carried out between September 2014 and February 2019, and recorded safety in terms of adverse drug reactions (ADRs) and ADRs of special interest, and effectiveness in terms of changes in glycated hemoglobin and bodyweight from baseline to last observation carried forward.

Results: Of 6,897 patients with type 2 diabetes mellitus registered, 6,711 and 6,451 were analyzed for safety and effectiveness, respectively. ADRs were reported in 846 patients (12.61%), with serious ADRs in 101 patients (1.5%). ADRs of special interest included hypoglycemia (62 patients [0.9%]), polyuria/pollakiuria (90 [1.3%]), volume depletion-related disorders (135 [2.0%]), urinary tract infections (91 [1.4%]), genital infections (117 [1.7%]) and skin diseases (53 [0.8%]). One case of diabetic ketoacidosis was reported. The mean ± standard deviation changes from baseline to last observation carried forward in glycated hemoglobin and bodyweight were -0.68 ± 1.34% (n = 6,158, P < 0.0001) and -3.13 ± 4.67 kg (n = 5,213, P < 0.0001), respectively.

Conclusions: J-STEP/LT, a 3-year, prospective, observational, post-marketing study in Japan, found no unprecedented ADRs, and consistent reductions from baseline in glycated hemoglobin and bodyweight over the observation period. The present results provide further evidence regarding the safety and tolerability of tofogliflozin in Japanese patients with type 2 diabetes mellitus.

Citing Articles

Safety and effectiveness of tofogliflozin in Japanese people with type 2 diabetes: A multicenter prospective observational study in routine clinical practice.

Yamada Y, Yabe D, Shide K, Suzuki A, Terauchi Y, Sato Y J Diabetes Investig. 2024; 15(11):1585-1595.

PMID: 39141404 PMC: 11527805. DOI: 10.1111/jdi.14287.

The Efficacy and Safety of Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitors in Real-World Clinical Practice: Potential Cautionary Use in Elderly Patients with Type 2 Diabetes (T2D).

Lee D, Oh J, Jeon H, Oh T Diabetes Ther. 2024; 15(7):1615-1626.

PMID: 38771472 PMC: 11211288. DOI: 10.1007/s13300-024-01604-8.

Reasons for Discontinuing Treatment with Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Diabetes in Real-World Settings: The KAMOGAWA-A Study.

Saijo Y, Okada H, Hata S, Nakajima H, Kitagawa N, Okamura T J Clin Med. 2023; 12(22).

PMID: 38002608 PMC: 10672375. DOI: 10.3390/jcm12226993.

Changes in the estimated glomerular filtration rate and predictors of the renal prognosis in Japanese patients with type 2 diabetes: A retrospective study during the 12 months after the initiation of tofogliflozin.

Ito H, Inoue H, Izutsu T, Matsumoto S, Antoku S, Yamasaki T PLoS One. 2023; 18(9):e0292014.

PMID: 37733761 PMC: 10513294. DOI: 10.1371/journal.pone.0292014.

Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials.

Li C, Liu L, Zhang C, Geng X, Gu S, Wang Y Front Endocrinol (Lausanne). 2023; 14:1238399.

PMID: 37701900 PMC: 10494439. DOI: 10.3389/fendo.2023.1238399.

References

Fujita Y, Inagaki N . Update on the efficacy and safety of sodium-glucose cotransporter 2 inhibitors in Asians and non-Asians. J Diabetes Investig. 2019; 10(6):1408-1410. PMC: 6825932. DOI: 10.1111/jdi.13150. View

Kaku K, Chin R, Naito Y, Iliev H, Ikeda R, Ochiai K . Safety and effectiveness of empagliflozin in Japanese patients with type 2 diabetes: interim analysis from a post-marketing surveillance study. Expert Opin Drug Saf. 2019; 19(2):211-221. DOI: 10.1080/14740338.2020.1694659. View

Terauchi Y, Tamura M, Senda M, Gunji R, Kaku K . Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J-STEP/INS): Results of a 16-week randomized, double-blind, placebo-controlled multicentre trial. Diabetes Obes Metab. 2017; 19(10):1397-1407. PMC: 5637911. DOI: 10.1111/dom.12957. View

Wiviott S, Raz I, Bonaca M, Mosenzon O, Kato E, Cahn A . Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2018; 380(4):347-357. DOI: 10.1056/NEJMoa1812389. View

Moen M, Zhan M, Hsu V, Walker L, Einhorn L, Seliger S . Frequency of hypoglycemia and its significance in chronic kidney disease. Clin J Am Soc Nephrol. 2009; 4(6):1121-7. PMC: 2689888. DOI: 10.2215/CJN.00800209. View

Utsunomiya K, Shimmoto N, Senda M, Kurihara Y, Gunji R, Fujii S . Safety and effectiveness of tofogliflozin in elderly Japanese patients with type 2 diabetes mellitus: A post-marketing study (J-STEP/EL Study). J Diabetes Investig. 2017; 8(6):766-775. PMC: 5668483. DOI: 10.1111/jdi.12626. View

Abdul-Ghani M, Norton L, DeFronzo R . Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus. Am J Physiol Renal Physiol. 2015; 309(11):F889-900. PMC: 4669360. DOI: 10.1152/ajprenal.00267.2015. View

Donnan J, Grandy C, Chibrikov E, Marra C, Aubrey-Bassler K, Johnston K . Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis. BMJ Open. 2019; 9(1):e022577. PMC: 6361337. DOI: 10.1136/bmjopen-2018-022577. View

Ogawa W, Sakaguchi K . Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J Diabetes Investig. 2016; 7(2):135-8. PMC: 4773669. DOI: 10.1111/jdi.12401. View

10.

Ueda P, Svanstrom H, Melbye M, Eliasson B, Svensson A, Franzen S . Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study. BMJ. 2018; 363:k4365. PMC: 6233755. DOI: 10.1136/bmj.k4365. View

11.

Mahaffey K, Neal B, Perkovic V, de Zeeuw D, Fulcher G, Erondu N . Canagliflozin for Primary and Secondary Prevention of Cardiovascular Events: Results From the CANVAS Program (Canagliflozin Cardiovascular Assessment Study). Circulation. 2017; 137(4):323-334. PMC: 5777572. DOI: 10.1161/CIRCULATIONAHA.117.032038. View

12.

Lega I, Bronskill S, Campitelli M, Guan J, Stall N, Lam K . Sodium glucose cotransporter 2 inhibitors and risk of genital mycotic and urinary tract infection: A population-based study of older women and men with diabetes. Diabetes Obes Metab. 2019; 21(11):2394-2404. DOI: 10.1111/dom.13820. View

13.

Yuan Z, Defalco F, Ryan P, Schuemie M, Stang P, Berlin J . Risk of lower extremity amputations in people with type 2 diabetes mellitus treated with sodium-glucose co-transporter-2 inhibitors in the USA: A retrospective cohort study. Diabetes Obes Metab. 2017; 20(3):582-589. PMC: 5836890. DOI: 10.1111/dom.13115. View

14.

Wanner C, Inzucchi S, Lachin J, Fitchett D, von Eynatten M, Mattheus M . Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016; 375(4):323-34. DOI: 10.1056/NEJMoa1515920. View

15.

Goda M, Yamakura T, Sasaki K, Tajima T, Ueno M . Safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus: a 1-year post-marketing surveillance in Japan. Curr Med Res Opin. 2017; 34(2):319-327. DOI: 10.1080/03007995.2017.1392293. View

16.

Utsunomiya K, Kakiuchi S, Senda M, Fujii S, Kurihara Y, Gunji R . Safety and effectiveness of tofogliflozin in Japanese patients with type 2 diabetes mellitus: Results of 24-month interim analysis of a long-term post-marketing study (J-STEP/LT). J Diabetes Investig. 2020; 11(4):906-916. PMC: 7378444. DOI: 10.1111/jdi.13233. View

17.

Tanizawa Y, Kaku K, Araki E, Tobe K, Terauchi Y, Utsunomiya K . Long-term safety and efficacy of tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2, as monotherapy or in combination with other oral antidiabetic agents in Japanese patients with type 2 diabetes mellitus: multicenter,.... Expert Opin Pharmacother. 2014; 15(6):749-66. DOI: 10.1517/14656566.2014.887680. View

18.

Dave C, Schneeweiss S, Patorno E . Comparative risk of genital infections associated with sodium-glucose co-transporter-2 inhibitors. Diabetes Obes Metab. 2018; 21(2):434-438. PMC: 6329650. DOI: 10.1111/dom.13531. View

19.

Gadzhanova S, Pratt N, Roughead E . Use of SGLT2 inhibitors for diabetes and risk of infection: Analysis using general practice records from the NPS MedicineWise MedicineInsight program. Diabetes Res Clin Pract. 2017; 130:180-185. DOI: 10.1016/j.diabres.2017.06.018. View

20.

Davies M, DAlessio D, Fradkin J, Kernan W, Mathieu C, Mingrone G . Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018; 41(12):2669-2701. PMC: 6245208. DOI: 10.2337/dci18-0033. View