Program

PO2-7-31

Comparisons of sodium-glucose cotransporter 2 inhibitors-induced adverse reactions between Japanese and non-Japanese patients: a pooled analysis of randomized controlled trials

[Speaker] Toshiki Hayase:1
[Co-author] Mayu Kobayashi:1, Kaori Ambe:1, Masahiro Tohkin:1
1:Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan

[INTRODUCTION]
Sodium-glucose co-transporter 2 inhibitor (SGLT2-i) is the oral antidiabetic drug for type 2 diabetes (T2DM). To date, six SGLT2-i have been approved in Japan (canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, luseogliflozin, tofogliflozin). In the EMPA-REG OUTCOME trial, empagliflozin which was added on the standard drug reduced the risk of cardiovascular events by 14% in patients with T2DM compared with the placebo group, and subgroup analysis reported that empagliflozin reduced the risk of cardiovascular events by 32% in Asian patients with T2DM compared with the placebo group. In this study, we aimed to compare the frequencies of adverse reactions in addition to the risk of cardiovascular events of SGLT2-i between the Japanese and the non-Japanese patient by using the pooled clinical trials data.

[METHODS]
We extracted the adverse reaction data from common technical documents published by Pharmaceuticals and Medical Devices Agency (PMDA). For placebo-controlled randomized trials in adult patients with T2DM, data for at least 12 weeks of treatment and once-daily of intervention had been assessed. We added up the event numbers of genital tract infections, hypertension, hypoglycemia, major adverse cardiovascular events (MACE: composite of heart failure, myocardial infarction, stroke, angina pectoris), skin disorders, and urinary tract infections, respectively, and then calculated each relative risk ratio.

[RESULTS]
There was a significantly higher risk of genital tract infections in the SGLT2-i group than in the placebo group, and the significantly lower risk of hypertension was observed in the SGLT2-i group. These two adverse reactions showed the similar trend both in the Japanese and the non-Japanese patient. On the other hand, the risk of skin disorders was increased in the SGLT2-i-treated non-Japanese patient only. The risks of MACE were lower in the SGLT2-i group in the Japanese and in the non-Japanese patient although it was not statistically significant in the Japanese patient.
 
[CONCLUSION]
In the SGLT2-i-treated-group, the risk of genital tract infections was increased, and the risk of hypertension was decreased, both in the Japanese and the non-Japanese patient. It was suggested that the reduction in the risk of MACE was similar in the Japanese and the non-Japanese patient.
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