Efficacy and safety of luseogliflozin as monotherapy in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, phase 3 study.
OBJECTIVE
Luseogliflozin--a novel, orally bioavailable, 1-thio-D-glucitol derivative and a selective sodium glucose cotransporter 2 inhibitor--has shown efficacy and tolerability in previous phase 2 studies. This phase 3, randomized, double-blind, placebo-controlled, comparative study aimed to confirm the superiority of 24 week luseogliflozin 2.5 mg monotherapy over placebo in reducing hemoglobin A1c (HbA1c) levels in Japanese patients with type 2 diabetes mellitus (T2DM).


METHODS
Patients with HbA1c levels of 6.9%-10.5% were randomized to receive luseogliflozin 2.5 mg or placebo once daily for 24 weeks (n = 79 in each group). The primary endpoint was change from baseline in HbA1c at end of treatment. Secondary endpoints included change from baseline in fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) following a meal tolerance test, body weight, and abdominal circumference. Safety assessments included adverse events (AEs), clinical laboratory tests, and vital signs.


RESULTS
At the end of treatment, HbA1c was significantly decreased from baseline in the luseogliflozin 2.5 mg group (-0.63%) versus the placebo group (0.13%), with a between-group difference of -0.75% (p < 0.001). Additionally, significant reductions in FPG, PPG, body weight, and abdominal circumference were noted with luseogliflozin compared with placebo (all p < 0.05). Luseogliflozin was well tolerated; there was no significant difference between groups in the incidence of AEs (luseogliflozin, 59.5%; placebo, 57.0%). No AEs led to study drug discontinuation. Most AEs were mild in severity, with no severe AE reported. Limitations of this study include its short study duration and small sample size.


CONCLUSIONS
Luseogliflozin monotherapy for 24 weeks was superior to placebo in reducing HbA1c levels. It also reduced FPG, PPG, body weight, and abdominal circumference and was well tolerated in Japanese patients with T2DM.


BACKGROUND
JapicCTI-111661.
Kansai Electric Power Hospital , Osaka , Japan.
Yutaka
Y
Seino
Takashi
T
Sasaki
Atsushi
A
Fukatsu
Michito
M
Ubukata
Soichi
S
Sakai
Yoshishige
Y
Samukawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D015431:Weight Loss
D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D013012:Sorbitol; C517652:hemoglobin A1c protein, human; C549343:1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol
Japanese; Luseogliflozin; Monotherapy; Phase 3 clinical study; Placebo-controlled; Sodium glucose cotransporter 2 inhibitor; Type 2 diabetes mellitus