Efficacy and safety of ipragliflozin as an add-on therapy to sitagliptin and metformin in Korean patients with inadequately controlled type 2 diabetes mellitus: A randomized controlled trial.

Abstract

AIM:

To evaluate the efficacy and safety of ipragliflozin vs placebo as add-on therapy to metformin and sitagliptin in Korean patients with type 2 diabetes mellitus (T2DM).

METHODS:

This double-blind, placebo-controlled, multi-centre, phase III study was conducted in Korea in 2015 to 2017. Patients were randomized to receive either ipragliflozin 50 mg/day or placebo once daily for 24 weeks in addition to metformin and sitagliptin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to end of treatment (EOT).

RESULTS:

In total, 143 patients were randomized and 139 were included in efficacy analyses (ipragliflozin: 73, placebo: 66). Baseline mean (SD) HbA1c levels were 7.90 (0.69)% for ipragliflozin add-on and 7.92 (0.79)% for placebo. The corresponding mean (SD) changes from baseline to EOT were -0.79 (0.59)% and 0.03 (0.84)%, respectively, in favour of ipragliflozin (adjusted mean difference -0.83% [95% CI -1.07 to -0.59]; P < .0001). More ipragliflozin-treated patients than placebo-treated patients achieved HbA1c target levels of <7.0% (44.4% vs 12.1%) and < 6.5% (12.5% vs 1.5%) at EOT (P < .05 for both). Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference -1.64 mmol/L, -1.50 μU/mL, -1.72 kg, and -0.99, respectively; P < .05 for all). Adverse event rates were similar between groups (ipragliflozin: 51.4%; placebo: 50.0%). No previously unreported safety concerns were noted.

CONCLUSIONS:

Ipragliflozin as add-on to metformin and sitagliptin significantly improved glycaemic variables and demonstrated a good safety profile in Korean patients with inadequately controlled T2DM.

• Authors: Kyung-Ah Han, Suk Chon, Choon Hee Chung, Soo Lim, Kwan-Woo Lee, SeiHyun Baik, Chang Hee Jung, Dong-Sun Kim, Kyong Soo Park, Kun-Ho Yoon, In-Kyu Lee, Bong-Soo Cha, Taishi Sakatani, Sumi Park, Moon-Kyu Lee
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 20 Issue 10 Pg. 2408-2415 (10 2018) ISSN: 1463-1326 [Electronic] England
• PMID: 29862619 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Chemical References

• Blood Glucose
• Glucosides
• Glycated Hemoglobin A
• Thiophenes
• ipragliflozin
• Metformin
• Sitagliptin Phosphate

Topics

• Adult
• Aged
• Blood Glucose (drug effects, metabolism)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Glucosides (administration & dosage, adverse effects)
• Glycated Hemoglobin (drug effects, metabolism)
• Humans
• Male
• Metformin (administration & dosage, adverse effects)
• Middle Aged
• Republic of Korea
• Sitagliptin Phosphate (administration & dosage, adverse effects)
• Thiophenes (administration & dosage, adverse effects)
• Treatment Outcome
• Young Adult