Randomized, double-blind, placebo-controlled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea (GetGoal-L-Asia)

Y Seino, K W Min, E Niemoeller, A Takami, EFC10887 GETGOAL-L Asia Study Investigators, Nobuyuki Abe, Keiko Arai, Tsuguyoshi Asano, Atsushi Hasegawa, Toru Hiyoshi, Toshihiko Inoue, Yukinori Isomura, Sizuka Kaneko, Tadashu Kasahara, Zenji Makita, Kiyokazu Matoba, Hiroaki Miyaoka, Tetsuji Niiya, Keiichiro Nishino, Katsumi Noda, Akira Okada, Yukiko Onishi, Takeshi Osonoi, Mitsuru Ozaki, Masatomo Sekiguchi, Toshihiko Shiraiwa, Hidekatsu Sugimoto, Yoshihiko Suzuki, Toru Takeuchi, Tsuyoshi Tanaka, Miki Tateyama, Osamu Tomonaga, Hiroshi Uchino, Nobuaki Watanabe, Shuichi Watanabe, Takayuki Watanabe, Akira Yamauchi, Tatsuo Yanagawa, Maria Honolina Gomez, Araceli Panelo, Rosa Allyngsy, Ernesto L Ang, Hong-Sun Baek, H Choon Chung, Hak C Jang, Dong-Jun Kim, In J Kim, Kwang-Won Kim, Yong S Kim, Hyun Chul Lee, Ji Hyun Lee, Kwan-Woo Lee, Wan Min Kyung, Chul Woo Anh, Doo Man Kim, Ie B Park, Minho Shong, Young D Song, Hyun Shik Son, Ki-Ho Song, Kyu C Won, Jae M Yu, Y Seino, K W Min, E Niemoeller, A Takami, EFC10887 GETGOAL-L Asia Study Investigators, Nobuyuki Abe, Keiko Arai, Tsuguyoshi Asano, Atsushi Hasegawa, Toru Hiyoshi, Toshihiko Inoue, Yukinori Isomura, Sizuka Kaneko, Tadashu Kasahara, Zenji Makita, Kiyokazu Matoba, Hiroaki Miyaoka, Tetsuji Niiya, Keiichiro Nishino, Katsumi Noda, Akira Okada, Yukiko Onishi, Takeshi Osonoi, Mitsuru Ozaki, Masatomo Sekiguchi, Toshihiko Shiraiwa, Hidekatsu Sugimoto, Yoshihiko Suzuki, Toru Takeuchi, Tsuyoshi Tanaka, Miki Tateyama, Osamu Tomonaga, Hiroshi Uchino, Nobuaki Watanabe, Shuichi Watanabe, Takayuki Watanabe, Akira Yamauchi, Tatsuo Yanagawa, Maria Honolina Gomez, Araceli Panelo, Rosa Allyngsy, Ernesto L Ang, Hong-Sun Baek, H Choon Chung, Hak C Jang, Dong-Jun Kim, In J Kim, Kwang-Won Kim, Yong S Kim, Hyun Chul Lee, Ji Hyun Lee, Kwan-Woo Lee, Wan Min Kyung, Chul Woo Anh, Doo Man Kim, Ie B Park, Minho Shong, Young D Song, Hyun Shik Son, Ki-Ho Song, Kyu C Won, Jae M Yu

Abstract

Aims: To assess the efficacy and safety of once-daily lixisenatide versus placebo in Asian patients with type 2 diabetes insufficiently controlled on basal insulin ± sulfonylurea.

Methods: In this 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicentre study, participants (mean baseline HbA(1c) 8.53%) from Japan, Republic of Korea, Taiwan and the Philippines received lixisenatide (n = 154) or placebo (n = 157) in a stepwise dose increase to 20 µg once daily. The primary endpoint was HbA(1c) change from baseline to week 24.

Results: Once-daily lixisenatide significantly improved HbA(1c) versus placebo (LS mean difference vs. placebo = -0.88% [95%CI= -1.116, -0.650]; p < 0.0001), and allowed more patients to achieve HbA(1c) <7.0% (35.6 vs. 5.2%) and ≤ 6.5% (17.8 vs. 1.3%). Lixisenatide also significantly improved 2-h postprandial plasma glucose and glucose excursion, average 7-point self-monitored blood glucose and fasting plasma glucose. Lixisenatide was well tolerated; 86% of patients on lixisenatide completed the study versus 92% on placebo. Ten (6.5%) lixisenatide and 9 (5.7%) placebo patients experienced serious adverse events. More lixisenatide patients [14 (9.1%)] discontinued for adverse events versus placebo [5 (3.2%)], mainly with gastrointestinal causes. Nausea and vomiting were reported in 39.6 and 18.2% of patients on lixisenatide versus 4.5 and 1.9% on placebo. Symptomatic hypoglycaemia was more frequent with lixisenatide (42.9%) versus placebo (23.6%), but was similar between groups (32.6 vs. 28.3%, respectively), in those not receiving sulfonylureas. No severe hypoglycaemia was reported.

Conclusions: In an Asian type 2 diabetes population insufficiently controlled by basal insulin ± sulfonylurea, once-daily lixisenatide significantly improved glycaemic control, with a pronounced postprandial effect, and was well tolerated.

© 2012 Blackwell Publishing Ltd.

Figures

Figure 1
Figure 1
Glycated hemoglobin (HbA1c) levels after 24 weeks. (A) Mean (± s.e.) HbA1c over time. (B) Percentage of patients achieving HbA1c goals <7.0% and ≤6.5%; *LS mean change in HbA1c at week 24, LOCF data. mITT population.
Figure 2
Figure 2
Changes in post-meal glucose parameters from baseline after 24 weeks. Change in LS mean (±s.e.) 2-h postprandial plasma glucose (PPG) levels and change in LS mean (±s.e.) 2-h glucose excursion (2-h PPG – plasma glucose 30 min prior to meal test, prior to injection). LOCF data. mITT population.

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Source: PubMed

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