Comprehensive Evaluation of Combination Therapy with Basal Insulin and Either Lixisenatide or Vildagliptin in Japanese Patients with Type 2 Diabetes: A Randomized, Open-Label, Parallel-Group, Multicenter Study

Natsu Otowa-Suematsu; Kazuhiko Sakaguchi; Tomoaki Nakamura; Kenta Hara; Minoru Kishi; Naoko Hashimoto; Kazuki Yokota; Hiroshi Yoshino; Yasuo Kuroki; Tomoko Nishiumi; Anna Sou; Hisako Komada; Yuko Okada; Yushi Hirota; Yoshikazu Tamori; Wataru Ogawa

doi:10.1007/s13300-018-0505-2

Comprehensive Evaluation of Combination Therapy with Basal Insulin and Either Lixisenatide or Vildagliptin in Japanese Patients with Type 2 Diabetes: A Randomized, Open-Label, Parallel-Group, Multicenter Study

Diabetes Ther. 2018 Oct;9(5):2067-2079. doi: 10.1007/s13300-018-0505-2. Epub 2018 Sep 11.

Authors

Natsu Otowa-Suematsu¹, Kazuhiko Sakaguchi^{2

3}, Tomoaki Nakamura¹, Kenta Hara⁴, Minoru Kishi⁵, Naoko Hashimoto⁶, Kazuki Yokota⁷, Hiroshi Yoshino⁸, Yasuo Kuroki⁹, Tomoko Nishiumi¹⁰, Anna Sou¹, Hisako Komada¹, Yuko Okada¹, Yushi Hirota¹, Yoshikazu Tamori^{1

11}, Wataru Ogawa¹

Affiliations

¹ Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
² Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. kzhkskgc@med.kobe-u.ac.jp.
³ Division of General Internal Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. kzhkskgc@med.kobe-u.ac.jp.
⁴ Department of Diabetes and Endocrine disease, Kita-harima Medical Center, Ono, Japan.
⁵ Department of Internal Medicine, Nishiwaki Municipal Hospital, Nishiwaki, Japan.
⁶ Department of Diabetes and Endocrinology, Hyogo Brain and Heart Center, Himeji, Japan.
⁷ Department of Internal Medicine, Jinkeikai Ishii Hospital, Akashi, Japan.
⁸ Department of Internal Medicine, Shinsuma General Hospital, Kobe, Japan.
⁹ Department of Internal Medicine, Kobe Century Memorial Hospital, Kobe, Japan.
¹⁰ Department of Diabetes and Endocrinology, Kobe Rosai Hospital, Kobe, Japan.
¹¹ Division of Creative Health Promotion, Department of Social/Community Medicine and Health Science, Kobe University Graduate School of Medicine, Kobe, Japan.

Abstract

Introduction: We comprehensively evaluated the effects of combination therapy with insulin glargine and the incretin-based drugs lixisenatide or vildagliptin in Japanese patients with type 2 diabetes.

Methods: In this 12-week, randomized, open-label, parallel-group, multicenter study (GLP-ONE Kobe), the incretin-based drug sitagliptin was randomly switched to lixisenatide (20 μg/day, n = 18) or vildagliptin (100 mg/day, n = 20) in patients with inadequate glycemic control despite combination therapy with insulin glargine and sitagliptin. The dose of insulin glargine was titrated after the switch to maintain fasting blood glucose at approximately 110 mg/dL. The primary end points of the study were the change in glycosylated hemoglobin (HbA_1c) level between before and 12 weeks after the treatment switch, the proportion of patients achieving an HbA_1c level below 7.0%, and the postprandial increase in glucose concentration as assessed by self-monitoring of blood glucose.

Results: The change in HbA_1c level from baseline to 12 weeks did not differ significantly between the lixisenatide and vildagliptin groups (- 0.6 ± 0.7% and - 0.6 ± 1.2%, respectively, P = 0.920). Neither the proportion of patients achieving an HbA_1c level below 7.0% nor the postprandial increase in glucose concentration was different between two groups. Body weight and serum low density lipoprotein (LDL) cholesterol level decreased significantly in the lixisenatide and vildagliptin groups, respectively. Both drugs were associated with mild gastrointestinal symptoms but not with severe hypoglycemia. Vildagliptin was associated with elevation of serum aspartate transaminase. Treatment satisfaction as assessed with the Diabetes Treatment Satisfaction Questionnaire did not differ significantly between the two groups.

Conclusion: The combinations of basal insulin and either lixisenatide or vildagliptin have similar efficacies with regard to improvement of glycemic control.

Trial registration: This trial has been registered with UMIN (No. 000010769).

Keywords: Insulin glargine; Lixisenatide; Vildagliptin.