Ryota Usui1, Daisuke Yabe2, Hitoshi Kuwata3, Kenta Murotani4, Takeshi Kurose3, Yutaka Seino5. 1. Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka, 553-0003, Japan. 2. Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka, 553-0003, Japan; Center for Metabolism and Clinical Nutrition, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka, 553-0003, Japan; Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, 2-1-7 Fukushima-ku, Osaka, 553-0003, Japan; Division of Molecular and Metabolic Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 1-5-6 Minatojimaminamimachi, Chuo-ku, Kobe, 650-0047, Japan. Electronic address: ydaisuke-kyoto@umin.ac.jp. 3. Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka, 553-0003, Japan; Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, 2-1-7 Fukushima-ku, Osaka, 553-0003, Japan. 4. Center for Clinical Research, Aichi University Hospital, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan. 5. Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka, 553-0003, Japan; Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, 2-1-7 Fukushima-ku, Osaka, 553-0003, Japan. Electronic address: seino.yutaka@e2.kepco.co.jp.
Abstract
AIMS: The GLP-1 receptor agonist liraglutide improves impaired pancreatic β-cell function, thereby exerting glucose-lowering effects. However, the association of remaining β-cell function with long-term therapeutic efficacy of liraglutide remains largely unknown. METHODS: Patients with type 2 diabetes who started liraglutide as monotherapy or sulfonylurea-combination therapy were retrospectively analyzed to identify possible associations of indices related to β-cell function including increments of C-peptide immunoreactivity in glucagon stimulation test (GST-ΔCPR) with achievement of HbA1c <7.0% at 54weeks after liraglutide initiation. RESULTS: Among 165 subjects continuing liraglutide for 54weeks, 66 received additional oral anti-diabetic drugs (OADs) during the period. Of those continuing liraglutide without receiving additional OADs, 41 subjects achieved HbA1c <7.0% at 54weeks, while 49 subjects did not. Subjects achieving HbA1c <7.0% showed higher values of GST-ΔCPR. Receiver-operating analysis revealed 2.34ng/mL as the cut-off value for HbA1c <7.0% achievement in these subjects. Subjects with GST-ΔCPR >2.34ng/mL showed continuous and substantial HbA1c reduction throughout the 54weeks. In Kaplan-Meier analysis, subjects with GST-ΔCPR >2.34ng/mL showed longer therapeutic durability of initial liraglutide therapy with no additional OADs or insulin. CONCLUSIONS: Despite numerous limitations, these results indicate that long-term efficacy of liraglutide is associated with remaining β-cell function at initiation.
AIMS: The GLP-1 receptor agonist liraglutide improves impaired pancreatic β-cell function, thereby exerting glucose-lowering effects. However, the association of remaining β-cell function with long-term therapeutic efficacy of liraglutide remains largely unknown. METHODS:Patients with type 2 diabetes who started liraglutide as monotherapy or sulfonylurea-combination therapy were retrospectively analyzed to identify possible associations of indices related to β-cell function including increments of C-peptide immunoreactivity in glucagon stimulation test (GST-ΔCPR) with achievement of HbA1c <7.0% at 54weeks after liraglutide initiation. RESULTS: Among 165 subjects continuing liraglutide for 54weeks, 66 received additional oral anti-diabetic drugs (OADs) during the period. Of those continuing liraglutide without receiving additional OADs, 41 subjects achieved HbA1c <7.0% at 54weeks, while 49 subjects did not. Subjects achieving HbA1c <7.0% showed higher values of GST-ΔCPR. Receiver-operating analysis revealed 2.34ng/mL as the cut-off value for HbA1c <7.0% achievement in these subjects. Subjects with GST-ΔCPR >2.34ng/mL showed continuous and substantial HbA1c reduction throughout the 54weeks. In Kaplan-Meier analysis, subjects with GST-ΔCPR >2.34ng/mL showed longer therapeutic durability of initial liraglutide therapy with no additional OADs or insulin. CONCLUSIONS: Despite numerous limitations, these results indicate that long-term efficacy of liraglutide is associated with remaining β-cell function at initiation.