Retrospective analysis of safety and efficacy of liraglutide monotherapy and sulfonylurea-combination therapy in Japanese type 2 diabetes: Association of remaining β-cell function and achievement of HbA1c target one year after initiation.
OBJECTIVE
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.
Center for Diabetes, Endocrinology, and Metabolism, Kansai Electric Power Hospital, 2-1-7 Fukushima-ku, Osaka, 553-0003, Japan.
Ryota
R
Usui
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.
Daisuke
D
Yabe
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.
Hitoshi
H
Kuwata
Center for Clinical Research, Aichi University Hospital, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Kenta
K
Murotani
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.
Takeshi
T
Kurose
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.
Yutaka
Y
Seino
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D016903:Drug Monitoring; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D054795:Incretins / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007564:Japan; D053208:Kaplan-Meier Estimate; D000069450:Liraglutide / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012189:Retrospective Studies; D013453:Sulfonylurea Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D000069450:Liraglutide; D013453:Sulfonylurea Compounds; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C517652:hemoglobin A1c protein, human
C-peptide; GLP-1 receptor agonist; Glucagon stimulation test; Type 2 diabetes; β-Cell function