Liraglutide is effective in type 2 diabetic patients with sustained endogenous insulin‐secreting capacity

Abstract

Aims/Introduction: Recently, glucagon‐like peptide‐1 (GLP‐1) receptor agonists of liraglutide have become available in Japan. It has not yet been clarified what clinical parameters could discriminate liraglutide‐effective patients from liraglutide‐ineffective patients.Materials and Methods: We reviewed 23 consecutive patients with type 2 diabetes admitted to Osaka University Hospital for glycemic control. All of the patients were treated with diet plus insulin (or plus oral antidiabetic drugs) to improve fasting plasma glucose (FPG) and postprandial glucose below 150 and 200 mg/dL, respectively. After insulin secretion and insulin resistance were evaluated, insulin was replaced by liraglutide. The efficacy of liraglutide was determined according to whether glycemic control was maintained at the target levels.Results: Liraglutide was effective in 13 of 23 patients. There were significant differences in the parameters of insulin secretion, including fasting C‐peptide (F‐CPR), C‐peptide index (CPI), insulinogenic index (I.I.) and urine C‐peptide (U‐CPR), between liraglutide‐effective and ‐ineffective patients. The duration of diabetes was significantly shorter in liraglutide‐effective patients than in liraglutide‐ineffective patients. In receiver operating characteristic analyses, the cut‐off value for predicting the efficacy of liraglutide was 0.14 for I.I., 1.1 for CPI, 1.5 ng/mL for F‐CPR, 33.3 μg/day for U‐CPR and 19.5 years for duration of type 2 diabetes.Conclusions: Insulin secretion evaluated by F‐CPR, CPI, I.I., U‐CPR and the duration of type 2 diabetes were useful parameters for predicting the efficacy of liraglutide in patients with type 2 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00168.x, 2011)

Insulin treatment and longer diabetes duration both predict poorer glycaemic response to liraglutide treatment in type 2 diabetes: the Association of British Clinical Diabetologists Nationwide Liraglutide Audit

“…13 Our findings might suggest that the therapeutic response to liraglutide may be influenced by background β-cell function, for which background diabetes treatment and duration of diabetes may act as surrogate markers. Consistent with this view, studies have shown that higher C-peptide secretion is predictive of a larger treatment response to liraglutide, 12,14 or a greater likelihood of success when switching patients to liraglutide from insulin. 15,16 The mean reduction in HbA1c with liraglutide was smaller for patients treated with insulin, relative to patients receiving other therapies, but nevertheless remained clinically significant.…”

“…11 Longer diabetes duration predicted a poorer glycaemic response to liraglutide therapy in our study, and is consistent with findings of a meta-analysis of the LEAD studies 4 and a report from a small observational study. 12 In contrast, in a trial consisting only of patients on insulin, glycaemic reduction with the addition of exenatide twice daily was greater among patients with longer rather than shorter duration of disease. 13 Our findings might suggest that the therapeutic response to liraglutide may be influenced by background β-cell function, for which background diabetes treatment and duration of diabetes may act as surrogate markers.…”

Postprandial serum C‐peptide value is the optimal index to identify patients with non‐obese type 2 diabetes who require multiple daily insulin injection: Analysis of C‐peptide values before and after short‐term intensive insulin therapy

“…Incretin agents, unlike other antidiabetic agents, exert GLP-1 effects on glucose-dependent insulin secretion and pancreatic b-cell protection 24 , and thus might influence selection of patients for insulin therapy in type 2 diabetes. Kozawa et al 25 reported, however, that patients with decreased insulin secretion showed lowered efficacy of GLP-1 receptor agonist, liraglutide. An exploratory study 26 using another GLP-1 receptor agonist, exenatide, showed that insulin-treated type 2 diabetes deteriorated in glucose control in 38% of the patients who switched from insulin to exenatide.…”

Early liraglutide treatment improves β-cell function in patients with type 2 diabetes: a retrospective cohort study

“…Better outcomes of liraglutide therapy in patients with shorter diabetes durations have been documented in previous reports focusing on residual β-cell function and the effectiveness of liraglutide for lowering glucose levels [7][8][9]. In addition, exenatide has been reported to improve β-cell function in newly or recently diagnosed patients with T2D [37][38][39].…”

“…related to the preservation of adequate β-cell function in patients with T2D [7][8][9][10]. Preclinical studies with liraglutide have suggested protective effects on β cells, including reduced apoptosis and enhanced β-cell proliferation in both rodent models and humans [11][12][13][14][15][16][17].…”