Oral glucose‐stimulated serum C‐peptide predicts successful switching from insulin therapy to liraglutide monotherapy in Japanese patients with type 2 diabetes and renal impairment

Abstract

Aims/IntroductionIn Japan, liraglutide was recently approved for patients with type 2 diabetes. To our knowledge, there are no markers predicting successful switching from insulin therapy to liraglutide monotherapy in Japanese patients with type 2 diabetes and renal impairment. We therefore assessed clinical characteristics predicting successful switching.Materials and MethodsWe analyzed 21 patients with type 2 diabetes and estimated glomerular filtration rates <60 mL/min/1.73 m2 receiving long‐term insulin in Shiga University of Medical Science Hospital, Otsu, Shiga, Japan. Their β‐cell function was assessed by measuring urinary C‐peptide and C‐peptide immunoreactivity (CPR) index, along with glucagon loading and oral glucose tolerance tests. Blood glucose concentration and blood pressure were measured daily before and after switching from insulin to liraglutide, and glycated hemoglobin (HbA1c; National Glycohemoglobin Standardization Program) was assessed 12 weeks after switching to liraglutide.ResultsBaseline HbA1c was significantly lower in successfully switched than in unsuccessfully switched patients. CPR index, urinary C‐peptide concentration and 6‐min post‐glucagon increment in CPR (ΔCPR) did not differ significantly in the two groups. ΔCPR 120 min after 75 g oral glucose was significantly higher in successfully than unsuccessfully switched patients. Mean blood glucose concentrations before breakfast, after breakfast, before lunch and after dinner were significantly lower in successfully switched patients. HbA1c did not change significantly in either group.ConclusionsMeasurement of oral glucose‐stimulated ΔCPR120 min is recommended when considering switching Japanese type 2 diabetes patients with renal impairment from insulin to liraglutide monotherapy.

Retrospective Analysis of an Insulin-to-Liraglutide Switch in Patients with Type 2 Diabetes Mellitus

“…Disease duration and low baseline HbA1c have been shown previously to predict good glycemic control on a GLP-1 RA both after an insulin-to-exenatide switch and after oral antidiabetic medication [ 3 , 11 , 12 ]. In contrast, we did not observe higher levels of C-peptide, a marker of remaining beta cell capacity, in patients that successfully switched to liraglutide as previously described [ 3 – 7 , 11 , 12 ]. However, it should be noted that based on previous studies our institutional guidelines prescribe that all patients considered for a switch need to have C-peptide levels > 0.50 nmol/l (1.50 ng/ml) omitting patients with low C-peptide levels.…”

“…Furthermore, our C-peptide values were not standardized for meal or time of day, causing significant variation. A recent study showed also no relation between response to liraglutide or dulaglutide and fasting C-peptide, whereas previously postprandial C-peptide has been shown to be a better indicator of success [ 6 , 7 , 13 ].…”

“…In patients randomized to switching from insulin to the GLP-1 RA exenatide or maintaining their insulin regimen, exenatide alone was able to sustain glycemic control [ 3 ]. Short-term studies on an insulin-to-liraglutide switch in relatively lean Japanese patients using low doses of liraglutide and no concurrent treatment of metformin or sulfonylurea (SU) showed that 57–75% of the patients continued liraglutide with overall improvement in glycemic control [ 4 – 7 ]. Determinants of success were shorter duration of DM2, lower insulin dose, lower HbA1c levels, and higher C-peptide concentrations at baseline.…”

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

“…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. Recent clinical studies have shown that combinations of GLP-1 agonists and insulin are a rational treatment choice, as the inclusion of the GLP-1 agonist improves antihyperglycaemic efficacy while limiting the weight gain and hypoglycaemia associated with insulin.…”

Diabetes mellitus: in search of an improved classification and treatment algorithm

“…Up to present the role of C-peptide in determining the best timing for the initiation of insulin in a patient with classic T2D has not been clarified and usually it is the clinical course of the disease and not the laboratory results which lead this decision (17). Some studies seemed to indicate fasting and stimulated C-peptide levels of 0.3 nmol/l and 0.6-0.8 nmol/l, respectively as cut-offs for successful insulin withdrawal, suggesting that these values distinguish insulin-requiring vs non-insulin requiring diabetes (18)(19)(20). However, it should be noted that the metabolic control in these studies was less stringent.…”