The association between postprandial urinary C-peptide creatinine ratio and the treatment response to liraglutide: a multi-centre observational study

Aims The response to glucagon-like peptide1 receptor agonist treatment may be influenced by endogenous beta-cell function. We investigated whether urinary C-peptide creatinine ratio assessed before or during liraglutide treatment was associated with treatment response. Methods A single, outpatient urine sample for urinary C-peptide creatinine ratio was collected 2h after the largest meal of the day among two separate groups: (1) subjects initiating liraglutide (0.6 -> 1.2mg daily) or (2) subjects already treated with liraglutide for 20-32weeks. The associations between pretreatment and on-treatment urinary C-peptide creatinine ratio and HbA(1c) change at 32weeks were assessed using univariate and multivariate analyses (the ratio was logarithm transformed for multivariate analyses). Changes in HbA(1c) according to pretreatment urinary C-peptide creatinine ratio quartiles are shown. Results One hundred and sixteen subjects (70 pretreatment, 46 on treatment) with Type2 diabetes from 10 diabetes centres were studied. In univariate analyses, neither pretreatment nor on-treatment urinary C-peptide creatinine ratio correlated with HbA(1c) change (Spearman rank correlation coefficient, r=-0.17, P=0.17 and r=-0.20, P=0.19, respectively). In multi-linear regression analyses, entering baseline HbA(1c) and log urinary C-peptide creatinine ratio, pretreatment and on-treatment log urinary C-peptide creatinine ratio became significantly associated with HbA(1c) change (P=0.048 and P=0.040, respectively). Mean (sd) HbA(1c) changes from baseline in quartiles1 to 4 of pretreatment urinary C-peptide creatinine ratio were -3 +/- 17mmol/mol (-0.3 +/- 1.6%) (P=0.52), -12 +/- 15mmol/mol (-1.1 +/- 1.4%) (P=0.003), -11 +/- 13mmol/mol (-1.0 +/- 1.2%) (P=0.002) and -12 +/- 17mmol/mol (-1.1 +/- 1.6%) (P=0.016), respectively. Conclusions Postprandial urinary C-peptide creatinine ratios before and during liraglutide treatment were weakly associated with the glycaemic response to treatment. Low pretreatment urinary C-peptide creatinine ratio may be more useful than higher values by predicting poorer glycaemic response.