Aims

Impaired renal function is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The goal of this study was to investigate the effect of renal impairment on incretin metabolism in patients with T2DM before and after treatment with the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin.

Materials and methods

Long-standing T2DM patients with normal (eGFR>90ml/min/1.73m2) and impaired (eGFR<60ml/min/1.73m2) renal function on stable treatment with insulin were included. Before and after eight days of treatment with 5mg linagliptin once daily, patients underwent an 75g oral glucose test (OGTT) and total and intact GLP-1 and GIP, glucose, insulin, C-peptide, and glucagon concentrations were measured. Primary outcome parameter was the difference between the study groups in change of intact GLP-1 concentrations

Results

Of 115 patients screened, 29 were analysed (15(51.7%) with and 14(48.3%) without renal impairment). Renal function differed significantly between the groups (101±11 vs. 47±13 ml/min/1.73m2, p<0.0001) while glycaemic control was similar (HbA1C 7.9±0.6 vs. 7.7±0.6 %, p=0.45). Baseline GLP-1 and GIP levels were comparable. Glucose concentrations during the OGTT were significantly lowered by linagliptin treatment in patients with renal impairment (p=0.017), but not in those with normal renal function (p=0.17). Treatment with linagliptin resulted in a significant increase in intact GLP-1 and GIP levels in patients with normal (p=0.048 and p=0.0001, respectively) and impaired (p=0.040 and p=0.0011, respectively) renal function during OGTT. However, the primary outcome parameter (difference between the groups in change of intact GLP-1 concentrations) was not significant (P=0.22). Overall, linagliptin was well tolerated.

Conclusions

Treatment with linagliptin increases intact incretin levels in patients with T2DM. Impaired renal function does not compromise the effects of linagliptin on active or total incretin levels as well as on glucagon secretion. Thus, treatment with linagliptin is suitable for patients with T2DM, independently of renal function.

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