Acute effects of linagliptin on intact and total glucagon‐like peptide‐1 and gastric inhibitory polypeptide levels in insulin‐dependent type 2 diabetes patients with and without moderate renal impairment

Abstract

Aims: To investigate the effect of renal impairment on incretin metabolism in patients with type 2 diabetes mellitus (T2DM) before and after treatment with the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin.Materials and methods: Long-standing T2DM patients with normal (estimated glomerular filtration rate [eGFR] >90 mL/min/1.73m 2 ) and impaired (eGFR <60 mL/min/1.73m 2 ) renal function on stable treatment with insulin were included. Before and after 8 days of treatment with 5 mg linagliptin once daily, patients underwent a 75-g oral glucose tolerance test (OGTT) and total and intact glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), glucose, insulin, C-peptide and glucagon concentrations were measured. The primary outcome 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/1.73m 2 ; P < 0.0001), while glycaemic control was similar (glycated haemoglobin 68 ± 5 vs. 66 ± 5 mmol/mol; 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 the OGTT.However, the primary outcome (difference between the groups in change of intact GLP-1 concentrations) was not significant (P = 0.22). Overall, linagliptin was well tolerated.Juris J. Meier and Daniel R. Quast contributed equally to this work.