TY  - JOUR
A1  - Hocher, Berthold
A1  - Reichetzeder, Christoph
A1  - Alter, Markus L.
T1  - Renal and cardiac effects of DPP-4 inhibitors - from preclinical development to clinical research
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Inhibitors of type 4 dipeptidyl peptidase (DDP-4) were developed and approved for the oral treatment of type 2 diabetes. Its mode of action is to inhibit the degradation of incretins, such as type 1 glucagon like peptide (GLP-1), and GIP. GLP-1 stimulates glucose-dependent insulin secretion from pancreatic beta-cells and suppresses glucagon release from alpha-cells, thereby improving glucose control. Besides its action on the pancreas type 1 glucagon like peptide has direct effects on the heart, vessels and kidney mainly via the type 1 glucagon like peptide receptor (GLP-1R). Moreover, there are substrates of DPP-4 beyond incretins that have proven renal and cardiovascular effects such as BNP/ANP, NPY, PYY or SDF-1 alpha. Preclinical evidence suggests that DPP-4 inhibitors may be effective in acute and chronic renal failure as well as in cardiac diseases like myocardial infarction and heart failure. Interestingly, large cardiovascular meta-analyses of combined Phase II/III clinical trials with DPP-4 inhibitors point all in the same direction: a potential reduction of cardiovascular events in patients treated with these agents. A pooled analysis of pivotal Phase III, placebo-controlled, registration studies of linagliptin further showed a significant reduction of urinary albumin excretion after 24 weeks of treatment. The observation suggests direct renoprotective effects of DPP-4 inhibition that may go beyond its glucose-lowering potential. Type 4 dipeptidyl peptidase inhibitors have been shown to be very well tolerated in general, but for those excreted via the kidney dose adjustments according to renal function are needed to avoid side effects. In conclusion, the direct cardiac and renal effects seen in preclinical studies as well as meta-analysis of clinical trials may offer additional potentials - beyond improvement of glycemic control - for this newer class of drugs, such as acute kidney failure, chronic kidney failure as well as acute myocardial infarction and heart failure.
KW  - DDP-4 inhibition
KW  - Diabetes
KW  - GLP-1
KW  - Cardiovascular effects
KW  - Myocardial infarction
KW  - Kidney
KW  - Diabetic nephropathy
KW  - Acute renal failure
Y1  - 2012
U6  - https://doi.org/10.1159/000339028
SN  - 1420-4096
VL  - 36
IS  - 1
SP  - 65
EP  - 84
PB  - Karger
CY  - Basel
ER  -