scholarly journals Urate-lowering effects of dipeptidyl peptidase-4 inhibitors

2020 ◽  
Vol 23 (4) ◽  
pp. 349-356
Author(s):  
Taras S. Panevin ◽  
Olga V. Zhelyabina ◽  
Maxim S. Eliseev ◽  
Marina V. Shestakova
Keyword(s):  
Extracellular Fluid ◽  
Dipeptidyl Peptidase ◽  
Serum Glucose ◽  
Dipeptidyl Peptidase 4 ◽  
Glucose Levels ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Treatment Of Diabetes ◽  
Positive Effect ◽  
Metabolic Syndrome Components

Hyperuricemia is an increase of uric acid (UA) concentration in blood serum >420 pmol/L in men or >360 pmol/L in women and is considered to be a common biochemical abnormality. This condition shows that the extracellular fluid is oversaturated with urates, which concentration exceeds the limit of their solubility. This fact predisposes to the formation of crystals of sodium salt of UA and results in gout, urolithiasis, and other diseases. The frequent combination and relationship between purine and carbohydrate metabolism were noted in previous studies. In this regard, the choice of drugs for correcting these disorders should consider the possibility of a combined positive effect on the UA and serum glucose levels. The hypoglycemic drugs with pleiotropic effects on several metabolic syndrome components are considered to be of particular interest. Currently, one of the most frequently prescribed groups of drugs in the treatment of diabetes mellitus type 2 are dipeptidyl peptidase-4 inhibitors, which affect the level of incretins (gliptins). These drugs can be potentially attractive in patients with purine metabolism disorders since the available data indicate that these drugs affect UA level.

scholarly journals The association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors: a ten-year prospective observational study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Vaia Lambadiari ◽  
Aikaterini Kountouri ◽  
Foteini Kousathana ◽  
Emmanouil Korakas ◽  
Georgios Kokkalis ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Prospective Observational Study ◽  
Dipeptidyl Peptidase ◽  
Dermatology Department ◽  
Steroid Administration ◽  
Dipeptidyl Peptidase 4 ◽  
Increased Risk ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
A Prospective Study

Abstract Background Bullous pemphigoid is the most common bullous chronic autoimmune skin disease. Recent studies have suggested dipeptidyl-peptidase 4 inhibitors as possible predisposing agents of bullous pemphigoid. The objective of our study was to prospectively estimate the association between gliptins and the development of bullous pemphigoid. Methods We conducted a prospective study which included all patients diagnosed with biopsy-proven bullous pemphigoid in the Dermatology Department of our hospital between April 1, 2009 and December 31,2019. The diagnosis of bullous pemphigoid was based on specific clinical, histological and immunological features. Results Overall 113 consecutive patients (age 75 ± 13 years, 62 females) with the diagnosis of bullous pemphigoid were enrolled. Seventy-six patients (67.3%) suffered from type 2 Diabetes and 52 (46%) were treated with dipeptidyl-peptidase 4 inhibitors. The most frequent prescribed gliptin was vildagliptin, being administered to 45 cases (39.8% of total patients enrolled, 86.5% of the patients treated with gliptins). Gliptins were withdrawn immediately after the diagnosis of bullous pemphigoid, which together with steroid administration led to remission of the rash. Conclusions This study revealed that treatment with dipeptidyl-peptidase 4 inhibitors, especially vildagliptin, is significantly associated with an increased risk of bullous pemphigoid development.

scholarly journals Dipeptidyl peptidase-4 inhibitors do not increase the risk of cardiovascular events in type 2 diabetes: a cohort study

2014 ◽  
Vol 51 (6) ◽  
pp. 1015-1023 ◽  
Author(s):  
Seoyoung C. Kim ◽  
Robert J. Glynn ◽  
Jun Liu ◽  
Brendan M. Everett ◽  
Allison B. Goldfine
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Cardiovascular Events ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors

scholarly journals The role of renal dipeptidyl peptidase-4 in kidney disease: renal effects of dipeptidyl peptidase-4 inhibitors with a focus on linagliptin

2018 ◽  
Vol 132 (4) ◽  
pp. 489-507 ◽  
Author(s):  
Keizo Kanasaki
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Kidney Disease ◽  
Dipeptidyl Peptidase ◽  
Renal Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Membrane Bound

Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes may have nephroprotective effects beyond the reduced renal risk conferred by glycemic control. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. The kidneys contain the highest levels of DPP-4, which is increased in diabetic nephropathy. DPP-4 inhibitors are a chemically heterogeneous class of drugs with important pharmacological differences. Of the globally marketed DPP-4 inhibitors, linagliptin is of particular interest for diabetic nephropathy as it is the only compound that is not predominantly excreted in the urine. Linagliptin is also the most potent DPP-4 inhibitor, has the highest affinity for this protein, and has the largest volume of distribution; these properties allow linagliptin to penetrate kidney tissue and tightly bind resident DPP-4. In animal models of kidney disease, linagliptin elicited multiple renoprotective effects, including reducing albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis, independent of changes in glucagon-like peptide-1 (GLP-1) and glucose levels. At the molecular level, linagliptin prevented the pro-fibrotic endothelial-to-mesenchymal transition by disrupting the interaction between membrane-bound DPP-4 and integrin β1 that enhances signaling by transforming growth factor-β1 and vascular endothelial growth factor receptor-1. Linagliptin also increased stromal cell derived factor-1 levels, ameliorated endothelial dysfunction, and displayed unique antioxidant effects. Although the nephroprotective effects of linagliptin are yet to be translated to the clinical setting, the ongoing Cardiovascular and Renal Microvascular Outcome Study with Linagliptin in Patients with Type 2 Diabetes Mellitus (CARMELINA®) study will definitively assess the renal effects of this DPP-4 inhibitor. CARMELINA® is the only clinical trial of a DPP-4 inhibitor powered to evaluate kidney outcomes.

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