( JUL 6) University of Rochester School of Medicine and Dentistry: DPP-4 inhibitors: what may be the clinical differentiators? Researchers detail in ‘DPP Clinical and experimental evidence with the DPP-4 inhibitors .. Gerich, J. () DPP-4 inhibitors: What may be the clinical differentiators?. (1) they were RCTs comparing DPP-4 inhibitors plus metformin as initial combination Gerich J. Dpp-4 inhibitors: what may be the clinical differentiators?.
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Associations between microalbuminuria, increased risk of cardiovascular complications, and progressive renal impairment are well described but the underlying pathophysiological mechanisms are only partially understood [ 16 ]. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes UKPDS DPP-4 inhibitors and combined treatment in type 2 diabetes: Predictors of medication nonadherence among patients with diabetes in Medicare Part D programs: R 3-amino-piperidinyl butynylmethyl 4-methyl-quinazolinylmethyl -3,7-dihydro-purine-2,6-dione BIa novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors.
View at Google Scholar H. Clinical Studies of Other Glucose Lowering Agents with Albuminuria Outcomes In general, all long-term studies with antidiabetic agents suggest that good glucose control can prevent or delay the development of microvascular complications in both type 1 and type 2 diabetes [ 1011 ].
Furthermore, two small studies with sitagliptin and the experimental studies described previously open the possibility that nephroprotection might be a class effect of DPP-4 inhibition. Diabetes was induced in endothelial nitric oxide synthase eNOS knockout mice which were used as an experimental model of nephropathy [ 48 ].
Upregulation of DPP-4 expression in renal glomeruli occurs during inflammation and usually accompanies the development of diabetes-induced glomerulosclerosis [ 6 ].
Advanced glycation end-products ARB: Nevertheless, larger trials designed primary on testing renal outcomes are necessary to confirm this interesting possibility. Several other DPP-4 inhibitors, including linagliptin and alogliptin, are currently in clinical development. Mechanism of Albuminuria The presence of microalbuminuria represents an important early sign of kidney damage in patients with diabetes [ 16 ].
According to current guidelines, the primary intervention in patients with detected albuminuria is the blockade of renin-angiotensin-aldosterone system RAAS with an angiotensin-converting enzyme inhibitor ACEi or angiotensin II receptor blocker ARB [ 52 ]. Light and electron microscopies of renal tissue revealed that vildagliptin treatment dose dependently inhibited interstitial expansion, glomerulosclerosis, and thickening of the glomerular basement membrane whar 47 ].
Proven additive effect of any antihyperglycemic agent on albuminuria lowering would be therefore of a high interest.
Podocyte loss is one of the first changes contributing to increased glomerular permeability for albumin. DPP-4 inhibitors for type 2 diabetes: Chronic kidney disease DKD: Patient and treatment perspectives: Toll-like receptor 2 TLR Glycemic inhjbitors with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: Stages 2—5 are defined by specific values of GFR [ 7 ]. Incretin-based therapies represent one of the most promising options in type 2 diabetes treatment owing to their good effectiveness with low risk of hypoglycemia and no weight gain.
Other numerous potential beneficial effects mmay incretin-based therapies have been suggested based mostly on experimental and small clinical studies including its beta-cell- and vasculoprotective actions and also numerous others pleiotropic positive effects such as neuroprotection and others [ 5 ]. Efficacy and safety of dipeptidyl peptidase-4 inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus: Albuminuria also positively correlates with markers of endothelial dysfunction and chronic low-grade inflammation including C-reactive protein [ 2829 ].
From This Paper Figures, tables, and topics from this paper. Its expression was decreased in diabetic compared with nondiabetic mice [ 32 ].
DPP-4 inhibitors: what may be the clinical differentiators?
View at Google Scholar E. This therapeutic diversity should help clinicians tailor treatment to the individual patient, thereby increasing the proportion that safely attain target HbA 1c levels, and reducing morbidity and mortality. One of the interesting possibilities that have emerged from experimental studies is the protective effect of DPP-4 inhibitors on the diabetic kidney disease [ 6 ].
The adverse effects of hyperglycemia are generally mediated through diverse metabolic pathways including increased reactive oxygen species formation, excessive production of advanced glycation end products AGEsand the activation of polyol, protein kinase C PKCand hexosamine pathways, respectively [ 12 ].
International Journal of Endocrinology
dppp In addition to pancreas, GLP-1 receptor GLP-1R is expressed in other numerous tissues including glomerular endothelial cells, mesangial cells, podocytes and also proximal tubular cells. Diabetic and controls rats were treated with sitagliptin or vehicle for 6 weeks. Both of these cytokines are upregulated in patients with type 2 diabetes [ 2627 ].
The differebtiators of microalbuminuria represents an important early sign of kidney damage in patients with diabetes [ 16 ]. Its levels correlate with the degree of mesangial expansion, interstitial fibrosis, and renal dysfunction, but not with the extent of microalbuminuria [ 25 ].
Streptozotocin-induced diabetes was used also in an experimental study with linagliptin [ 48 ].