( 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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The risk ratios for individual renal endpoints were 0. The expanding evidence base also suggests that certain differences between DPP-4 inhibitors may prove to be clinically significant. Anne L Peters Cleveland Clinic journal of medicine This decrease was prevented by treatment with vildagliptin.

DPP-4 inhibitors: what may be the clinical differentiators?

Endothelial glycocalyx forms a barrier to protein permeability in both systemic and glomerular capillaries. In addition to being a marker of renal damage, albuminuria has emerged as a predictive marker of increased risk of cardiovascular disease [ 51 ]. After 12 weeks of administration, linagliptin or telmisartan had no effect on glycemic control, while telmisartan reduced systolic blood pressure by 5.

Patients with diabetic kidney disease, even in stage 1, have a markedly increased risk of cardiovascular complications and hypoglycemia compared to patients without DKD [ 89 ].

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First study indicating possible beneficial effect of a DPP-4 inhibitor on the kidney in Man was a small observational study with sitagliptin [ 53 ]. Summary clinica Product Characteristics.

inhibitor Lobb Clinical therapeutics Microvesicle-bound DPP-4 secreted from tubular epithelial cells is found in urine and may be an early marker of renal damage before the onset of albuminuria [ 31 ]. Citations Publications citing this paper. In addition to experimental data for DPP-4 inhibitors, animal studies suggest inhibitord possible nephroprotective effects of GLP-1R agonists.


Onglyza saxagliptin 5 mg filmcoated tablets. Additional important differentiatorx contributing to kidney damage especially in patients with type 2 diabetes include arterial hypertension and dyslipidemia that commonly cluster with glucose metabolism disturbances in these patients [ 15 ].

Albuminuria also positively correlates with markers of endothelial dysfunction and chronic low-grade inflammation including C-reactive protein [ 2829 ]. Stephen Brunton International journal of clinical practice Advanced glycation end-products ARB: Ongoing studies, such as the MARLINA study comparing, prospectively, the effects of linagliptin to placebo on albuminuria may shed some light in this field [ 61 ].

Upregulation of DPP-4 expression in renal glomeruli occurs during inflammation and usually accompanies the development of diabetes-induced glomerulosclerosis [ 6 ]. DPP-4 inhibitors and combined treatment in type 2 diabetes: These therapeutics either increase concentrations of endogenous glucagon-like peptide-1 GLP-1 by the inhibition of its degradation dipeptidyl peptidase-4 inhibitors or directly stimulate GLP-1 receptor GLP-1 receptor agonists [ 4 ].

The study with sitagliptin administration assessed its effects on metabolic profile and renal lesions in a rat model of type 2 diabetic nephropathy [ 46 ]. Predictive factors of durability to sitagliptin: Furthermore, numerous ongoing long-term cardiovascular trials with DPP-4 inhibitors can bring novel crucial information about relationships among glucose control and macrovascular and microvascular complications and further elucidate the role of albuminuria in these processes.

Studies have shown that local changes in glomerular morphology and the extent of matrix accumulation in glomeruli and interstitium correlate with extent of albuminuria [ 19 ]. To receive news and publication updates for International Journal of Endocrinology, enter your email address in the box below.

The analysis included patients treated with linagliptin and 59 patients on placebo, respectively. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: Nevertheless, larger trials designed primary on testing renal outcomes are necessary to confirm this interesting possibility.

Since both micro- and macrovascular complications contribute in the increasing morbidity and mortality of patients with type 2 diabetes, novel antidiabetic therapies are intensively studied with respect to their possible beneficial effects on the long-term complications beyond their glucose-lowering properties [ 2 ]. The adverse effects of hyperglycemia are generally mediated cllinical 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 ].


DPP-4 inhibitors for type 2 diabetes: Clinifal of GLP-1R was demonstrated by immunohistochemical analysis in both glomeruli and tubules. Both exendin-4 [ 35 ] and liraglutide [ 50 ] ameliorated albuminuria decreased oxidative stress and inflammatory cytokines in a rat model of diabetic nephropathy. Clinical Studies of DPP-4 Inhibitors with Albuminuria Outcomes Many diabetic patients develop diabetic kidney disease despite intensive efforts to achieve optimal control of blood pressure and glycemia.

View at Google Scholar E. References Publications referenced by this paper.

DPP-4 inhibitors: what may be the clinical differentiators? – Semantic Scholar

Showing of 84 references. The endpoint of the analysis was the percentage change in geometric mean of UACR after 24 weeks of treatment compared to baseline values. In the exendin-4 study, glomerular macrophage infiltration was prevented inhibltors suppression of ICAM-1 production on glomerular endothelial cells and by inhibition of proinflammatory cytokine release from macrophages.

Diabetes was induced in endothelial nitric oxide synthase eNOS knockout mice which were used as an experimental model of nephropathy [ 48 ]. Preclinical Data of DPP-4 Inhibitors with Nephroprotective Outcomes Preclinical data suggesting nephroprotective effects of DPP-4 inhibitors are available for sitagliptin [ 46 ], vildagliptin [ 47 ], and linagliptin [ 48 ].

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.