( 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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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 ].

DPP-4 inhibitors and combined treatment in type 2 diabetes: The week duration of hyperglycemia in untreated diabetic rats resulted in decrease of GLP-1R staining [ 47 ]. The endpoint of the analysis was the percentage change in geometric mean of UACR after 24 weeks of treatment compared to baseline values. 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 ].

Albuminuria was also one of secondary endpoints in the study of Harashima et al. Clinicql De Mark The Journal of pharmacology and experimental…. whzt

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

In the exendin-4 study, glomerular macrophage infiltration was prevented by suppression of ICAM-1 production on glomerular endothelial cells and by inhibition of proinflammatory cytokine release from macrophages.

Combined treatment with linagliptin and diffeeentiators significantly reduced albuminuria compared with untreated diabetic mice, while monotherapy with either differentiatosr or linagliptin had no effect. Abstract 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.

GLP-1 receptor agonists vs.

We will discuss potential mechanism of these effects, the differences between various DPP-4 inhibitors, and future perspectives of its use in patients with diabetic kidney disease. Van Dijk et al. Teixeira De Lemos, H. View at Google Scholar L. Patient and treatment perspectives: In a recently published meta-analysis of 13 linagliptin trials including inhibitora focused on composite renal outcome, the hazard ratio of 0.


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 ].

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 ]. Glucagon like peptide-1 HMGB1: DPP-4 inhibitors for type 2 diabetes: To receive news and publication updates for International Journal of Endocrinology, enter your email address in the box below.

Toll-like receptor 2 TLR References Publications referenced by this paper. CKD stage 1 is characterized by normal GFR and urine findings mostly albuminuria or structural abnormalities of the kidney. 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.

Stages 2—5 are defined by specific values of GFR [ 7 ]. 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 ].

On the other hand, DPP-4 inhibitors have different pharmacokinetics, and their nonglucose lowering effects may vary in man due to different concentrations in various organs and due to distinct substrate selectivity of binding to DPP-4 enzyme [ 57 ].

In this insulinopenic model, vildagliptin increased GLP-1 levels but did not affect blood glucose levels [ 47 ].

Renal Effects of DPP-4 Inhibitors: A Focus on Microalbuminuria

As understanding of, and experience with, the growing number of DPP-4 inhibitors broadens, increasing evidence suggests that the class may offer advantages over other antidiabetic drugs in particular patient populations. The study with vildagliptin was performed on rats with streptozotocin-induced diabetes.


Many diabetic patients develop diabetic kidney disease despite intensive efforts to achieve optimal control of blood pressure and glycemia. Skip to search form Skip to main content. Additional important players contributing to kidney damage especially in patients with type 2 diabetes include arterial hypertension and dyslipidemia that commonly cluster with glucose wat disturbances in these patients [ 15 ]. The effect of linagliptin on the progression of nephropathy alone and in combination with the angiotensin receptor blocker telmisartan was tested.

Inhibitirs, pharmacodynamics and tolerability of multiple diffwrentiators doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients. This review offers an overview of DPP-4 inhibitors in T2DM and suggests some characteristics that may provide clinically relevant differentiators within this class.

View at Google Scholar G. Interestingly, the degree of microalbuminuria reduction did not correlate with the magnitude of change in HbA1c suggesting that the effects may have been independent of improvement in glycemic control. These results suggest that metformin does not share the albuminuria-lowering potential of thiazolidinediones and incretin-based therapies [ 60 ].

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Summary of Product Characteristics. The analysis included studies with both linagliptin monotherapy or add-on therapy to various glucose-lowering agents. Patients with diabetic kidney disease, even in stage 1, have a markedly increased clinicao of cardiovascular complications and hypoglycemia compared to patients without DKD [ 89 ]. The presence of microalbuminuria represents an important early sign of kidney damage in patients with diabetes [ 16 ].

Sitagliptin significantly lowered HbA1c and systolic and diastolic blood pressure.

Its levels correlate with the degree of mesangial expansion, interstitial fibrosis, and renal dysfunction, but not with the extent of microalbuminuria [ 25 ]. The total systemic glycocalyx volume is reduced by acute hyperglycemia in humans inhibitora 20 ].