( 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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Non-insulin dependent diabetes mellitus: Conclusion and Perspectives The results of published preclinical and clinical studies suggest that DPP-4 inhibitors may have a potential to lower albuminuria and to also possess other more complex nephroprotective properties. Other numerous potential beneficial effects of incretin-based therapies have been suggested based mostly on experimental and small clinical studies including its beta-cell- and vasculo-protective actions. Many diabetic patients develop diabetic kidney disease despite intensive efforts to achieve optimal control of blood pressure and glycemia.

After 6 months of sitagliptin treatment, albuminuria measured by urinary albumin creatinine ratio UACR significantly decreased both in the patients with relatively modest microalbuminuria and the patients with more pronounced microalbuminuria at baseline.

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 ]. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: 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

Summary of Product Characteristics. Ina comprehensive analysis of randomized, double-blind, placebo-controlled trials duration 24—52 weeks with linagliptin was published [ 55 ].

Intercellular adhesion molecule-1 GLP-1R: In a recently published meta-analysis of 13 linagliptin trials including patients focused on composite renal outcome, the hazard ratio of 0. 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. View at Google Scholar H.

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Numerous studies have shown that the risk of diabetic kidney disease is tightly linked to poor glucose control in both type 1 and type 2 diabetes clinnical 1011 ]. Van De Mark The Journal of pharmacology and experimental…. Here, we review the renal effects of DPP-4 inhibitors with special focus on its influence on the onset and progression of microalbuminuria, as presence of microalbuminuria represents an important early sign of inihbitors damage and is also associated with increased risk of hypoglycemia and cardiovascular complications.


Sitagliptin treatment of diabetic rats lowered glycemia and ameliorated glomerular, tubulointerstitial, and vascular lesions. Preclinical data suggesting nephroprotective effects ditferentiators DPP-4 inhibitors are available for sitagliptin [ 46 ], vildagliptin [ 47 ], and linagliptin [ 48 ].

First study indicating possible beneficial effect of a DPP-4 inhibirors on the kidney in Man was a small observational study with sitagliptin [ 53 ]. Nevertheless, their exact role and dlinical in renoprotective effects of DPP-4 inhibitors has not yet been tested [ 38 ].

One of the recently emerged interesting features of dipeptidyl peptidase-4 DPP-4 inhibitors is its possible protective effect on the diabetic kidney disease. Currently, three DPP-4 inhibitors – sitagliptin, vildagliptin and saxagliptin – have been approved in various countries worldwide. To receive news and publication updates for International Journal of Endocrinology, enter your email address in the box below.

View at Google Scholar A.

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

Van Dijk et al. 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 ]. DPP-4 inhibitors for type 2 diabetes: CKD stage 1 is characterized by normal GFR and urine findings mostly albuminuria or structural abnormalities of the kidney. Activation of these pathways leads to a complex dysregulation of various effector molecules resulting in cellular damage and dysfunction [ 12 ].

The results of published preclinical and clinical studies suggest that DPP-4 inhibitors may have a potential to lower albuminuria and to also possess other more complex nephroprotective properties.

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 ]. The total systemic glycocalyx volume is reduced by acute hyperglycemia in humans [ 20 ].

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

These data suggest that the nephroprotection by Differetniators inhibition was mediated by antiapoptotic, anti-inflammatory, and antioxidative changes. View at Google Scholar K. Mechanism of Albuminuria The presence of microalbuminuria represents an important early sign of kidney damage in patients br diabetes [ 16 ]. 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 ].

Teixeira De Lemos, H.


Endothelial nitric oxide synthase GFR: 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 differentiatogs the role of albuminuria in these processes. Aravindababu European Journal of Clinical Pharmacology DPP-4 inhibitors are known to exert also GLP-1 independent effects as DPP-4 cleaves a wide range of other substrates such as neuropeptides, hormones, cytokines, and chemokines [ 630 ].

After 52 weeks sitagliptin treatment reduced HbA1c by 0. Stimulation of GLP-1 receptor in turn increases insulin secretion and suppresses excessive glucagon release leading to improved glucose inibitors. We performed a primary Medline search using combinations of keywords: According to current guidelines, the primary intervention in patients with detected albuminuria is the blockade of renin-angiotensin-aldosterone inhiitors RAAS with an angiotensin-converting enzyme inhibitor ACEi or angiotensin II receptor blocker ARB [ 52 ].

Expression of GLP-1R was demonstrated by immunohistochemical analysis in both glomeruli and tubules. Attenuation of the prandial incretin effect, mediated by glucagon-like peptide-1 GLP-1 and glucose-dependent insulinotropic peptide Whaatcontributes to hyperglycemia in type 2 diabetes mellitus T2DM. From This Paper Figures, tables, and topics from this paper.

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 inbibitors their possible beneficial effects on the long-term complications beyond their glucose-lowering properties [ 2 ]. Since the launch of sitagliptin ina compelling body of evidence has accumulated showing that dipeptidyl peptidase-4 DPP-4 inhibitors, which augment endogenous GLP-1 hwat GIP levels, represent an important advance in the management of T2DM.

Increasing prevalence of diabetes worldwide, leading to a steep rise of patients with chronic complications, represents one of the major health problems of the current medicine [ 1 ]. Both exendin-4 [ 35 ] and liraglutide [ 50 ] ameliorated albuminuria decreased oxidative stress and inflammatory cytokines in a rat model of diabetic nephropathy. 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 ].

Experimental studies have shown that some of these pathophysiological mechanisms are potentially modifiable by DPP-4 inhibition [ 6 ]. The analysis included studies with both linagliptin monotherapy or add-on therapy to various glucose-lowering agents.