Renoprotective Effects of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin: A Review in Type 2 Diabetes.

Existing Reviews

Please note, new claims can take a short while to show up.

No claims yet.

Annotation Summary

Term Occurence Count Dictionary
obesity 3 endocrinologydiseases
sitagliptin 52 endocrinologydiseasesdrugs
type 2 diabetes mellitus 1 endocrinologydiseases
diabetes mellitus 2 endocrinologydiseases
metabolic syndrome 1 endocrinologydiseases
metformin 4 endocrinologydiseasesdrugs

Graph of close proximity drug and disease terms (within 200 characters).

Note: If this graph is empty, then there are no terms that meet the proximity constraint.

Review

Having read the paper, please pick a pair of statements from the paper to indicate that a drug and disease are related.

Select Drug Character Offset Drug Term Instance
metformin 19121 either monotherapy, initial combination therapy (usually with a fixed dose combination of sitagliptin/ metformin ) or add-on therapy to metformin or to other antihyperglycaemic drugs, with or without metformin. Sitagliptin
metformin 19153 combination therapy (usually with a fixed dose combination of sitagliptin/metformin) or add-on therapy to metformin or to other antihyperglycaemic drugs, with or without metformin. Sitagliptin showed efficacy in decreasing
metformin 19217 sitagliptin/metformin) or add-on therapy to metformin or to other antihyperglycaemic drugs, with or without metformin . Sitagliptin showed efficacy in decreasing HbA1c, fasting plasma glucose (FPG), and postprandial plasma
metformin 34554 interaction between GLP-1 and the GLP-1R [[186]].Recently, in a study involving 164 DN patients treated with metformin , sitagliptin (100 mg, once a day) was able to decrease UAER, which presented a close correlation with
sitagliptin 1026 patients. It is also acknowledged as an independent risk factor for cardiovascular disease (CVD). Since sitagliptin was approved, many studies have been carried out revealing its ability to not only improve metabolic
sitagliptin 1953 review aims to provide an overview of the current knowledge in the field of renoprotective actions of sitagliptin , namely, improvement in diabetic dysmetabolism, hemodynamic factors, renal function, diabetic kidney
sitagliptin 6217 incretin-based therapies, which include glucagon-like peptide1 (GLP-1) agonists and DPP-4 inhibitors, of which sitagliptin was the first to be discovered and marketed [[29], [30]]. Moreover, these drugs may be used in various
sitagliptin 7574 need in diabetes by modulating glucose supply [[42], [43]]. In fact, DPP-4 inhibitors, and especially sitagliptin , have progressively increased their therapeutic prominence in the management of T2DM by their capability
sitagliptin 7783 capability to potentiate incretin activity. Various studies have described many pleiotropic effects of sitagliptin on various organs and tissues. The knowledge that DPP-4 has the highest expression levels in the kidneys
sitagliptin 7995 kidneys of mammals, which is additionally upregulated in DN [[44]], indicates that DPP-4 inhibition by sitagliptin is a plausible therapeutic target for management of diabetic nephropathy.This review outlines the evidence
sitagliptin 8179 nephropathy.This review outlines the evidence found in previous studies regarding the renoprotective action of sitagliptin in DN, focusing on renal function and lesions, as well as kidney tissue cytoprotective properties, particularly
sitagliptin 16792 fraction bound to plasma proteins of 38% [[79]]; its half-life is around 12.4 hours; hepatic metabolism of sitagliptin is minimal, mainly by cytochrome P450 3A4, while excretion occurs mainly (70–80%) by the kidney in
sitagliptin 17029 a renal clearance of approximately 350 ml/min [[80]]. In general, the pharmacokinetic profile of sitagliptin is similar in both healthy volunteers and T2DM patients. The pharmacokinetic properties of the drug
sitagliptin 18941 diabetes treatment and is orally active [[95], [96]].Clinical trials have demonstrated the efficacy of sitagliptin in terms of improving glycaemic control in T2DM patients, used as either monotherapy, initial combination
sitagliptin 19109 patients, used as either monotherapy, initial combination therapy (usually with a fixed dose combination of sitagliptin /metformin) or add-on therapy to metformin or to other antihyperglycaemic drugs, with or without metformin.
sitagliptin 19641 Targeted by DiabetesExperimental studies performed in animal models of T2DM that were treated with sitagliptin showed remarkable beneficial effects on glucose and HbA1c levels, an improvement of insulin resistance,
sitagliptin 19857 together with promotion of weight loss and amelioration of lipid profile [[101]–[110]]. Moreover, sitagliptin was able to consistently alleviate oxidative stress and inflammation, which are key players in diabetes
sitagliptin 20592 oxidative stress, inflammation, and apoptosis [[19], [78], [103], [112]–[118]]. Concerning the impact of sitagliptin on lipid profiles in T2DM patients, the majority of studies reported a beneficial effect on triglycerides
sitagliptin 20995 diabetic patients, in both a GLP-1-dependent and GLP-1-independent manner [[121], [122]]. Furthermore, sitagliptin was able to increase EPC levels in diabetic patients [[78]].Our research group has extensively studied
sitagliptin 21136 levels in diabetic patients [[78]].Our research group has extensively studied the protective effects of sitagliptin on various organs targeted by diabetes, namely, the pancreas, retina, and kidney, in an animal model
sitagliptin 21552 decreased insulin resistance and pro-proliferative and angiogenic actions [[103], [123]]. In the retina, sitagliptin treatment prevented changes in the endothelial subcellular distribution of tight junction proteins and
sitagliptin 21794 and inflammatory and apoptotic states [[124]]. Later studies in type 1 diabetic rats revealed that sitagliptin could prevent the increase in blood-retinal barrier permeability and decrease the retinal inflammation
sitagliptin 22318 [[132]–[134]].Besides decreasing insulin resistance [[5], [135], [136]] and improving hepatic insulin sensitivity, sitagliptin seems also to prevent steatosis [[137]] through GLP-1R signalling in the liver and reduction of endoplasmic
sitagliptin 22776 cells by DPP-4 inhibition have also been identified [[140]].Treatment of nonobese diabetic mice with sitagliptin not only prevented linoleic acid-induced adipose tissue hypertrophy but also protected against adipose
sitagliptin 22969 protected against adipose tissue inflammation [[129], [137]].In T2DM rats with uncontrolled neuropathy, sitagliptin as add-on to insulin therapy produced neuroprotective effects and ameliorated hyperalgesia, oxidative
sitagliptin 23266 Affords Renoprotection in Diabetic Nephropathy4.1. Effects of Sitagliptin on Renal FunctionThe effects of sitagliptin on DN, using the ZDF rat, noticeably reduced renal dysfunction and injury in this model. In fact, sitagliptin
sitagliptin 23376 sitagliptin on DN, using the ZDF rat, noticeably reduced renal dysfunction and injury in this model. In fact, sitagliptin treatment was able to decrease blood urea nitrogen (BUN) levels to values identical to those observed
sitagliptin 24238 proximal renal tubules, which play a role in regulating the composition of urine. DPP-4 inhibition by sitagliptin administration increases GLP-1 availability which stimulates GLP-1R in blood vessels, through the sequential
sitagliptin 26603 renoprotection in the setting of hypertension and other disorders of sodium retention. However, in the case of sitagliptin , available data is not yet sufficient to confirm this protective effect [[74], [76]].4.2. Effects of
sitagliptin 29620 able to improve renal lesions in experimental animal models. In fact, in the obese diabetic ZDF rat, sitagliptin treatment ameliorated glomerular, tubulointerstitial (Figure 1(b)), and vascular lesions (Figure 2(b))
sitagliptin 30527 various organs and tissues, including the kidney [[101]–[103], [138], [171], [172]].Considering that sitagliptin is not able to completely normalize hyperglycaemia in studies using low doses [[8], [103], [126]], an
sitagliptin 32598 permeability, oxidative stress, renal hypertrophy, and tubulointerstitial lesions. DPP-4 inhibition by low-dose sitagliptin has prevented the inflammatory profile and the proapoptotic state observed in the diabetic rat kidney,
sitagliptin 32853 renal function and tissular lesions (glomerular, tubulointerstitial, and vascular lesions). In fact, sitagliptin was able to prevent the increase in both mRNA and protein levels of the proinflammatory cytokines IL-1β
sitagliptin 33069 and TNF-α in the diabetic kidneys of ZDF rats [[8]].In Wistar rats treated with low- or high-dose sitagliptin during 16 weeks, urinary albumin excretion rate (UAER), serum creatinine, and kidney hypertrophy were
sitagliptin 33329 clearance rate and active GLP-1 levels were increased, with more pronounced changes in the high-dose sitagliptin -treated animals. Glomerular lesions were also improved following sitagliptin treatment. Protein and
sitagliptin 33406 changes in the high-dose sitagliptin-treated animals. Glomerular lesions were also improved following sitagliptin treatment. Protein and mRNA expression levels of podocalyxin and GLP-1R were significantly increased
sitagliptin 34058 albuminuria [[64], [184]]. These overall results also confirm a delay in DN progression promoted by sitagliptin , possibly via the inhibition of ERK1/2 signalling which seems to be activated by AGEs and is implicated
sitagliptin 34565 GLP-1 and the GLP-1R [[186]].Recently, in a study involving 164 DN patients treated with metformin, sitagliptin (100 mg, once a day) was able to decrease UAER, which presented a close correlation with markers of
sitagliptin 35238 expression in mesangial cells [[189]]. Li et al. [[190]] suggest that the renoprotective mechanism of sitagliptin may be due to a reduction in protein kinase B (PKB)/Akt levels, which are involved in apoptosis pathways
sitagliptin 36216 TUNEL-positive cells induced by chronic hyperglycaemia in the kidneys of this animal model [[8]]. In addition, sitagliptin was able to ameliorate serum TG content, thus reducing lipotoxicity-evoked apoptosis in the kidney [[8],
sitagliptin 36584 in vivo, leading to DN [[49], [56], [194]]. Therefore, the reduction of oxidative stress afforded by sitagliptin could eventually reduce ROS production and the consequent risk of cell death. A study on renal ischemia
sitagliptin 36742 consequent risk of cell death. A study on renal ischemia reperfusion damage in diabetic rats found sitagliptin to significantly decrease lipid peroxidation, xanthine oxidase activity, myeloperoxidase activity, and
sitagliptin 37064 glutathione, glutathione peroxidase, superoxide dismutase, and catalase were significantly increased in sitagliptin -treated diabetic rats compared to those in the nontreated ones [[195]]. Other studies have demonstrated
sitagliptin 37409 and apoptosis [[196]–[199]].5. Concluding RemarksThe innovative class of DPP-4 inhibitors, such as sitagliptin , seem to address previously unmet needs in diabetes. In fact, DPP-4 has the highest expression levels
sitagliptin 37645 mammals, which is additionally upregulated in diabetic-induced CKD, indicating that DPP-4 inhibition by sitagliptin is a plausible therapeutic target for management of DN. In fact, several studies have been describing
sitagliptin 37791 for management of DN. In fact, several studies have been describing putative pleiotropic effects of sitagliptin on various organs and tissues. Sitagliptin showed not only the capacity to ameliorate diabetic dysmetabolism
sitagliptin 38144 these effects suggest a role in prevention of T2DM evolution and its complications. In the kidney, sitagliptin seems to provide renoprotection by restoring GLP-1 diuretic and natriuretic actions and by other mechanisms,
sitagliptin 38406 anti-inflammatory, and antioxidant effects. However, additional studies are needed to clarify whether sitagliptin acts through indirect action via insulin secretion increment or through direct tissular DPP-4 inhibition.
sitagliptin 38875 substrates).Due to its unique mechanism of action and pharmacological properties, DPP-4 inhibitors (including sitagliptin ) have conquered their place in T2DM management. In addition, the low potential for interactions with
sitagliptin 39613 Disclosure of its protective actions on the diabetic kidney could open up the possibility of using sitagliptin therapy as a renoprotective strategy against the development and/or delay of DN.Figure 1Effects of sitagliptin
sitagliptin 39724 therapy as a renoprotective strategy against the development and/or delay of DN.Figure 1Effects of sitagliptin treatment on diabetic nephropathy lesions in an experimental model of type 2 diabetes. (a) Histopathological
sitagliptin 40530 diabetic untreated ZDF rat (original magnification ×100). (b) Improvement of histopathological lesions in sitagliptin -treated diabetic nephropathy. Glomerular lesions: Reduction of lesion severity, with global rise in
sitagliptin 40982 interstitial fibrosis and tubular atrophy (IFTA); PAS staining of a kidney section from an obese diabetic sitagliptin -treated ZDF rat (original magnification ×100).Figure 2Effects of sitagliptin treatment on diabetic
sitagliptin 41060 from an obese diabetic sitagliptin-treated ZDF rat (original magnification ×100).Figure 2Effects of sitagliptin treatment on diabetic nephropathy vascular lesions in an experimental model of type 2 diabetes. (a)
sitagliptin 41558 untreated ZDF rat (original magnification ×400). (b) Improvement of histopathological vascular lesions in sitagliptin -treated diabetic nephropathy: A marked reduction in total wall and intimal layer thickening, showing
sitagliptin 41753 thickening, showing normal endothelial cells; PAS staining of a kidney section from an obese diabetic sitagliptin -treated ZDF rat (original magnification ×400)
Select Disease Character Offset Disease Term Instance
diabetes mellitus 1631 for developing micro- and macrovascular complications. Currently, it is becoming clearer that type 2 diabetes mellitus (T2DM) management must envision not only the improvement in glycaemic control but also, and particularly,
diabetes mellitus 2127 factors, renal function, diabetic kidney lesions, and cytoprotective properties.1. IntroductionType 2 diabetes mellitus (T2DM) is recognized as being a group of chronic diseases characterized by hyperglycaemia where the
metabolic syndrome 12895 appears to support not only the aggravation of CKD but also the development of CVD called the cardiorenal metabolic syndrome [[69]]. However, the underlying mechanisms of micro- and macrovascular complications of diabetes are
obesity 10237 overactivity of the RAAS and promotion of VEGF deficiency. Interaction of metabolic factors, such as obesity and chronic hyperglycaemia, alters vasoactive regulating mechanisms of afferent and efferent arteriolar
obesity 12693 eventually become irreversible [[64]–[68]].The cumulative presence of cooperative risk factors, namely, obesity , hypertension, insulin resistance, hyperglycaemia, dyslipidaemia, and microalbuminuria, appears to support
obesity 25462 surface expression and/or activity [[148]]. Furthermore, DPP-4 inhibition, in experimental models of obesity and heart failure, was able to upregulate megalin, a receptor that mediates endocytosis of proteins
type 2 diabetes mellitus 1624 risk for developing micro- and macrovascular complications. Currently, it is becoming clearer that type 2 diabetes mellitus (T2DM) management must envision not only the improvement in glycaemic control but also, and particularly,

You must be authorized to submit a review.