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renal sitagliptin

Smeeta Sadar, Dipti Kaspate, Neeraj Vyawahare
Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. L-Glutamine (LG) is naturally occurring amino acids with antidiabetic and antioxidant potential. The aim of present investigation was to evaluate the potential of LG against streptozotocin (STZ)-induced diabetic nephropathy (DN) in laboratory rats. DN was induced in male Wistar rats (200-220 g) by intraperitoneal administration of STZ (55 mg/kg). Animals were treated orally with either distilled water (10 mg/kg) or LG (250, 500, and 1000 mg/kg) or Sitagliptin (5 mg/kg)...
October 19, 2016: Renal Failure
M B Rehman, B V Tudrej, J Soustre, M Buisson, P Archambault, D Pouchain, H Vaillant-Roussel, F Gueyffier, J-L Faillie, M-C Perault-Pochat, C Cornu, R Boussageon
BACKGROUND: Guidelines for type 2 diabetes (T2D) recommend reducing HbA1c through lifestyle interventions and glucose-lowering drugs (metformin, then combination with dipeptidyl peptidase-4 inhibitors [DPP-4Is] among other glucose-lowering drugs). However, no double-blind randomized clinical trial (RCT) compared with placebo has so far demonstrated that DDP-4Is reduce micro- and macrovascular complications in T2D. Moreover, the safety of DPP-4Is (with increased heart failure and acute pancreatitis) remains controversial...
October 10, 2016: Diabetes & Metabolism
Lennart Tonneijck, Mark M Smits, Marcel H A Muskiet, Trynke Hoekstra, Mark H H Kramer, A H Jan Danser, Piet M Ter Wee, Michaela Diamant, Jaap A Joles, Daniël H van Raalte
OBJECTIVE: To investigate effects of dipeptidyl peptidase-4 inhibitor (DPP-4I) sitagliptin or glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide treatment on renal hemodynamics, tubular functions, and markers of renal damage in overweight patients with type 2 diabetes without chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: In this 12-week, randomized, double-blind trial, 55 insulin-naïve patients with type 2 diabetes (mean ± SEM: age 63 ± 7 years, BMI 31...
September 1, 2016: Diabetes Care
Devada Singh-Franco, Catherine Harrington, Eglis Tellez-Corrales
OBJECTIVE: This updated meta-analysis determines the effect of dipeptidyl peptidase-4 inhibitors on glycemic and tolerability outcomes in patients with type 2 diabetes mellitus and chronic kidney disease with glomerular filtration rate of ⩽60 mL/min or on dialysis. METHODS: In all, 14 citations were identified from multiple databases. Qualitative assessments and quantitative analyses were performed. RESULTS: There were 2261 participants, 49-79 years of age, 49% men and 44% Caucasians...
2016: SAGE Open Medicine
Se Hee Park, Joo Young Nam, Eugene Han, Yong-Ho Lee, Byung-Wan Lee, Beom Seok Kim, Bong-Soo Cha, Chul Sik Kim, Eun Seok Kang
Hyperglycemia is associated with increased mortality and morbidity in patients with type 2 diabetes mellitus (T2DM) who are undergoing dialysis. Although dipeptidyl peptidase-4 (DPP-4) inhibitors have been widely used in end-stage renal disease (ESRD) patients with T2DM, there are few studies on their efficacy in this population. We studied the effect of 3 different DPP-4 inhibitors on metabolic parameters in ESRD patients with T2DM.Two hundred ESRD patients with T2DM who were treated with DPP-4 inhibitors (sitagliptin, vildagliptin, or linagliptin) were enrolled and analyzed retrospectively...
August 2016: Medicine (Baltimore)
Merlin C Thomas, Päivi M Paldánius, Rajeev Ayyagari, Siew Hwa Ong, Per-Henrik Groop
INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the management of patients with type 2 diabetes mellitus (T2DM) and renal impairment (RI). A systematic literature review was performed to compare the efficacy and safety of DPP-4 inhibitors in patients with T2DM and RI. METHODS: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials (cut-off, June 2015) to identify ≥12-week, randomized, placebo-controlled trials on DPP-4 inhibitors in ≥50 patients with T2DM and RI...
September 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Abigail Tebboth, Sally Lee, Anna Scowcroft, Paula Bingham-Gardiner, Will Spencer, John Bolodeoku, Syed Wasi Hassan
PURPOSE: The majority of people with type 2 diabetes mellitus (T2DM) will develop chronic kidney disease in their lifetime. Because most dipeptidyl peptidase (DPP)-4 inhibitors require dose adjustment in patients with T2DM and renal impairment, we aimed to understand how these treatments are prescribed in UK clinical practice, and to determine whether recommended dose adjustments are being made at initial prescription. METHODS: This retrospective, descriptive cohort study analyzed data from the Clinical Practice Research Datalink (CPRD)...
August 2016: Clinical Therapeutics
Yi-Chih Hung, Che-Chen Lin, Wei-Lun Huang, Man-Ping Chang, Ching-Chu Chen
The incidence of heart failure hospitalization (HHF) after taking sitagliptin in type 2 diabetes (T2DM) patients with end stage renal disease (ESRD) on dialysis is unclear. In this population-based cohort study, we identified individuals with T2DM and ESRD on dialysis who were treated with sitagliptin between 2009 and 2011 and randomly selected a control cohort matched by age, sex, duration of T2DM, hypertension medications, use of statin and aspirin, sulfonylureas, glinides, and insulin usage, atherosclerotic heart disease, congestive heart failure and chronic obstructive pulmonary disease at a 1:4 ratio...
2016: Scientific Reports
Xia Chen, Qian Zhao, Jianyan Zhang, Tao Liu, Ji Jiang, Pei Hu
AIM: This study investigated the pharmacokinetics of sitagliptin and metformin after multiple oral doses of the sitagliptin/metformin fixed-dose combination (MK0431A) tablet in healthy Chinese volunteers. METHODS: This was a singlecenter, randomized study in 24 healthy adults. Subjects received twice-daily doses of MK0431A 50-mg/500-mg tablet and 50-mg/850-mg tablet for 7 days. Serial blood and urine samples were collected at predefined time points for bioassay of sitagliptin and metformin...
September 2016: International Journal of Clinical Pharmacology and Therapeutics
Shouhei Yuasa, Kazuyoshi Sato, Masahiko Takai, Masashi Ishikawa, Shinichi Umezawa, Akira Kubota, Hajime Maeda, Akira Kanamori, Masaaki Miyakawa, Yasushi Tanaka, Yasuo Terauchi, Ikuro Matsuba
BACKGROUND: Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is an effective oral antidiabetic agent as both monotherapy and when combined with insulin. Data from three observational studies performed in patients with type 2 diabetes receiving sitagliptin therapy in the routine clinical setting were integrated to conduct factor analysis of the changes in hemoglobin A1c (HbA1c), body weight, and estimated glomerular filtration rate (eGFR) over 12 months. METHODS: Among patients with type 2 diabetes attending medical institutions affiliated with Kanagawa Physicians Association, those using sitagliptin were followed for 1 year...
June 2016: Journal of Clinical Medicine Research
Guntram Schernthaner, Marie Helene Schernthaner-Reiter, Gerit-Holger Schernthaner
During the last decade, the armamentarium for glucose-lowering drugs has increased enormously by the development of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors, allowing individualization of antidiabetic therapy for patients with type 2 diabetes (T2DM). Some combinations can now be used without an increased risk for severe hypoglycemia and weight gain. Following a request of the US Food and Drug Administration, many large cardiovascular (CV) outcome studies have been performed in patients with longstanding disease and established CV disease...
June 2016: Clinical Therapeutics
Masaaki Sagara, Kunihiro Suzuki, Chie Aoki, Seiichi Tanaka, Isao Taguchi, Teruo Inoue, Yoshimasa Aso
BACKGROUND: The aim of the present study was to elucidate the effect of teneligliptin on oxidative stress and endothelial function in Japanese patients with type 2 diabetes and chronic kidney disease (CKD). METHODS: Forty-five patients with type 2 diabetes and CKD who received sitagliptin for at least 12 months were randomized to either continue sitagliptin (n = 23) or switch to teneligliptin (n = 22) for 24 weeks. The following parameters were evaluated at baseline and after 24 weeks of treatment with continued sitagliptin or teneligliptin: blood pressure, haemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), urinary albumin excretion, endothelial function by reactive hyperaemia index (RHI; EndoPAT(®) system), reactive oxygen metabolites (ROMs) measured by the d-ROMS test, 8-hydroxy-2'-deoxyguanosine, urinary liver-type fatty acid binding protein (L-FABP), and urinary 8-isoprostane...
2016: Cardiovascular Diabetology
G Penno, M Garofolo, S Del Prato
AIMS: Type 2 diabetes mellitus (T2DM) is associated with a high risk of chronic kidney disease (CKD). About 20% of patients with T2DM have CKD of stage ≥ 3; up to 40% have some degree of CKD. Beyond targeting all renal risk factors together, renin-angiotensin-aldosterone system blockers are to date the only effective mainstay for the treatment of diabetic kidney disease (DKD). Indeed, several potentially nephroprotective agents have been in use, which have been unsuccessful. Some glucose-lowering agents, including dipeptidyl peptidase-4 inhibitors (DPP-4i), have shown promising results...
May 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Samia M Ali, Hoda Khalifa, Dalia K Mostafa, Amal El Sharkawy
AIM: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, and thus, the ability of antidiabetic drugs to ameliorate renal microvascular disease may be as important as their ability to control blood glucose. Therefore, we investigated the reno-protective effect of the antidiabetic drugs, Sitagliptin and Pioglitazone, versus combined Metformin/Enalapril in a rat model of type 2 diabetes. METHOD: Male Wistar rats were randomly assigned to be either normal control or diabetic...
May 15, 2016: Life Sciences
Teresa Vanessa Fiorentino, Giorgio Sesti
Clinical trials of glucose-lowering strategies in patients with type 2 diabetes mellitus (T2DM) have shown a favorable effect of intensive glycemic control on microvascular complications but failed to show a clear benefit on cardiovascular events. In 2008, the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have required stringent criteria to approve new glucose-lowering drugs, demanding proof of cardiovascular safety. As a result of these regulatory requirements, a number of cardiovascular outcome trials in T2DM have been conducted examining the cardiovascular safety of novel glucose-lowering drugs...
March 2016: Giornale Italiano di Cardiologia
Sally A Abuelezz, Nevien Hendawy, Sara Abdel Gawad
OBJECTIVE: This study aimed to investigate the potential protective effect of sitagliptin on gentamicin-induced nephrotoxicity and to elucidate the underlying mechanism. METHODS: Wistar rats were allocated as follows: Gentamicin group: received gentamicin intraperitoneally (100 mg/kg/day); Gentamicin plus sitagliptin group: received simultaneous gentamicin and sitagliptin (30 mg/kg/day orally); Sitagliptin group: received only sitagliptin; and CONTROL GROUP: received saline...
April 2016: Journal of Pharmacy and Pharmacology
Wenqi Li, Meiping Guan, Zongji Zheng, Yaoming Xue
OBJECTIVE: To investigate the effects of the DPP4 inhibitor sitagliptin on the expressions of early growth response-1 (Egr-1) and fibronectin in the kidney of ApoE gene knockout mice. METHODS: Eight-week-old male ApoE gene knockout mice were randomly divided into sitagliptin + apoE(-/-) group and apoE(-/-) group (n=6), with 6 C57BL mice as the normal control group. After feeding with high-fat diet and drug treatment for 16 weeks, the mice underwent intraperitoneal glucose tolerance test (IPGTT) and were measured for 24-h urinary albumin using ELISA...
January 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Yuki Tanaka, Shinji Kume, Masami Chin-Kanasaki, Hisazumi Araki, Shin-ichi Araki, Satoshi Ugi, Takeshi Sugaya, Takashi Uzu, Hiroshi Maegawa
Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells...
February 12, 2016: Biochemical and Biophysical Research Communications
Jaehyun Bae, Min Jung Lee, Eun Yeong Choe, Chang Hee Jung, Hye Jin Wang, Myoung Soo Kim, Yu Seun Kim, Joong Yeol Park, Eun Seok Kang
BACKGROUND: The use of dipeptidyl peptidase-4 (DPP-4) inhibitors is increasing among renal transplant patients with diabetes. However, the glucose-lowering efficacies of various DPP-4 inhibitors and their effects on blood cyclosporine levels have not been fully investigated. We compared the glucose-lowering efficacies of DPP 4 inhibitors and evaluate their effects on the blood levels of cyclosporine in renal transplant recipients with diabetes. METHODS: Sixty-five renal allograft recipients who received treatment with DPP-4 inhibitors (vildagliptin, sitagliptin, or linagliptin) following kidney transplant were enrolled...
March 2016: Endocrinology and Metabolism
Ioannis Tsavdaridis, Dimochristos Papadimitriou, Dora Karanikola, Kostas Kalousis, Areti Katsouda, Maria Mironidou-Tzouveleki
OBJECTIVE: The term Diabetic kidney disease (DKD) refers to any disease of the kidney that is a result of long-term hyperglycemia caused either by diabetes mellitus type 1 (DT1) or type 2 (DT2). When DKD coexists with macro albuminuria or proteinuria the condition is called diabetic nephropathy. DKD is the primary cause of renal failure since it is responsible for the 44% of new cases presented in the U.S.A. in 2008. Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase and is used as a treatment for diabetes since 2006...
September 2015: Hellenic Journal of Nuclear Medicine
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