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Mitsutoshi Asakura, Fumika Karaki, Hideaki Fujii, Koichiro Atsuda, Tomoo Itoh, Ryoichi Fujiwara
Vildagliptin is a potent, orally active inhibitor of dipeptidyl peptidase-4 (DPP-4) for the treatment of type 2 diabetes mellitus. It has been reported that vildagliptin can cause hepatic dysfunction in patients. However, the molecular-mechanism of vildagliptin-induced liver dysfunction has not been elucidated. In this study, we employed an expression microarray to determine hepatic genes that were highly regulated by vildagliptin in mice. We found that pro-inflammatory S100 calcium-binding protein (S100) a8 and S100a9 were induced more than 5-fold by vildagliptin in the mouse liver...
October 19, 2016: Scientific Reports
Elena Succurro, Caterina Palleria, Maria Francesca Ruffo, Raffaele Serra, Franco Arturi, Luca Gallelli
: The fixed dose combination of sitagliptin 50 mg and metformin 850 mg (Janumet ®), is indicated for the treatment of type 2 diabetes mellitus in addition to diet and exercise to improve glycemic control in patients treated with metformin alone. METHODS: We report a 69-year-old man with type 2 diabetes that developed sudden loss of eyebrows and eyelashes about 4 months after the beginning of Janumet ®. Clinical and laboratory findings excluded the presence of systemic or skin diseases able to induce these manifestations, while the Naranjo probability scale documented a possible association between the drug and the adverse drug reaction...
October 14, 2016: Current Drug Safety
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
Hae-Young Lee, Chan-Soon Park, Sang-Hoon Na, Kyung-Jin Kim, Chan Joo Lee, Sungha Park
A 47-year-old woman was admitted via emergency department due to dyspnea NYHA Fc II-III aggravated for 2 months after upper respiratory infection. Her height and body weight were 161 cm / 67 kg. Initial vital signs were 110/70 mmHg - 112 BPM - 24/min - 36.5°C. Chest PA showed cardiomegaly and pulmonary congestion (Figure 1). B-natriuretic peptide level was markedly increased (2002 pg/mL, normal range ≤ 100 pg/mL). The echocardiographic examination showed severely dilated LV cavity (61/72 mm) and severe LV systolic dysfunction (EF 28%) with normal left ventricular wall thickness (9/11 mm) (Figure 2)...
September 2016: Journal of Hypertension
Alexandre Baptista, Inês Teixeira, Sónia Romano, António Vaz Carneiro, Julian Perelman
OBJECTIVE: To conduct a systematic review of cost-effectiveness, cost-utility, and cost-benefit studies of DPP-4 inhibitors for diabetes treatment versus other antidiabetics. METHODS: Three investigators searched the CRD York, Tufts CEA Registry, and MEDLINE databases through 2015. We reviewed all potentially relevant titles and abstracts, and screened full-text articles, according to inclusion criteria. We established a quality score for each study based on a 35-item list...
October 17, 2016: European Journal of Health Economics: HEPAC: Health Economics in Prevention and Care
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
Jan H Cornel, George L Bakris, Susanna R Stevens, Michael Alvarsson, Willem A Bax, Lee-Ming Chuang, Samuel S Engel, Renato D Lopes, Darren K McGuire, Axel Riefflin, Helena Wachslicht Rodbard, Isaac Sinay, Tsvetalina Tankova, Julio Wainstein, Eric D Peterson, Rury R Holman
OBJECTIVE: To evaluate chronic kidney disease (CKD) and cardiovascular outcomes in TECOS (Clinical trial reg. no. NCT00790205, participants with type 2 diabetes and cardiovascular disease treated with sitagliptin, a dipeptidyl peptidase 4 inhibitor, according to baseline estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS: We used data from 14,671 TECOS participants assigned in a double-blind design to receive sitagliptin or placebo added to existing therapy, while aiming for glycemic equipoise between groups...
October 14, 2016: Diabetes Care
R Ravi Shankar, Yuqian Bao, Ping Han, Ji Hu, Jianhua Ma, Yongde Peng, Fan Wu, Lei Xu, Samuel S Engel, Weiping Jia
INTRODUCTION: We evaluated the tolerability and efficacy of the addition of sitagliptin in Chinese patients with type 2 diabetes mellitus (T2DM) on stable insulin therapy alone or in combination with metformin. MATERIALS AND METHODS: Four hundred sixty-seven patients with inadequate glycemic control on insulin (HbA1c ≥7.5% and ≤11%) were randomized 1:1 to receive sitagliptin 100 mg once-daily or matching placebo for 24 weeks. Randomization was stratified based on metformin use (on or not on metformin) and type of insulin (pre-mixed versus intermediate-/long-acting) at screening...
October 14, 2016: Journal of Diabetes Investigation
Hiroshi Nomoto, Hideaki Miyoshi, Tomoo Furumoto, Koji Oba, Hiroyuki Tsutsui, Atsushi Inoue, Tatsuya Atsumi, Naoki Manda, Yoshio Kurihara, Shin Aoki
OBJECTIVES: The DPP-4 inhibitors are incretin-related drugs that improve hyperglycemia in a glucose-dependent manner and have been reported to exert favorable effects on atherosclerosis. However, it has not been fully elucidated whether DPP-4 inhibitors are able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of sitagliptin, a DPP-4 inhibitor, on endothelial function and glycemic metabolism compared with that of the sulfonylurea glimepiride...
2016: PloS One
Michael A Nauck, Melanie Kahle, Oleg Baranov, Carolyn F Deacon, Jens J Holst
AIMS/HYPOTHESIS: GLP-1 receptor agonists and DPP-4 inhibitors both stimulate GLP-1 receptors. Our objective was to determine, whether the addition of sitagliptin to pre-existing therapy with liraglutide changes glycaemic excursions after a mixed meal. METHODS: 16 subjects with type 2 diabetes treated with metformin and liraglutide (1.2 mg/d for ≥ 2 weeks) were randomized (sealed envelopes), within a cross-over design, to be studied on two occasions, after an overnight fast, with (a) sitagliptin (100 mg p...
October 6, 2016: Diabetes, Obesity & Metabolism
I Hoffmanová, P Škrha, A Šedo, M Anděl
No abstract text is available yet for this article.
September 2016: Ultrasound Int Open
Jelka Gabrilovac, Barbara Čupić, Emilija Zapletal, Ognjen Kraus, Jasminka Jakić-Razumović
BACKGROUND: Dipeptidyl peptidase 9 (DPP9) is a relatively new member of the DPPIV family of prolyl dipeptidases which is ubiquitously expressed. Its role in regulation of immune responses and proliferation of epithelial carcinoma cells was reported. There is no data on possible role of DPP9 expressed in skin epithelial cells (keratinocytes) and in dermal fibroblasts. MATERIALS AND METHODS: Transcriptional and protein expression of DPP9 and DPPIV was examined in fibroblasts and keratinocytes isolated from normal human skin...
September 19, 2016: Immunobiology
Thomas Vanhove, Quinten Remijsen, Dirk Kuypers, Pieter Gillard
Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT)-2 inhibitors...
September 14, 2016: Transplantation Reviews
Chin-Hsiao Tseng
This retrospective cohort study evaluated the risk of prostate cancer associated with sitagliptin use in Taiwanese male patients with type 2 diabetes mellitus by using the reimbursement databases of the National Health Insurance. Male patients with newly diagnosed type 2 diabetes mellitus at an age ≥25 years between 1999 and 2010 were recruited. A total of 37,924 ever users of sitagliptin and 426,276 never users were followed until December 31, 2011. The treatment effect of sitagliptin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score...
September 20, 2016: Oncotarget
Ivan Tkáč, Itamar Raz
OBJECTIVE: Data on the possible relationship of gliptin treatment to the incidence of acute pancreatitis have been controversial. The aim of the current study was to combine data on the incidence of acute pancreatitis from three large randomized controlled trials. RESEARCH DESIGN AND METHODS: Three trials designed to test cardiovascular safety and efficacy of add-on treatment with a gliptin were included in the analysis, as follows: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin)...
September 22, 2016: Diabetes Care
Akihiro Nishimura, Shuki Usui, Naoki Kumashiro, Hiroshi Uchino, Azusa Yamato, Daijiro Yasuda, Kaoru Nagasawa, Minoru Okubo, Yasumichi Mori, Takahisa Hirose
Although sitagliptin and repaglinide monotherapies improve postprandial hyperglycemia, the long-term effects and safety of their combination has not been examined. In this randomized 24-week trial of Japanese patients with poor control (HbA1c 7.0-8.5%) by sitagliptin, we divided 40 patients randomly into two equal groups of the repaglinide add-on to sitagliptin (ADD-ON, n=20), or sitagliptin switched to repaglinide (SWITCH, n=20). The meal tolerance test was carried out at weeks 0 and 24. The primary outcomes were changes in HbA1c and area under the curves (AUC) of glucose from the baseline to week 24...
September 17, 2016: Endocrine Journal
Hae-Young Lee, Chan-Soon Park, Sang-Hoon Na, Kyung-Jin Kim, Chan Joo Lee, Sungha Park
A 47-year-old woman was admitted via emergency department due to dyspnea NYHA Fc II-III aggravated for 2 months after upper respiratory infection. Her height and body weight were 161 cm / 67 kg. Initial vital signs were 110/70 mmHg - 112 BPM - 24/min - 36.5°C. Chest PA showed cardiomegaly and pulmonary congestion (Figure 1). B-natriuretic peptide level was markedly increased (2002 pg/mL, normal range ≤ 100 pg/mL). The echocardiographic examination showed severely dilated LV cavity (61/72 mm) and severe LV systolic dysfunction (EF 28%) with normal left ventricular wall thickness (9/11 mm) (Figure 2)...
September 2016: Journal of Hypertension
Ehab Mudher Mikhael
Hypoglycemia is the most common side effects for most glucose-lowering therapies. It constitutes a serious risk that faces diabetic patients who fast during Ramadan (the 9th month in the Islamic calendar). New glucose-lowering classes like dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonist (GLP-1 RA), and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are efficacious in controlling blood glucose level with less tendency to induce hypoglycemia and thus may constitute a good choice for diabetic patients during Ramadan...
2016: Journal of Diabetes Research
Shoichi Kuramitsu, Katsumi Miyauchi, Hiroyoshi Yokoi, Satoru Suwa, Yuji Nishizaki, Takayuki Yokoyama, Shuko Nojiri, Masashi Iwabuchi, Shinichi Shirai, Kenji Ando, Shinya Okazaki, Hiroshi Tamura, Hirotaka Watada, Hiroyuki Daida
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherosclerotic and cardioprotective effects in vitro. However, the impact of DPP-4 inhibitors on coronary plaque remains unclear. We sought to assess the effect of sitagliptin on coronary plaque volume (PV) and stabilization in diabetic patients with acute coronary syndrome (ACS). METHODS: The ESPECIAL-ACS was a prospective, randomized, open-label, parallel group study at 4 Japanese centers to assess the effect of 6-month treatment with sitagliptin on coronary plaque changes in non-culprit lesion in diabetic patients with ACS using serial intravascular ultrasound (IVUS) and integrated backscatter IVUS (IB-IVUS) analysis...
September 15, 2016: Journal of Cardiology
Rimke C Vos, Mariëlle Jp van Avendonk, Hanneke Jansen, Alexander N Goudswaard, Maureen van den Donk, Kees Gorter, Anneloes Kerssen, Guy Ehm Rutten
BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin monotherapy for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control...
September 18, 2016: Cochrane Database of Systematic Reviews
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