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Yochai Birnbaum, Mandeep Bajaj, Jinqiao Qian, Yumei Ye
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor activation delays the progression of diabetic nephropathy (DN) in rodents. The NOD-like receptor 3 (Nlrp3) inflammasome plays an important role in DN. Dipeptidyl peptidase-4 inhibitors (DPP4I) inhibit the degradation of endogenous GLP-1 and various other active substances. We assessed whether DPP4I attenuates diabetes-induced activation of the inflammasome and progression of DN in mice with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM)...
2016: BMJ Open Diabetes Research & Care
Valentina Vellecco, Emma Mitidieri, Antonella Gargiulo, Vincenzo Brancaleone, Danilo Matassa, Thomas Klein, Franca Esposito, Giuseppe Cirino, Mariarosaria Bucci
AIM: To test the effect of linagliptin in non-obese diabetic (NOD) mice, a murine model of type 1 diabetes, to unveil a possible direct cardiovascular action of dipeptidyl peptidase 4 (DPP-4) inhibitors beyond glycaemia control. METHODS: NOD mice were grouped according to glycosuria levels as NODI: none; NODII: high; NODIII: severe. Linagliptin treatment was initiated once they reached NODII levels. Vascular reactivity was assessed ex vivo on aorta harvested from mice upon reaching NODIII level...
July 27, 2016: Diabetes, Obesity & Metabolism
Darren K McGuire, Frans Van de Werf, Paul W Armstrong, Eberhard Standl, Joerg Koglin, Jennifer B Green, M Angelyn Bethel, Jan H Cornel, Renato D Lopes, Sigrun Halvorsen, Giuseppe Ambrosio, John B Buse, Robert G Josse, John M Lachin, Michael J Pencina, Jyotsna Garg, Yuliya Lokhnygina, Rury R Holman, Eric D Peterson
IMPORTANCE: Previous trial results have suggested that dipeptidyl peptidase 4 inhibitor (DPP4i) use might increase heart failure (HF) risk in type 2 diabetes mellitus (T2DM). The DPP4i sitagliptin has been shown to be noninferior to placebo with regard to primary and secondary composite atherosclerotic cardiovascular (CV) outcomes in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS). OBJECTIVE: To assess the association of sitagliptin use with hospitalization for HF (hHF) and related outcomes...
May 1, 2016: JAMA Cardiology
Haruya Kawase, Yasuko K Bando, Kazuyuki Nishimura, Morihiko Aoyama, Akio Monji, Toyoaki Murohara
BACKGROUND: To address the impact of antidiabetic drugs on cardiovascular safety is a matter of clinical concern. Preclinical studies revealed that various protective effects of dipeptidyl peptidase-4 inhibitor (DPP4i) on cardiovascular disease; however, its impact of on hypertension remains controversial. METHODS AND RESULTS: Teneligliptin (TEN; 10mg/kg/day/p.o.) ameliorates hypertension and cardiac remodeling by normalizing a rise of angiotensin-II (AngII) that specifically observed in spontaneously hypertensive rats (SHR)...
September 2016: Journal of Molecular and Cellular Cardiology
John-Michael Gamble, Jamie M Thomas, Laurie K Twells, William K Midodzi, Sumit R Majumdar
There is limited comparative effectiveness evidence to guide approaches to managing diabetes in individuals failing metformin monotherapy. Our aim was to compare the incidence of all-cause mortality and major adverse cardiovascular events (MACEs) among new metformin monotherapy users initiating a dipeptidyl-peptidase-4 inhibitor (DPP4i), glucagon-like peptide-1 receptor agonist (GLP-1RA), sulfonylurea (SU), thiazolidinedione, or insulin.We conducted a cohort study using the UK-based Clinical Practice Research Datalink...
June 2016: Medicine (Baltimore)
Jan W Eriksson, Johan Bodegard, David Nathanson, Marcus Thuresson, Thomas Nyström, Anna Norhammar
AIMS: There are safety concerns related to sulphonylurea treatment. The objective of this nationwide study was to compare the risk of cardiovascular disease (CVD), all-cause mortality and severe hypoglycemia in patients with type 2 diabetes (T2D) starting second-line treatment with either metformin+sulphonylurea or metformin+dipeptidyl peptidase-4 inhibitor (DPP-4i). METHODS: All patients with T2D in Sweden who initiated second-line treatment with metformin+sulphonylurea or metformin+DPP-4i during 2006-2013 (n=40,736 and 12,024, respectively) were identified in this nationwide study...
July 2016: Diabetes Research and Clinical Practice
Yeong Gi Kim, Se Hee Min, Seokyung Hahn, Tae Jung Oh, Kyong Soo Park, Young Min Cho
AIMS: To compare the efficacy and safety of the addition of a dipeptidyl peptidase-4 (DPP-4) inhibitor or a placebo in patients with type 2 diabetes inadequately controlled with insulin. METHODS: We searched randomised controlled trials (RCTs) from MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials and the online registry. Studies of at least 12week treatment duration were eligible if they were RCTs in patients with type 2 diabetes comparing addition of a DPP-4 inhibitor to insulin therapy (INS/DPP4i) with addition of a placebo to insulin therapy (INS/PCB) and contained information on the change in glycated haemoglobin (HbA1c) from baseline...
June 2016: Diabetes Research and Clinical Practice
Se Hee Min, Jeong-Hwa Yoon, Seokyung Hahn, Young Min Cho
BACKGROUND: Both sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors can be used to treat patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled with insulin therapy, and yet there has been no direct comparison of these two inhibitors. METHODS: We searched MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials, and through June 2015. Randomized controlled trials (RCTs) published in English that compare SGLT2 inhibitor plus insulin (SGLT2i/INS) with placebo plus insulin or DPP4 inhibitor plus insulin (DPP4i/INS) with placebo plus insulin in patients with T2DM were selected...
May 7, 2016: Diabetes/metabolism Research and Reviews
Wen-Hsuan Hou, Kai-Cheng Chang, Chung-Yi Li, Huang-Tz Ou
This is the first large longitudinal cohort study to investigate the putative association of severe joint pain (SJP) with dipeptidyl peptidase-4 inhibitor (DPP4i) use in patients with type 2 diabetes. The propensity score-matched population-based cohort study was performed between 2009 and 2013 in a group of type 2 diabetes patients with stable metformin use. In total, 4743 patients with type 2 diabetes used a DPP4i as the second-line antidiabetic drug (ie, DPP4i users), and the same number of matched non-DPP4i users was selected...
September 2016: Pain
Huang-Tz Ou, Kai-Cheng Chang, Ya-Ming Liu, Jin-Shang Wu
BACKGROUND: Studies from other countries have indicated that the utilization patterns of antidiabetic drugs changed significantly after the introduction of newer classes of antidiabetic drugs (e.g., dipeptidyl peptidase-4 inhibitors; DDP4i). Evidence on recent trends of antidiabetic drug utilization in Taiwan is lacking, especially for the time after newer classes of drugs (e.g., DPP4i) were introduced. This study therefore assessed (1) recent trends in the utilization and spending on antidiabetic drugs, (2) change in utilization patterns after newer classes of antidiabetic drugs were introduced, and (3) factors associated with the choice of newer versus older classes of antidiabetic drugs...
April 6, 2016: Journal of Diabetes
Atsushi Iida, Yusuke Seino, Ayako Fukami, Ryuya Maekawa, Daisuke Yabe, Shinobu Shimizu, Keita Kinoshita, Yusuke Takagi, Takako Izumoto, Hidetada Ogata, Kota Ishikawa, Nobuaki Ozaki, Shin Tsunekawa, Yoji Hamada, Yutaka Oiso, Hiroshi Arima, Yoshitaka Hayashi
AIMS/HYPOTHESIS: The action of incretin hormones including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) is potentiated in animal models defective in glucagon action. It has been reported that such animal models maintain normoglycaemia under streptozotocin (STZ)-induced beta cell damage. However, the role of GIP in regulation of glucose metabolism under a combination of glucagon deficiency and STZ-induced beta cell damage has not been fully explored...
July 2016: Diabetologia
Helena M de Wit, Maarten Te Groen, Maroeska M Rovers, Cees J Tack
AIMS: The size of the placebo response in type 2 diabetes (T2DM) treatment and its relation to the route of drug administration have not been systematically reviewed. We aimed to determine weight loss, change in HbA1c and incidence of adverse events after treatment with injectable placebo GLP-1 receptor agonist (GLP-1ra), compared with oral placebo DPP-4 inhibitor (DPP-4i) and placebo SGLT-2 inhibitor (SGLT-2i). METHODS: PubMed, EMBASE and Central were searched up to September 2014 for randomized placebo controlled trials investigating GLP-1ra, DPP-4i or SGLT2-i...
July 2016: British Journal of Clinical Pharmacology
Huang-Tz Ou, Kai-Cheng Chang, Chung-Yi Li, Jin-Shang Wu
BACKGROUND: Several antidiabetic drugs (i.e., sulfonylureas; SU, rosiglitazone) have been reported to be associated with increased risks of cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM). Dipeptidyl peptidase-4 inhibitors (DPP4i) are newly available antidiabetic drugs. Most studies only compared DPP4i with a placebo or SU, or targeted a specific CVD event of interest (i.e., heart failure; HF). Comparative research of CVD risks of DPP4i with other antidiabetic drugs (i...
2016: Cardiovascular Diabetology
Morihiko Aoyama, Haruya Kawase, Yasuko K Bando, Akio Monji, Toyoaki Murohara
BACKGROUND: Ample evidence demonstrates cardiovascular protection by incretin-based therapy using dipeptidyl peptidase 4 inhibitor (DPP4i) and glucagon-like peptide-1 (GLP-1) under either diabetic or nondiabetic condition. Their action on myocardium is mediated by the cyclic AMP (cAMP) signal; however, the pathway remains uncertain. This study was conducted to address the effect of DPP4i/GLP-1/cAMP axis on cardiac dysfunction and remodeling induced by pressure overload (thoracic aortic constriction [TAC]) independently of diabetes mellitus...
January 2016: Circulation. Heart Failure
M Shoji, K Kobayashi, M Takemoto, Y Sato, K Yokote
Diabetic nephropathy has dramatically increased worldwide. In this study, we measured urinary podocalyxin in 240 patients with diabetes. The relationship between urinary podocalyxin and clinical parameters and the effects of dipeptidyl peptidase-4 inhibitors (DPP4i) and alpha-glucosidase inhibitor (a-GI) on urinary podocalyxin levels were examined. Urinary podocalyxin levels were significantly higher in patients with microalbuminuria than in those with normoalbuminuria. Urinary podocalyxin levels were also significantly related to albumin-to-creatinine ratio...
2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
C Triplitt, C Solis-Herrera, E Cersosimo, M Abdul-Ghani, Ralph A Defronzo
INTRODUCTION: Many patients with type 2 diabetes mellitus (T2DM) fail to achieve the desired A1c goal because the antidiabetic medications used do not correct the underlying pathophysiologic abnormalities and monotherapy is not sufficiently potent to reduce the A1c to the 6.5 - 7.0% range. Insulin resistance and islet (beta and alpha) cell dysfunction are major pathophysiologic abnormalities in T2DM. We examine combination therapy with linagliptin plus empagliflozin as a therapeutic approach for the treatment of inadequately controlled T2DM patients...
2015: Expert Opinion on Pharmacotherapy
J Yoon, S H Min, S Hahn, Y M Cho
No abstract text is available yet for this article.
November 2015: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Rogier Wvan der Zanden, Frank de Vries, Arief Lalmohamed, Johanna H M Driessen, Anthonius de Boer, Gernot Rohde, Cees Neef, Casper den Heijer
BACKGROUND: Dipeptidyl-peptidase-4 inhibitors (DPP4Is) are drugs for the treatment of type 2 diabetes mellitus (T2DM). There is increasing evidence that DPP4Is may result in suppression of the immune system and may increase the risk of infections such as pneumonia. Aim of this study was to evaluate the association between the use of DPP4Is and the risk of pneumonia in a population-based study. METHODS: We conducted a population-based cohort study using data from the world's largest primary care database, the UK Clinical Practice Research Datalink (CPRD)...
2015: PloS One
Asuka Morita, Eri Mukai, Ayano Hiratsuka, Tomozumi Takatani, Toshihiko Iwanaga, Eun Young Lee, Takashi Miki
Although the two anti-diabetic drugs, dipeptidyl peptidase-4 inhibitors (DPP4is) and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP1RAs), have distinct effects on the dynamics of circulating incretins, little is known of the difference in their consequences on morphology and function of pancreatic islets. We examined these in a mouse model of β cell injury/regeneration. The model mice were generated so as to express diphtheria toxin (DT) receptor and a fluorescent protein (Tomato) specifically in β cells...
March 2016: Endocrine
Sunghwan Suh, Gi Hyeon Seo, Chang Hee Jung, Mee-Kyoung Kim, Sang-Man Jin, You-Cheol Hwang, Byung-Wan Lee, Jae Hyeon Kim
BACKGROUND: We assessed the association of dipeptidyl peptidase 4 inhibitors (DPP4i) with hospitalization for heart failure (HF) using the Korean Health Insurance claims database. METHODS: We collected data on newly prescribed sitagliptin, vildagliptin, and pioglitazone between January 1, 2009 and December 31, 2012 (mean follow-up of 336.8 days) to 935,519 patients with diabetes (518,614 males and 416,905 females) aged 40 to 79 years (mean age of 59.4 years). RESULTS: During the study, 998 patients were hospitalized for primary HF (115...
June 2015: Diabetes & Metabolism Journal
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