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Michishige Terasaki, Munenori Hiromura, Yusaku Mori, Kyoko Kohashi, Hideki Kushima, Makoto Ohara, Takuya Watanabe, Olov Andersson, Tsutomu Hirano
Dipeptidyl peptidase-4 inhibitors (DPP-4is), in addition to their antihyperglycemic roles, have antiatherosclerotic effects. We reported that sodium-glucose cotransporter 2 inhibitors (SGLT2is) suppress atherosclerosis in a glucose-dependent manner in diabetic mice. Here, we investigated the effects of combination therapy with SGLT2i and DPP-4i on atherosclerosis in diabetic mice. SGLT2i (ipragliflozin, 1.0 mg/kg/day) and DPP-4i (alogliptin, 8.0 mg/kg/day), either alone or in combination, were administered to db/db mice or streptozotocin-induced diabetic apolipoprotein E-null (Apoe(-/-) ) mice...
2017: International Journal of Endocrinology
Michaela Luconi, Giulia Cantini, Antonio Ceriello, Edoardo Mannucci
Recently, cardiovascular outcome trials with glucose-lowering drugs used in type 2 diabetes mellitus, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), liraglutide and semaglutide, showed a reduction in cardiovascular events, which had not been observed in trials with other incretin-based drugs, such as lixisenatide or with dipeptidyl peptidase-4 inhibitors (DPP4i). Mechanisms underlying the observed cardiovascular differences between DPP4i and GLP1-RA, and across individual GLP1-RA are poorly understood...
March 2, 2017: International Journal of Cardiology
Huang-Tz Ou, Kai-Cheng Chang, Chung-Yi Li, Jin-Shang Wu
AIMS: Dipeptidyl peptidase-4 inhibitors (DPP4i) are suggested as 2(nd) and 3(rd) add-on antidiabetic treatment for type 2 diabetes. Previous studies only assessed cardiovascular effects of DPP4i as 2(nd) line treatment, included sulfonylurea as only one comparator, and yielded inconclusive results on the risk of heart failure. This study therefore evaluated comparative cardiovascular risks of DPP4i with other 2(nd) and 3(rd) line antidiabetic drugs. METHODS: Based on a large nation-wide diabetic cohort, 113,051 patients with type 2 diabetes newly on metformin-based dual or triple therapy were identified in 2009-2011 and followed until death or 2013...
January 21, 2017: British Journal of Clinical Pharmacology
Yuya Seko, Yoshio Sumida, Saiyu Tanaka, Kojiroh Mori, Hiroyoshi Taketani, Hiroshi Ishiba, Tasuku Hara, Akira Okajima, Atsushi Umemura, Taichiro Nishikawa, Kanji Yamaguchi, Michihisa Moriguchi, Kazuyuki Kanemasa, Kohichiroh Yasui, Shunsuke Imai, Keiji Shimada, Yoshito Itoh
AIM: No pharmacological therapies have been established for non-alcoholic fatty liver disease (NAFLD). Sodium glucose cotransporter 2 inhibitor (SGLT2I) was developed for the treatment of adults with type 2 diabetes mellitus (T2DM). The aim of this retrospective study is to evaluate the efficacy of SGLT2I in NAFLD patients with T2DM. METHODS: Twenty-four biopsy-proven NAFLD patients with T2DM who received SGLT2I for 24 weeks were retrospectively enrolled as the SGLT2I group...
November 2, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Xin Liu, Peng Men, Yuhui Wang, Suodi Zhai, George Liu
BACKGROUND: Adiponectin, an adipose-specific protein, is negatively correlated with pro-atherogenic low-density lipoprotein cholesterol (LDL-C) and other cardiovascular risk factors such as insulin resistance. Therefore, low levels of adiponectin are associated with a higher risk for diabetes and cardiovascular disease. Dipeptidyl peptidase-4 inhibitors (DPP4i) have been used for the treatment of type 2 diabetes mellitus (T2DM) as reversible inhibitors through interacting with DPP4 substrate and increase serum incretins such as glucagon-like peptide-1 (GLP-1)...
November 23, 2016: Lipids in Health and Disease
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...
December 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 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...
January 2017: 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...
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...
March 1, 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
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