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Diabetes sglt2

Kyu Yon G Cho, Akinobu Nakamura, Kazuno Omori, Takahiro Takase, Aika Miya, Naoki Manda, Yoshio Kurihara, Shin Aoki, Tatsuya Atsumi, Hideaki Miyoshi
The effects of dapagliflozin and pioglitazone on body weight and glycemic control were compared in patients with type 2 diabetes mellitus. Seventy-one patients on pioglitazone (PIO) were either switched to dapagliflozin (DAP, n = 36) at 5 mg per day or continued on PIO (n = 35). Primary endpoints were superiority of weight loss and non-inferiority of HbA1c level after 24 weeks with DAP. Body weight decrease was greater with DAP than with PIO (75.3 ± 14.9 to 71.3 ± 15.1 kg vs. 74.7 ± 13.8 to 75.2 ± 13.9 kg; p < 0...
October 12, 2018: Diabetes, Obesity & Metabolism
Julio Rosenstock, Chantal Mathieu, Hungta Chen, Ricardo Garcia-Sanchez, Gabriela Luporini Saraiva
OBJECTIVE: This analysis compared the efficacy and safety of the sodium-glucose cotransporter-2 (SGLT2) inhibitor, dapagliflozin, and the dipeptidyl peptidase-4 (DPP4) inhibitor, saxagliptin, both added on to metformin. MATERIALS AND METHODS: This was a post-hoc analysis from a double-blind, randomized, 24-week clinical trial (NCT01606007) of patients with type 2 diabetes (T2D) inadequately controlled with metformin. We compared the dapagliflozin 10 mg (n = 179) and saxagliptin 5 mg (n = 176) treatment arms...
August 2018: Archives of Endocrinology and Metabolism
Fumitaka Soga, Hidekazu Tanaka, Kazuhiro Tatsumi, Yasuhide Mochizuki, Hiroyuki Sano, Hiromi Toki, Kensuke Matsumoto, Junya Shite, Hideyuki Takaoka, Tomofumi Doi, Ken-Ichi Hirata
BACKGROUND: The objective of this study was to investigate the impact of sodium glucose cotransporter type 2 (SGLT2) inhibitors on left ventricular (LV) diastolic function of type 2 diabetes mellitus (T2DM) patients with heart failure (HF). METHODS: This trial was a prospective multicenter study of 58 T2DM patients with stable HF at five institutions in Japan. Patients who had been taking at least one antidiabetic drugs other than SGLT2 inhibitors started the administration of 5 mg/day of dapagliflozin...
October 8, 2018: Cardiovascular Diabetology
Kwong-Man Ng, Yee-Man Lau, Vidhu Dhandhania, Zhu-Jun Cai, Yee-Ki Lee, Wing-Hon Lai, Hung-Fat Tse, Chung-Wah Siu
Empagliflozin, a sodium-glucose co-transporter (SGLT) inhibitor, reduces heart failure and sudden cardiac death but the underlying mechanisms remain elusive. In cardiomyocytes, SGLT1 and SGLT2 expression is upregulated in diabetes mellitus, heart failure, and myocardial infarction. We hypothesise that empagliflozin exerts direct effects on cardiomyocytes that attenuate diabetic cardiomyopathy. To test this hypothesis, cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) were used to test the potential effects of empagliflozin on neutralization of cardiac dysfunction induced by diabetic-like cultures...
October 5, 2018: Scientific Reports
Melanie J Davies, David A D'Alessio, Judith Fradkin, Walter N Kernan, Chantal Mathieu, Geltrude Mingrone, Peter Rossing, Apostolos Tsapas, Deborah J Wexler, John B Buse
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, and surgical interventions, are recommended...
October 4, 2018: Diabetes Care
Christopher P Cannon, Darren K McGuire, Richard Pratley, Sam Dagogo-Jack, James Mancuso, Susan Huyck, Bernard Charbonnel, Weichung J Shih, Silvina Gallo, Urszula Masiukiewicz, Gregory Golm, Francesco Cosentino, Brett Lauring, Steven G Terra
BACKGROUND: Ertugliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), approved in the United States and European Union to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). The VERTIS cardiovascular (CV) outcomes trial (NCT01986881) has a primary objective to demonstrate non-inferiority of ertugliflozin versus placebo on major adverse CV events: time to the first event of CV death, nonfatal myocardial infarction, or nonfatal stroke. Secondary objectives are to demonstrate superiority of ertugliflozin versus placebo on time to: 1) the composite outcome of CV death or hospitalization for heart failure (HF); 2) CV death; and 3) the composite outcome of renal death, dialysis/transplant, or doubling of serum creatinine from baseline...
September 5, 2018: American Heart Journal
Leigh Perreault
OBJECTIVE: The purpose of this review is to expose the surprising prevalence of diabetes-related complications in people with persistent prediabetes, and hence, to expand the paradigm of diabetes prevention to include the prevention of complications related to both hyperglycemia and obesity. METHODS: Published literature was reviewed. RESULTS: Approximately 84 million Americans have prediabetes, 85% of whom are overweight or obese. Although the incidence of diabetes-related complications is lower in people with prediabetes vs...
October 5, 2018: Endocrine Practice
Melanie J Davies, David A D'Alessio, Judith Fradkin, Walter N Kernan, Chantal Mathieu, Geltrude Mingrone, Peter Rossing, Apostolos Tsapas, Deborah J Wexler, John B Buse
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication and surgical interventions, are recommended...
October 5, 2018: Diabetologia
Kazuo Kobayashi, Masao Toyoda, Moritsugu Kimura, Nobuo Hatori, Takayuki Furuki, Hiroyuki Sakai, Masahiro Takihata, Tomoya Umezono, Shun Ito, Daisuke Suzuki, Hiroshi Takeda, Akira Kanamori, Hisakazu Degawa, Hareaki Yamamoto, Hideo Machimura, Atsuko Mokubo, Keiichi Chin, Mitsuo Obana, Toshimasa Hishiki, Kouta Aoyama, Shinichi Nakajima, Shinichi Umezawa, Hidetoshi Shimura, Togo Aoyama, Kazuyoshi Sato, Masaaki Miyakawa
AIM: The aim of this study was to assess the renal effects of the glucose-lowering SGLT2 inhibitors in Japanese type 2 diabetes mellitus patients with chronic kidney disease. METHODS: The Kanagawa Physicians Association maintains a registry of patients who visit their 31 clinics. Clinical data of type 2 diabetes mellitus patients with chronic kidney disease, who were prescribed SGLT2 inhibitors in addition to other treatments, were collected and analysed. RESULTS: SGLT2i was associated with a fall in HbA1c from 64...
October 4, 2018: Diabetes & Vascular Disease Research
Sonia Rocha, Daniela Ribeiro, Eduarda Fernandes, Marisa Freitas
The use of anti-diabetic drugs has been increasing worldwide and the evolution of therapeutics has been enormous. Still, the currently available anti-diabetic drugs do not present the desired efficacy and are generally associated with serious adverse side effects. Thus, entirely new interventions, addressing the underlying etiopathogenesis of type 2 diabetes mellitus, are required. Chalcones, secondary metabolites of terrestrial plants and precursors of the flavonoids biosynthesis, have been used for a long time in the traditional medicine due to their wide-range of biological activities, from which the anti-diabetic activity stands out...
October 1, 2018: Current Medicinal Chemistry
Pavel Balazki, Stephan Schaller, Thomas Eissing, Thorsten Lehr
The early stage of diabetes mellitus is characterized by increased glomerular filtration rate (GFR), known as hyperfiltration, which is believed to be one of the main causes leading to renal injury in diabetes. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to be able to reverse hyperfiltration in some patients. We developed a mechanistic computational model of kidney that explains the interplay of hyperglycemia and hyperfiltration and integrates the pharmacokinetics/pharmacodynamics (PK/PD) of the SGLT2i dapagliflozin...
September 30, 2018: CPT: Pharmacometrics & Systems Pharmacology
F Bonnet, A J Scheen
Chronic low-grade inflammation is a recognized key feature associated with type 2 diabetes mellitus (T2DM) and its complications. In prospective randomized trials, sodium-glucose cotransporter type 2 (SGLT2) inhibitors have demonstrated benefits related to several cardiovascular and renal risk factors, including HbA1c , blood pressure, body weight, renal hyperfiltration, and improvement of cardiorenal outcomes. SGLT2 inhibitors may improve adipose tissue function and induce decreases in serum leptin, TNF-α and IL-6 while increasing adiponectin...
September 26, 2018: Diabetes & Metabolism
Naresh Kumar, Ankit Garg, Deepak L Bhatt, Sandra Sabongui, Naveen Gupta, Sundeep Chaudhry, Ross Arena, Subodh Verma
SGLT2 inhibitors have been shown to prevent heart failure and reduce cardiovascular death in patients with type 2 diabetes (T2DM) and cardiovascular disease (CVD). Whether or not SGLT2 inhibitors improve indices of cardiorespiratory fitness (CRF), an independent predictor of mortality in patients with CVD, remains unknown. We evaluated the effects of empagliflozin on indices of CRF in patients with T2DM. Twenty patients with T2DM received either empagliflozin 10mg or usual care. Baseline and 3 to 6-month post-treatment measurements of CRF were evaluated using CPET on a cycle ergometer...
September 28, 2018: Canadian Journal of Physiology and Pharmacology
Georgia E Fouli, Luigi Gnudi
Diabetic nephropathy is the commonest cause of end-stage renal disease and affects between 30 and 45% of patients with diabetes mellitus. There is no cure for diabetic nephropathy and the current management of this condition includes glycaemic control, blockade of the renin-angiotensin aldosterone system and lifestyle changes. However, many patients eventually progress to end-stage renal disease. The exact pathogenesis of diabetic nephropathy is still being researched, and recent advances have led to the development of several novel potential therapeutic targets...
September 26, 2018: Nephron
Hyun Sun Park, Youn Joo Jung, Dong-Young Lee, Kyoung Hyoub Moon, Beom Kim, Hae Won Kim
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are effective for overweight diabetic patients through the induction of glucosuria. However, SGLT2 inhibitors are not recommended for patients with advanced chronic kidney disease (CKD) because they may aggravate renal function and thus become less effective in controlling blood glucose in this patient population. We suggest that adequate hydration would be helpful to prevent the side effects of SGLT2 inhibitors in diabetic patients with advanced CKD. In this study, we review five cases of SGLT2 inhibitor therapy, specifically with dapagliflozin, for the treatment of diabetes mellitus in patients with advanced CKD...
September 2018: Kidney Research and Clinical Practice
P C Lee, S Ganguly, S-Y Goh
With their novel, insulin-independent mechanism, sodium-glucose cotransporter-2 (SGLT2) inhibitors are a major turning point in the management of type 2 diabetes mellitus. At present, there are several SGLT2 inhibitors available or in development, and these oral anti-hyperglycaemic agents lower plasma glucose through the inhibition of SGLT2-mediated reuptake of filtered glucose in the kidney. This unique mechanism of action is also expected to result in other beneficial effects, such as weight loss and blood pressure reduction...
September 25, 2018: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Clement Lo, Tadashi Toyama, Ying Wang, Jin Lin, Yoichiro Hirakawa, Min Jun, Alan Cass, Carmel M Hawley, Helen Pilmore, Sunil V Badve, Vlado Perkovic, Sophia Zoungas
BACKGROUND: Diabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co-exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD make glucose-lowering challenging, increasing the risk of hypoglycaemia. Glucose-lowering agents have been mainly studied in people with near-normal kidney function. It is important to characterise existing knowledge of glucose-lowering agents in CKD to guide treatment. OBJECTIVES: To examine the efficacy and safety of insulin and other pharmacological interventions for lowering glucose levels in people with diabetes and CKD...
September 24, 2018: Cochrane Database of Systematic Reviews
Kazuomi Kario, Satoshi Hoshide, Yukie Okawara, Naoko Tomitani, Kenji Yamauchi, Hiroyuki Ohbayashi, Naoki Itabashi, Yuri Matsumoto, Hiroshi Kanegae
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on several cardiometabolic biomarkers, but this is not sufficient to fully explain the significant reduction in cardiovascular risk and mortality reported with SGLT2 inhibitor treatment in patients with diabetes mellitus. The 8-week, randomized, open-label SHIFT-J study investigated the effects of adding canagliflozin vs intensified antihyperglycemic therapy on nocturnal home blood pressure (BP) in patients with poorly controlled type 2 diabetes and nocturnal BP on existing therapy...
October 2018: Journal of Clinical Hypertension
Vasilis Tsimihodimos, Sebastien Filippas-Ntekouan, Moses Elisaf
Sodium Glucose Cotransporters 1 (SGLT1) play important roles in the intestinal absorption of glucose and the renal reabsorption of glucose, especially in patients with uncontrolled diabetes and those receiving SGLT2 inhibitors. As a consequence, the inhibition of SGLT1 transporters may represent an interesting therapeutic option in patients with diabetes. However, genetic models of SGLT1 inactivation indicate that the malfunction of these transporters may have adverse effects on various tissues. In this review, we discuss the available evidence on the beneficial and detrimental effects that the inhibition of SGLT1 transporters might have...
September 18, 2018: European Journal of Pharmacology
Giulia Ferrannini, Lars Rydén
Cardiovascular (CV) disease (CVD) is the main cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Despite optimal glycaemic control, standard antihyperglycaemic therapy failed to impact CV events in intervention trials; therefore, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) issued a guidance to the pharmaceutical industry to specifically assess the CV outcomes and safety of new glucose-lowering drugs. Amongst them, sodium-glucose transporter 2 (SGLT2) inhibitors proved to not only provide good tolerance, few adverse effects, and good glycometabolic control, but also striking reduction in the risk of CV events...
September 28, 2018: Clinical Science (1979-)
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