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https://www.readbyqxmd.com/read/28323955/rapid-onset-of-diabetic-ketoacidosis-following-sglt2-inhibition-in-a-patient-with-unrecognized-acromegaly
#1
Marino Quarella, Daniel Walser, Michael Brändle, Jean-Yves Fournier, Stefan Bilz
Context: Diabetic ketoacidosis has been described as a rare complication of acromegaly and may be observed in 1% of affected patients. The well described direct lipolytic effect of growth hormone results in increased availability of free fatty acids (FFA) for hepatic ketogenesis and is an important pathogenic event. More recently, ketoacidosis has been identified as an important complication of sodium-glucose-transport-protein 2 inhibitors (SGLT2i). Increased pancreatic glucagon secretion, impaired renal ketone body clearance and an increase in FFA concentrations secondary to decreased insulin concentrations are likely precipitating factors...
February 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28304146/liraglutide-acutely-suppresses-glucagon-lipolysis-and-ketogenesis-in-type-1-diabetes
#2
Manisha Garg, Husam Ghanim, Nitesh D Kuhadiya, Kelly Green, Jeanne Hejna, Sanaa Abuaysheh, Barrett Torre, Manav Batra, Antoine Makdissi, Ajay Chaudhuri, Paresh Dandona
In view of the occurrence of diabetic ketoacidosis associated with the use of sodium-glucose transport protein-2 (SGLT2) inhibitors in patients with type 1 diabetes (T1DM) and the relative absence of this complication in patients treated with liraglutide in spite of reductions in insulin doses, we investigated the effect of liraglutide on ketogenesis. Twenty-six patients with inadequately controlled T1DM were randomly divided into two groups of 13 patients each. After an overnight fast, patients were injected, subcutaneously, with either liraglutide 1...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28303514/euglycemic-ketosis-in-patients-with-type-2-diabetes-on-sglt2-inhibitor-therapy-an-emerging-problem-and-solutions-offered-by-diabetes-technology
#3
A Pfützner, D Klonoff, L Heinemann, N Ejskjaer, J Pickup
Diabetic ketoacidosis is an infrequent but life-threatening acute complication of diabetes, affecting predominantly patients with type 1 diabetes, children, and pregnant women, where ketosis is usually associated with marked hyperglycemia. Recently, an increasing number of cases have been reported of euglycemic diabetic ketoacidosis in patients with type 2 diabetes receiving sodium-glucose cotransporter 2 inhibitor treatment in routine practice. There is a minor, but not negligible diabetic ketoacidosis risk associated with this drug class, which was not seen in randomized clinical trials...
March 17, 2017: Endocrine
https://www.readbyqxmd.com/read/28291655/the-cardiovascular-safety-trials-of-dpp-4-inhibitors-glp-1-agonists-and-sglt2-inhibitors
#4
REVIEW
Matthew H Secrest, Jacob A Udell, Kristian B Filion
In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure...
April 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28276972/pharmacotherapy-of-treatment-resistant-type-2-diabetes
#5
André J Scheen
Despite type 2 diabetes (T2D) management offers a variety of pharmacological interventions targeting different defects, numerous patients remain with persistent hyperglycaemia responsible for severe complications. Unlike resistant hypertension, treatment resistant T2D is not a classical concept although it is a rather common observation in clinical practice. Areas covered: This article proposes a definition for 'treatment resistant diabetes', analyses the causes of poor glucose control despite standard therapy, briefly considers the alternative approaches to glucose-lowering pharmacotherapy and finally describes how to overcome poor glycaemic control, using innovative oral or injectable combination therapies...
March 1, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28251513/intensifying-treatment-beyond-monotherapy-in-type-2-diabetes-mellitus-where-do-newer-therapies-fit
#6
REVIEW
Alexander Kuhn, Jean Park, Adline Ghazi, Vanita R Aroda
PURPOSE OF REVIEW: Guidelines for a standard second diabetes medication for the treatment of type 2 diabetes (T2DM) have yet to be established. The rapid increase in the number of newer therapies available makes the choice more difficult. Thus, we reviewed clinical trial evidence evaluating newer therapies available for treatment intensification beyond monotherapy. RECENT FINDINGS: Head-to-head studies comparing newer therapies versus traditional (i.e., sulfonylurea) approaches consistently find lower incidence of hypoglycemia and weight gain with newer therapies...
March 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28177187/efficacy-and-safety-of-canagliflozin-as-add-on-therapy-to-teneligliptin-in-japanese-patients-with-type-2-diabetes-mellitus-results-of-a-24-week-randomised-double-blind-placebo-controlled-trial
#7
Takashi Kadowaki, Nobuya Inagaki, Kazuoki Kondo, Kenichi Nishimura, Genki Kaneko, Nobuko Maruyama, Nobuhiro Nakanishi, Hiroaki Iijima, Yumi Watanabe, Maki Gouda
AIMS: To investigate efficacy and safety of the sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin administered as add-on therapy to the dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial in Japanese patients with T2DM who had inadequate glycaemic control with teneligliptin. Patients were randomised to receive teneligliptin 20 mg plus either canagliflozin 100 mg (T + C, n = 70) or placebo (T + P, n = 68) once daily...
February 8, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28151518/-type-2-diabetes-treatment-and-cardiovascular-risk-what-can-we-learn-from-trials
#8
Agostino Consoli, Fabrizio Febo
Diabetes treatment should include drugs with absolutely no adverse effects toward cardiovascular risk. Indeed, it would be advisable to use drugs with intrinsic protective effect against the risk of cardiovascular events. Intervention trials aiming at demonstrating a protective cardiovascular effect of very tight glucose control have produced controversial results. It is commonly perceived, however, that early intervention with safe treatment strategies is likely to be beneficial. In regard to safety, in the attempt to firmly establish cardiovascular safety of new drugs for diabetes, Government Authorities have mandated that cardiovascular safety trials need to be performed for all new drugs registered for diabetes treatment...
December 2016: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28151517/-effects-of-glucagon-like-peptide-1-receptor-agonists-on-cardiovascular-risk-factors-and-the-cardiovascular-system
#9
Teresa Vanessa Fiorentino, Giorgio Sesti
The results of the cardiovascular outcome trials comparing the SGLT2 inhibitor empagliflozin and the glucagon-like peptide-1 receptor agonist liraglutide to placebo have been recently published. Interestingly, empagliflozin and liraglutide treatments significantly reduce cardiovascular events in subjects with type 2 diabetes. The mechanisms underlying the observed cardioprotective effects of empagliflozin and liraglutide are speculative and future studies are needed to better understand these results. However, since reduction in the primary outcome was evident 3 months after starting empagliflozin and 24 months after starting liraglutide, it is tempting to hypothesize that the cardiovascular benefits observed in diabetic patients treated with empagliflozin are due to its hemodynamic effects and to metabolic substrate shift induced by the mild and persistent hyperketonemia, while the positive effects of liraglutide treatment may be attributable to biologic changes of atherosclerotic lesions...
December 2016: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28128510/determinants-of-the-increase-in-fasting-plasma-ketone-concentration-during-sglt2-inhibition-in-ngt-ifg-and-t2dm-patients
#10
Hussein Al Jobori, Giuseppe Daniele, John Adams, Eugenio Cersosimo, Curtis Triplitt, Ralph A DeFronzo, Muhammad Abdul-Ghani
AIM: To examine metabolic factors that influence ketone production after sodium-glucose cotransport inhibitor (SGLT2) administration RESEARCH DESIGN AND METHODS: Fasting plasma glucose, insulin, glucagon, free fatty acid and ketone concentrations were measured in 15 type 2 diabetes mellitus (T2DM) and 16 non-diabetic subjects before and at 1 and 14 days after treatment with empagliflozin. RESULTS: Empagliflozin caused 38 mg/dl reduction in the fasting plasma glucose (FPG) concentration in T2DM patients...
January 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-non-alcoholic-fatty-liver-disease-with-type-2-diabetes-mellitus
#11
REVIEW
Yoshio Sumida, Yuya Seko, Masashi Yoneda
Liver-related diseases are the leading causes of death in patients with type 2 diabetes mellitus (T2DM) in Japan. Type 2 diabetes mellitus is closely associated with non-alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma and hepatic failure. Non-alcoholic steatohepatitis can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM...
December 26, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27990776/sglt2-inhibitor-use-and-dietary-carbohydrate-intake-in-japanese-individuals-with-type-2-diabetes-a-randomized-open-label-3-arm-parallel-comparative-exploratory-study
#12
Daisuke Yabe, Masahiro Iwasaki, Hitoshi Kuwata, Takuya Haraguchi, Yoshiyuki Hamamoto, Takeshi Kurose, Kiminobu Sumita, Hitoshi Yamazato, Shigeto Kanada, Yutaka Seino
This study investigated safety and efficacy of the SGLT2 inhibitor luseogliflozin under differing carbohydrate intake in Japanese individuals with type 2 diabetes (T2D). Subjects were randomly assigned to three carbohydrate-adjusted meals for 14 days (Days 1-14) [HC-HGI, 55% total energy carbohydrate (TEC) and high glycemic index (GI); HC-LGI, 55% TEC and low GI; and LC-HGI, 40% TEC and high GI]. All subjects received luseogliflozin for the last 7 days (Days 8-14); continuous glucose monitoring (CGM) before and after luseogliflozin treatment (Days 5-8 and Days 12-15); and blood tests on Days 1, 8, and 15...
December 19, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27889414/changes-in-glucose-induced-plasma-active-glucagon-like-peptide-1-levels-by-co-administration-of-sodium-glucose-cotransporter-inhibitors-with-dipeptidyl-peptidase-4-inhibitors-in-rodents
#13
Takahiro Oguma, Chiaki Kuriyama, Keiko Nakayama, Yasuaki Matsushita, Kumiko Hikida, Minoru Tsuda-Tsukimoto, Akira Saito, Kenji Arakawa, Kiichiro Ueta, Masabumi Minami, Masaharu Shiotani
We investigated whether structurally different sodium-glucose cotransporter (SGLT) 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4) inhibitors, could enhance glucagon-like peptide-1 (GLP-1) secretion during oral glucose tolerance tests (OGTTs) in rodents. Three different SGLT inhibitors-1-(β-d-Glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene (GTB), TA-1887, and canagliflozin-were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1) elevation and suppressed glucose excursions in both normal and diabetic rodents...
December 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27765008/sglt2-inhibitors-in-diabetes-mellitus-treatment
#14
Juan Rosas-Guzmán, Juan Rosas-Saucedo, Alma R J Romero-García
Type 2 Diabetes Mellitus (T2DM) is a chronic illness with high prevalence in Mexico, Latin-America, and the world and is associated to high morbidity, disability, and mortality rate, especially in developing countries. T2DM physiopathology is very complex; insulin resistance in the muscle, liver, and adipose tissue, a reduction in the production of incretins (mainly GLP-1) in the intestine, increased glucagon synthesis, an insufficient response of insulin generation, and increased glucose reabsorption in the kidney lead all together to an hyperglycemic state, which has been closely associated with the development of micro and macrovascular complications...
August 29, 2016: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/27701934/impact-of-empa-reg-outcome-%C3%A2-on-the-management-of-type-2-diabetes-mellitus-a-review-for-primary-care-physicians
#15
REVIEW
Soe Naing, Anupama Poliyedath, Stutee Khandelwal, Teresa Sigala
Cardiovascular (CV) disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Most published trials of glucose-lowering agents have shown no significant CV benefit or increased risk of death or heart failure, with the exception of metformin. Three novel classes of glucose-lowering agents, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and sodium glucose cotransporter 2 (SGLT2) inhibitors, have been approved by the U.S. Food and Drug Administration for the treatment of T2DM in the United States and have also been available in other parts of the world in the past decade...
November 2016: Postgraduate Medicine
https://www.readbyqxmd.com/read/27651331/exenatide-once-weekly-plus-dapagliflozin-once-daily-versus-exenatide-or-dapagliflozin-alone-in-patients-with-type-2-diabetes-inadequately-controlled-with-metformin-monotherapy-duration-8-a-28-week-multicentre-double-blind-phase-3-randomised-controlled-trial
#16
Juan P Frías, Cristian Guja, Elise Hardy, Azazuddin Ahmed, Fang Dong, Peter Öhman, Serge A Jabbour
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce glycaemia and weight, and improve cardiovascular risk factors via different mechanisms. We aimed to compare the efficacy and safety of co-initiation of the GLP-1 receptor agonist exenatide and the SGLT2 inhibitor dapagliflozin with exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled by metformin. METHODS: DURATION-8 was a 28 week, multicentre, double-blind, randomised, active-controlled phase 3 trial done at 109 sites in six countries...
December 2016: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/27633289/can-glucagon-like-peptide-1-glp1-agonists-or-sodium-glucose-co-transporter-2-sglt2-inhibitors-ameliorate-non-alcoholic-steatohepatitis-in-people-with-or-without-diabetes
#17
Vasilios G Athyros, Niki Katsiki, Asterios Karagiannis
No abstract text is available yet for this article.
September 9, 2016: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/27568470/mechanisms-of-improved-glucose-handling-after-metabolic-surgery-the-big-6
#18
REVIEW
Rebecca L Paszkiewicz, Richard N Bergman
For some time, it has been clear that elevated glucose is detrimental to the organism. A plethora of medicines have been introduced to reduce the fasting and postprandial glucose levels (including insulin, glucagon-like peptide receptor 1 [GLP-1] agonists, and sodium-glucose co-transporter 2 [SGLT2] inhibitors, among others). Although these medications are useful to reduce tissue exposure to glucose, no single compound and no combination have been able to totally normalize the blood sugar. Thus, it was astonishing when it was reported that surgery of the gastrointestinal tract could not only reduce obesity but also normalize the blood sugar...
July 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/27535321/dapagliflozin-stimulates-glucagon-secretion-at-high-glucose-experiments-and-mathematical-simulations-of-human-a-cells
#19
Morten Gram Pedersen, Ingela Ahlstedt, Mickaël F El Hachmane, Sven O Göpel
Glucagon is one of the main regulators of blood glucose levels and dysfunctional stimulus secretion coupling in pancreatic A-cells is believed to be an important factor during development of diabetes. However, regulation of glucagon secretion is poorly understood. Recently it has been shown that Na(+)/glucose co-transporter (SGLT) inhibitors used for the treatment of diabetes increase glucagon levels in man. Here, we show experimentally that the SGLT2 inhibitor dapagliflozin increases glucagon secretion at high glucose levels both in human and mouse islets, but has little effect at low glucose concentrations...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27440828/positioning-sglt2-inhibitors-incretin-based-therapies-in-the-treatment-algorithm
#20
REVIEW
John P H Wilding, Surya Panicker Rajeev, Ralph A DeFronzo
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are the most recent addition to the therapeutic options available for the treatment of type 2 diabetes and became available after the introduction of incretin-based therapies, dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs). These agents have potential advantages with regard to their weight loss-promoting effect, low risk of hypoglycemia, reduction in blood pressure, and reduction in cardiovascular events in high-risk patients (with empagliflozin)...
August 2016: Diabetes Care
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