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https://www.readbyqxmd.com/read/29449146/efficacy-and-safety-of-combination-therapy-with-sglt2-and-dpp4-inhibitors-in-the-treatment-of-type-2-diabetes-a-systematic-review-and-meta-analysis
#1
Y K Cho, Y M Kang, S E Lee, J Lee, J-Y Park, W J Lee, Y-J Kim, C H Jung
BACKGROUND: This review evaluated the efficacy and safety of a combination therapy comprising a sodium-glucose cotransporter type 2 inhibitor (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP4i) in type 2 diabetes. METHODS: A literature search through to May 2017 was carried out of PubMed, Embase and the Cochrane Central Register of Controlled Trials. Studies were eligible if they were randomized controlled trials (RCTs) comparing SGLT2i plus DPP4i (SGLT2i/DPP4i) against DPP4i±placebo or SGLT2i±placebo and published in English...
February 3, 2018: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29371333/mechanisms-in-endocrinology-sglt2-inhibitors-clinical-benefits-by-restoration-of-normal-diurnal-metabolism
#2
Russell L Esterline, Allan Vaag, Jan Oscarsson, Jiten Vora
Type 2 diabetes (T2D) is associated with inhibition of autophagic and lysosomal housekeeping processes that detrimentally affect key organ functioning; a process likely to be exacerbated by conventional insulin-driven anabolic therapies. We propose that the cardio-renal benefits demonstrated with sodium-glucose cotransporter-2 inhibitor (SGLT2i) treatment in T2D partly may be explained by their ability to drive consistent, overnight periods of increased catabolism brought about by constant glucosuria. Key steps driving this catabolic mechanism include: a raised glucagon/insulin ratio initially depleting glycogen in the liver and ultimately activating gluconeogenesis utilizing circulating amino acids (AAs); a general fuel switch from glucose to free fatty acids (accompanied by a change in mitochondrial morphology from a fission to a sustained fusion state driven by a decrease in AA levels); a decrease in circulating AAs and insulin driving inhibition of mammalian target of rapamycin complex 1 (mTORC1), which enhances autophagy/lysosomal degradation of dysfunctional organelles, eventually causing a change in mitochondrial morphology from a fission to a sustained fusion state...
January 25, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29334278/a-comparative-safety-review-between-glp-1-receptor-agonists-and-sglt2-inhibitors-for-diabetes-treatment
#3
Agostino Consoli, Gloria Formoso, Maria Pompea Antonia Baldassarre, Fabrizio Febo
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...
January 15, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29322486/dapagliflozin-and-empagliflozin-ameliorate-hepatic-dysfunction-among-chinese-subjects-with-diabetes-in-part-through-glycemic-improvement-a-single-center-retrospective-observational-study
#4
Paul Chi Ho Lee, Yunjuan Gu, Man Yi Yeung, Carol Ho Yi Fong, Yu Cho Woo, Wing Sun Chow, Kathryn Tan, Karen Siu Ling Lam
INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve hepatic dysfunction, although studies focusing on their underlying mechanisms are lacking, especially ones on dapagliflozin and empagliflozin. Here, we investigated the relationship between amelioration of hepatic dysfunction and improvement in various metabolic parameters among Chinese subjects with type 2 diabetes (T2DM). METHODS: This was a single-center, retrospective, observational study that involved 115 Chinese participants with T2DM treated with either dapagliflozin or empagliflozin for at least 6 months between July 2016 and February 2017...
January 10, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29322280/direct-cardiovascular-impact-of-sglt2-inhibitors-mechanisms-and-effects
#5
REVIEW
Abdullah Kaplan, Emna Abidi, Ahmed El-Yazbi, Ali Eid, George W Booz, Fouad A Zouein
Diabetes is a global epidemic and a leading cause of death with more than 422 million patients worldwide out of whom around 392 million alone suffer from type 2 diabetes (T2D). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel and effective drugs in managing glycemia of T2D patients. These inhibitors gained recent clinical and basic research attention due to their clinically observed cardiovascular protective effects. Although interest in the study of various SGLT isoforms and the effect of their inhibition on cardiovascular function extends over the past 20 years, an explanation of the effects observed clinically based on available experimental data is not forthcoming...
January 11, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29285458/sodium-glucose-cotransporter-2-inhibitors-moving-beyond-the-glycemic-treatment-goal
#6
REVIEW
Vishal Gupta, William Canovatchel, B N Lokesh, Ravi Santani, Nishant Garodia
Revelations of the multifactorial pathogenesis of type 2 diabetes mellitus (T2DM) that extend beyond the role of insulin and glucose utilization have been crucial in redefining the treatment paradigm. The focus of treatment is currently directed towards achieving wide-ranging targets encompassing the management of cardiovascular comorbidities that have been evidenced as indispensable aspects of T2DM. While most currently prescribed antihyperglycemic agents have little or no effect on reducing cardiovascular risks, some have been associated with undesirable effects on common risk factors such as weight gain and cardiovascular sequelae...
November 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29241389/euglycemic-diabetic-ketoacidosis-associated-with-sodium-glucose-cotransporter-type-2-inhibitors-in-patients-with-type-2-diabetes-mellitus-receiving-oral-therapy
#7
Ryan B Dull, Mikayla L Spangler, Emily L Knezevich, Britney M Lau
INTRODUCTION AND OBJECTIVE: Postmarketing reports and warnings of serious adverse events such as diabetic ketoacidosis (DKA) have raised concern regarding the safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i). This report describes 2 cases of symptomatic SGLT2i-associated euglycemic DKA (euDKA) leading to hospitalization in patients with type 2 diabetes mellitus (DM) previously well controlled on oral medications. CASE REPORTS: Subject 1 is a 55-year-old female admitted with euDKA precipitated by infection and managed with intravenous insulin...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/29241374/pharmacokinetic-drug-evaluation-of-empagliflozin-plus-linagliptin-for-the-treatment-of-type-2-diabetes
#8
Christos V Rizos, Theodosios D Filippatos, Moses S Elisaf
Type 2 diabetes mellitus has become a growing epidemic and therefore efficient treatment strategies that target its management are needed. The treatment of diabetic patients often requires the combination of antidiabetic drug classes. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) block glucose reabsorption in the proximal renal tubules. Dipeptidyl peptidase-4 inhibitors (DPP-4i) improve glucose metabolism by blocking the enzyme that degrades incretins leading to increased insulin secretion. Areas covered: The aim of the review is to present the available data on pharmacokinetic properties/pharmacodynamics, metabolic and cardiovascular effects of empagliflozin plus linagliptin combination...
December 19, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29226041/dapagliflozin-cardiovascular-safety-and-benefits-in-type-2-diabetes-mellitus
#9
REVIEW
Fatima Saleem
Sodium-glucose co-transporter 2 inhibitors (SGLT2is) such as dapagliflozin, canagliflozin, and empagliflozin, are a promising new therapy in the treatment of type 2 diabetes mellitus (T2DM). SGLT2is can effectively reduce hyperglycemia thus improving glycemic control and they offer some beneficial effects on the cardiovascular (CV) system which can benefit patients with heart failure in addition toT2DM. The United States Food and Drug Administration requires new diabetes mellitus therapies to show a CV safety profile...
October 5, 2017: Curēus
https://www.readbyqxmd.com/read/29225209/dapagliflozin-reduces-fat-mass-without-affecting-muscle-mass-in-type-2-diabetes
#10
Seigo Sugiyama, Hideaki Jinnouchi, Noboru Kurinami, Kunio Hieshima, Akira Yoshida, Katsunori Jinnouchi, Hiroyuki Nishimura, Tomoko Suzuki, Fumio Miyamoto, Keizo Kajiwara, Tomio Jinnouchi
AIM: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) therapy has been demonstrated to improve glycemic control and reduce body weight and fat mass in type 2 diabetes mellitus (T2DM). Here, our aim was to investigate the effects of SGLT2i dapagliflozin-treatment on body muscle mass and muscle fat content in patients with T2DM. METHODS: We prospectively recruited uncontrolled (hemoglobin A1c [HbA1c] >7%) Japanese T2DM patients who had a body mass index (BMI) <35 kg/m2...
December 8, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/29215196/comparison-between-sglt2-inhibitors-and-pioglitazone-as-additions-to-insulin-therapy-in-type-2-diabetes-a-systematic-review-with-an-indirect-comparison-meta-analysis
#11
Yun Kyung Cho, Ye-Jee Kim, Yu Mi Kang, Seung Eun Lee, Joong-Yeol Park, Woo Je Lee, Chang Hee Jung
AIMS/INTRODUCTION: We aimed to evaluate the efficacy and safety of pioglitazone (PIO) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) as additions to insulin therapy for the management of type 2 diabetes mellitus (T2D). MATERIALS AND METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials. gov through December 2016. Randomized controlled trials (RCTs) published in English that compared SGLT2i plus insulin (SGLT2i/INS) or PIO plus insulin (PIO/INS) with placebo plus insulin (PCB/INS) in T2D patients were included...
December 7, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29213337/effectiveness-of-long-term-treatment-with-sglt2-inhibitors-real-world-evidence-from-a-specialized-diabetes-center
#12
Yotsapon Thewjitcharoen, Nalin Yenseung, Areeya Malidaeng, Soontaree Nakasatien, Phawinpon Chotwanvirat, Sirinate Krittiyawong, Ekgaluck Wanothayaroj, Thep Himathongkam
Background: Diabetes is a progressive disease needing multiple drugs for achieving and maintaining good glycemic control. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) is a novel class of anti-diabetic agent which offers several beneficial effects. However, the long-term effectiveness in clinical practice and safety data of SGLT2 inhibitors is limited, especially in Asian patients. To better understand the effectiveness of SGLT2i in clinical practice, we conducted a retrospective evaluation of patients with diabetes on SGLT2i...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/29197997/class-effects-of-sglt2-inhibitors-in-mouse-cardiomyocytes-and-hearts-inhibition-of-na-h-exchanger-lowering-of-cytosolic-na-and-vasodilation
#13
Laween Uthman, Antonius Baartscheer, Boris Bleijlevens, Cees A Schumacher, Jan W T Fiolet, Anneke Koeman, Milena Jancev, Markus W Hollmann, Nina C Weber, Ruben Coronel, Coert J Zuurbier
AIMS/HYPOTHESIS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) constitute a novel class of glucose-lowering (type 2) kidney-targeted agents. We recently reported that the SGLT2i empagliflozin (EMPA) reduced cardiac cytosolic Na+ ([Na+]c) and cytosolic Ca2+ ([Ca2+]c) concentrations through inhibition of Na+/H+ exchanger (NHE). Here, we examine (1) whether the SGLT2i dapagliflozin (DAPA) and canagliflozin (CANA) also inhibit NHE and reduce [Na+]c; (2) a structural model for the interaction of SGLT2i to NHE; (3) to what extent SGLT2i affect the haemodynamic and metabolic performance of isolated hearts of healthy mice...
December 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/29193543/initiation-of-dapagliflozin-and-treatment-emergent-fractures
#14
Konstantinos A Toulis, John P Bilezikian, G Neil Thomas, Wasim Hanif, Kalliopi Kotsa, Rasiah Thayakaran, Deepiksana Keerthy, Abd Tahrani, Krishnarajah Nirantharakumar
An increase in the fracture risk was reported in patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin, possibly mediated by effects induced by all members of the sodium-glucose co-transporter 2 inhibitors (SGLT2i) class. It is unclear whether initiation of dapagliflozin is followed by an increase in the risk of fracture. Therefore, we performed a population-based, open cohort study was performed (January 2013-January 2016) using The Health Improvement Network (THIN). 22,618 patients with T2DM (4,548 exposed to dapagliflozin and 18,070 under standard antidiabetic treatment, matched for age and sex) with no history of fractures at baseline...
November 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29183654/-safety-of-sglt2-inhibitors-a-review-of-the-adverse-drug-reactions-registered-in-a-national-database
#15
O Esteban-Jiménez, C Navarro-Pemán, L Urieta-González
OBJECTIVE: To analyse the adverse drug reactions (ADRs) caused by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) notified in Spain since they have been on the market. MATERIAL AND METHODS: An analysis was made of all the notifications registered in the Spanish Pharmacovigilance System of drugs for human use, arising from the use of SGLT2i. RESULTS: A total of 311 notifications were recorded, of which 169 (54.34%) were related to dapagliflozin, 81 (26...
November 25, 2017: Semergen
https://www.readbyqxmd.com/read/29174215/choosing-dipeptidyl-peptidase-4-inhibitors-sodium-glucose-cotransporter-2-inhibitors-or-both-as-add-ons-to-metformin-patient-baseline-characteristics-are-crucial
#16
Ronald M Goldenberg
PURPOSE: Type 2 diabetes remains a poorly managed disease, with only about half of individuals with type 2 diabetes meeting guideline-recommended glycosylated hemoglobin (HbA1C) targets. A major proportion of those who have not met HbA1C goals have an HbA1C <8.0% to 8.5%. In practice, it is quite common to have to decide between dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) as add-ons to metformin to help these individuals meet their HbA1C goals...
November 22, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/29168157/perioperative-implications-of-sodium-glucose-cotransporter-2-inhibitors-a-case-series-of-euglycemic-diabetic-ketoacidosis-in-three-patients-after-cardiac-surgery
#17
Aaron Lau, Simon Bruce, Erica Wang, Ron Ree, Kevin Rondi, Anthony Chau
PURPOSE: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) comprise the newest class of oral hypoglycemic agents approved for treating type II diabetes mellitus (DM-II). Their use, however, has been associated with the rare development of euglycemic diabetic ketoacidosis (euDKA). We present three cases of euDKA that occurred following elective coronary artery bypass grafting surgery. The role of the anesthesiologist in the prevention, diagnosis, and management of this complication is also discussed...
November 22, 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/29162781/successful-withdrawal-from-dobutamine-by-canagliflozin-in-a-diabetic-patient-with-stage-d-heart-failure
#18
Masaki Nakagaito, Shuji Joho, Ryuichi Ushijima, Makiko Nakamura, Tadakazu Hirai, Koichiro Kinugawa
Patients with stage D heart failure (HF) frequently become dependent on high doses of diuretics and inotropic agents. Recently, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), an oral antidiabetic agent, has been demonstrated to have favorable effects in preventing HF. However, it remains unknown whether SGLT2i is reliable for patients with decompensated HF. We experienced a case of a patient with stage D HF for whom attempting intravenous dobutamine withdrawal was difficult even after the administration of all conventional pharmacological treatment...
November 22, 2017: International Heart Journal
https://www.readbyqxmd.com/read/29162514/increased-sugar-intake-as-a-form-of-compensatory-hyperphagia-in-patients-with-type-2-diabetes-under-dapagliflozin-treatment
#19
Ichiro Horie, Norio Abiru, Ryoko Hongo, Takeshi Nakamura, Ayako Ito, Ai Haraguchi, Shoko Natsuda, Ikuko Sagara, Takao Ando, Atsushi Kawakami
AIMS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) cause substantially less weight loss than would be expected based on their caloric deficits, probably due to enhanced appetite regulation known as "compensatory hyperphagia," which occurs to offset the negative energy balance caused by increased glycosuria. We examined whether any specific nutrients contributed to the compensatory hyperphagia in diabetic patients taking SGLT2i. METHODS: Sixteen patients with type 2 diabetes were newly administered dapagliflozin 5 mg daily as the experimental SGLT2i group...
November 18, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29144539/model-based-evaluation-of-proximal-sodium-reabsorption-through-sglt2-in-health-and-diabetes-and-the-effect-of-inhibition-with-canagliflozin
#20
Jessica A Brady, K Melissa Hallow
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce glucose levels in diabetes by inhibiting renal glucose reabsorption in the proximal tubule (PT), resulting in urinary glucose excretion. A recent large cardiovascular outcomes trial suggested that the SGLT2i empagliflozin may also decrease risk of renal dysfunction. Because sodium (Na) and glucose reabsorption are coupled through SGLT2, it is hypothesized that the renal benefits may be derived from lowering Na reabsorption in the PT, which would lead to favorable renal hemodynamic changes...
November 16, 2017: Journal of Clinical Pharmacology
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