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Diabetes, Obesity & Metabolism

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https://www.readbyqxmd.com/read/28432752/incretin-based-glucose-lowering-medications-and-the-risk-for-acute-pancreatitis-and-or-pancreatic-cancer-risk-reassuring-data-from-cardio-vascular-outcome-trials
#1
Michael A Nauck, Juris J Meier, Wolfgang E Schmidt
Incretin-based medications (glucagon-like peptide-1 [GLP-1] receptor agonists and inhibitors of dipeptidyl peptidase-4 [DPP-4] are glucose-lowering drugs approved and introduced after 2006 (1). Although both classes of drugs appeared to be relatively safe based on results from clinical trials and standard animal toxicology studies, epidemiological data (2, 3) and histological findings (4) in genetically modified rodents exposed to such agents have raised concern that pancreatitis and pancreatic cancer may be long-term risks associated with this therapy...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432746/impact-of-baseline-hba1c-diabetes-duration-and-bmi-on-clinical-outcomes-in-the-lixilan-o-trial-testing-iglarlixi-insulin-glargine-lixisenatide-titratable-fixed-ratio-combination-versus-insulin-glargine-and-lixisenatide-monocomponents
#2
M J Davies, L A Leiter, B Guerci, G Grunberger, F J Ampudia-Blasco, C Yu, W Stager, E Niemoeller, E Souhami, J Rosenstock
To determine whether baseline characteristics impact clinical outcomes in the LixiLan-O trial (N = 1170), the efficacy and safety of iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U (iGlar) and lixisenatide (Lixi) was compared with iGlar or Lixi alone in patients with uncontrolled type 2 diabetes mellitus (T2DM) on oral therapy. Subgroups according to baseline glycated haemoglobin (HbA1c; <8%, ≥8% [<64, ≥64 mmol/mol]); T2DM disease duration (<7, ≥7 years) and body mass index (BMI; <30, ≥30 kg/m(2) ) were investigated...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432745/safety-of-sitagliptin-in-patients-with-type-2-diabetes-and-chronic-kidney-disease-outcomes-from-tecos
#3
Samuel S Engel, Shailaja Suryawanshi, Susanna R Stevens, Robert G Josse, Jan H Cornel, Neli Jakuboniene, Axel Riefflin, Tsvetalina Tankova, Julio Wainstein, Eric D Peterson, Rury R Holman
AIMS: To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). MATERIALS AND METHODS: For participants with baseline eGFR measurements (n = 14,528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR <60 mL/min per 1.73 m(2) ) versus those without CKD. Within the CKD cohort, the same analyses were performed comparing sitagliptin- and placebo-assigned participants...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432726/combination-therapy-with-glp-1-receptor-agonist-and-sglt2-inhibitor
#4
REVIEW
Ralph A DeFronzo
The SGLT2 inhibitors (SGLTi) and glucagon-like-1 receptor agonists (GLP-1 RAs) effectively reduce HbA1c, but via very different mechanisms, making them an effective duet for combination therapy. Recently, drugs in both of these antidiabetic classes have been shown to reduce cardiovascular events, most likely by different mechanisms. SGLT2i appear to exert their CV protective actions by hemodynamic effects, while GLP-1 RAs work via anti-atherogenic/anti-inflammatory mechanisms, raising the possibility that combined therapy with these two classes may produce additive CV benefits...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432754/intraclass-differences-in-the-risk-of-hospitalisazion-for-heart-failure-among-type-2-diabetic-patients-initiating-a-dipeptydil-peptidase-4-inhibitor-or-a-sulphonylurea-results-from-the-osmed-health-db-registry
#5
Gian Paolo Fadini, Stefania Saragoni, Pierluigi Russo, Luca Degli Esposti, Saula Vigili de Kreutzenberg, Mario Melazzini, Angelo Avogaro
AIMS: Heart failure (HF) is frequent in type 2 diabetes (T2D) and several glucose-lowering medications may increase HF risk. In the SAVOR-TIMI trial, patients on Saxagliptin experienced a 27% higher risk of hospitalisation for HF (HHF). In a retrospective study on 127,555 patients, we showed that DPP-4i therapy was associated with a lower HHF risk than sulphonylurea (SU) therapy. We herein re-analyzed such data to evaluate intraclass differences among DPP-4i and SU. MATERIALS AND METHODS: We included T2D patients initiating DPP-4i or SU alone or in combination with metformin...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432751/acute-kidney-injury-plasma-lactate-concentrations-and-lactic-acidosis-in-metformin-users-a-godarts-study
#6
Paul J Connelly, Mike Lonergan, Enrique Soto-Pedre, Louise Donnelly, Kaixin Zhou, Ewan R Pearson
AIMS: Metformin is renally excreted and has been associated with the development of lactic acidosis. Although current advice is to omit metformin during illnesses that may increase risk of acute kidney injury (AKI), the evidence supporting this is lacking. We investigated the relationship between AKI, lactate concentrations and the risk of lactic acidosis in those exposed to metformin. METHODS: We undertook a population-based case-control study of lactic acidosis in 1,746 participants with Type 2 diabetes and 846 individuals without diabetes with clinically measured lactates with and without AKI between 1994-2014...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432748/future-challenges-and-therapeutic-opportunities-in-type-2-diabetes-changing-the-paradigm-of-current-therapy
#7
REVIEW
D R Owens, L Monnier, A H Barnett
Most algorithms for type 2 diabetes mellitus (T2DM) do not recommend treatment escalation until glycated haemoglobin (HbA1c) fails to reach the recommended target of 7% (53 mmol/mol) within approximately 3 months on any treatment regimen ('treat to failure'). Clinical inertia and/or poor adherence to therapy contribute to patients not reaching glycaemic targets when managed according to this paradigm. Clinical inertia exists across the entire spectrum of anti-diabetes therapies, although it is most pronounced when initiating and optimizing insulin therapy...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432733/variability-in-hba1c-blood-pressure-lipid-parameters-and-serum-uric-acid-and-risk-of-development-of-chronic-kidney-disease-in-type-2-diabetes
#8
Antonio Ceriello, Salvatore De Cosmo, Maria Chiara Rossi, Giuseppe Lucisano, Stefano Genovese, Roberto Pontremoli, Paola Fioretto, Carlo Giorda, Antonio Pacilli, Francesca Viazzi, Giuseppina Russo, Antonio Nicolucci
AIMS: Variability in HbA1c and blood pressure (BP) is associated with the risk of diabetic kidney disease (DKD). No evidence exists on the role of variability in lipids or serum uric acid (UA), or the interplay between the variability of different parameters, on renal outcomes. MATERIALS AND METHODS: Within the AMD Annals database we identified patients with ≥5 measurements of HbA1c, SBP and DBP, total-, HDL- and LDL- cholesterol, triglycerides, and UA. Patients were followed-up for up to 5 years...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28417575/effect-of-weight-reduction-on-hemoglobin-a1c-in-weight-loss-trials-of-type-2-diabetes-patients
#9
Anders Gummesson, Elisabeth Nyman, Mikael Knutsson, Martin Karpefors
AIMS: To quantify the effect of weight loss on HbA1c at group level based on data from published weight loss trials in overweight and obese type 2 diabetes patients. METHODS: A systematic literature search in MEDLINE, EMBASE and Cochrane CENTRAL (January 1990 through December 2012) was conducted to identify prospective trials of energy-reduced diets, obesity drugs or bariatric surgery conducted in adult, overweight and obese T2D patients. Based on clinical data from 3 to 24 months of follow-up, a linear model was developed to describe the effect of weight reduction on HbA1c...
April 18, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28419670/sglt2-and-sglt1-renal-expression-in-patients-with-type-2-diabetes
#10
Anna Solini, Chiara Rossi, Chiara Maria Mazzanti, Agnese Proietti, Hermann Koepsell, Ele Ferrannini
AIMS: The notion of an increased expression of SGLT2 in the kidney of patients with type 2 diabetes (T2DM) is based on a single ex vivo study of tubular cells harvested from the urine. DESIGN AND METHODS: We measured SGLT2 and SGLT1 expression in unaffected renal tissue from 19 T2DM patients and 20 age- and eGFR-matched nondiabetic subjects (CT) undergoing unilateral nephrectomy. Expression of SGLT2 and SGLT1 - and their cognate basolateral transporters GLUT2 and GLUT1 - was quantified by real-time and digital PCR; an affinity-purified antibody against human SGLT2 was used localize SGLT2 by immunohistochemistry...
April 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28417535/rates-of-hypoglycaemia-are-lower-in-patients-treated-with-insulin-degludec-liraglutide-ideglira-than-with-ideg-or-insulin-glargine-regardless-of-the-hypoglycaemia-definition-used
#11
P Norwood, R Chen, E Jaeckel, I Lingvay, H Jarlov, L Lehmann, S Heller
AIMS: The rates of hypoglycaemia reported in clinical trials are affected by the definitions of hypoglycaemia used. This post-hoc analysis took data from two trials comparing the once-daily, fixed ratio combination of insulin degludec/liraglutide (IDegLira) with basal insulin regimens, and re-analysed these data using alternative hypoglycaemia definitions and stratified outcomes by dosing time and baseline characteristics. MATERIALS AND METHODS: Post hoc analyses of the DUAL I (patients uncontrolled on oral antidiabetic drugs) and DUAL V (patients uncontrolled on insulin glargine (IGlar) U100) trials were carried out using different definitions of hypoglycaemia and by whether treatments were administered in the AM or PM...
April 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28417532/non-alcoholic-fatty-liver-disease-nafld-prevalence-and-its-metabolic-associations-in-patients-with-type-1-diabetes-and-type-2-diabetes
#12
Kenneth Cusi, Arun J Sanyal, Shuyu Zhang, Mark L Hartman, Juliana M Bue-Valleskey, Byron J Hoogwerf, Axel Haupt
We investigated non-alcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes (T1D), and in insulin-naïve and insulin-treated patients with type 2 diabetes (T2D). Baseline data from patients who had liver fat content (LFC) evaluated by magnetic resonance imaging in 4 phase 3 studies of basal insulin peglispro (BIL) were analyzed. Associations of NAFLD with clinical characteristics, glycemic control and diabetes therapy were evaluated. The prevalence of NAFLD (defined as LFC ≥6%) was low in T1D (8...
April 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28417527/effects-of-dapagliflozin-on-insulin-requirement-glucose-excretion-and-%C3%A3-hydroxybutyrate-levels-are-not-related-to-baseline-hba1c-in-youth-with-type-1-diabetes
#13
Torben Biester, Baerbel Aschemeier, Maryam Fath, Marcel Frey, Markus F Scheerer, Olga Kordonouri, Thomas Danne
Youth with type 1 diabetes (T1D) infrequently achieve HbA1c targets. Therefore, this placebo-controlled, randomized, crossover study was set up to assess the safety, effect and pharmacokinetics of a single dose of 10 mg dapagliflozin (DAPA) as add-on to insulin in relationship to HbA1c in youth. 33 youths (14 males, median age 16 years, diabetes duration 8 years) were included and stratified into three baseline HbA1c categories (<7.5%, 7.5 to 9.0% or >9.0; n = 11 each). During the study period of 24 hours, intravenous insulin administration and glucose-infusion kept blood glucose levels between 160-220 mg/dl...
April 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28417525/metformin-associated-lactic-acidosis-mala-moving-towards-a-new-paradigm
#14
REVIEW
Jean-Daniel Lalau, Farshad Kajbaf, Alessandro Protti, Mette Marie Christensen, Marc-Etienne De Broe, Nicolas Wiernsperger
Although metformin has been used for over 60 years, the balance between the drug's beneficial and adverse effects is still subject to debate. Following an analysis of how cases of so-called "metformin-associated lactic acidosis" (MALA) are reported in the literature, the present article reviews the pitfalls to be avoided when assessing the purported association between metformin and lactic acidosis. By starting from pathophysiological considerations, we propose a new paradigm for lactic acidosis in metformin-treated patients...
April 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28407415/impact-of-insulin-glargine-and-lixisenatide-on-beta-cell-function-in-patients-with-type-2-diabetes-mellitus-a-randomized-open-label-study
#15
Juris J Meier, Nina Schenker, Melanie Kahle, Freimut Schliess, Christoph Kapitza, Bjoern A Menge
Beta-cell function can be enhanced by direct stimulation of insulin secretion or by induction of beta-cell rest. Whether both strategies can complement each other has not yet been examined. 28 subjects with type 2 diabetes (HbA1c 7.8 ± 0.5 %) were treated with either lixisenatide or titrated insulin glargine, followed by their combined administration each over four weeks. First and second phase insulin secretion during an i.v. glucose challenge were calculated. First- and second-phase insulin secretion were not increased with glargine alone, but increased after addition of lixisenatide (p < 0...
April 13, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28407414/association-of-glucagon-like-peptide-1-receptor-agonist-glp-1-ra-use-and-rates-of-acute-myocardial-infarction-stroke-and-overall-mortality-in-patients-with-type-2-diabetes-mellitus-in-a-large-integrated-health-system
#16
Robert S Zimmerman, Todd M Hobbs, Brian J Wells, Sheldon X Kong, Michael W Kattan, Jon Bouchard, Kevin M Chagin, Changhong Yu, Brian Sakurada, Alex Milinovich, Wayne Weng, Janine M Bauman, Kevin M Pantalone
AIMS: To assess the potential impact of GLP-1 RA exposure on cardiovascular disease (CVD) and mortality outcomes in patients with type 2 diabetes (T2D), using a large retrospective cohort. MATERIALS AND METHODS: Patients with T2D between 2005-2014 (N = 105,862) were identified in the electronic health record system at Cleveland Clinic using a validated electronic phenotype. A time-dependent, Cox, multiple regression analysis was used to assess the association between GLP-1 RA exposure and risk of acute myocardial infarction (AMI), stroke/cerebrovascular accident (CVA), and overall mortality, as well as the composite of all three outcomes...
April 13, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28407342/cardiovascular-safety-of-insulin-between-real-world-data-and-reality
#17
EDITORIAL
Edoardo Mannucci, Ele Ferrannini
Over the last few years, the literature has been flooded with retrospective observational studies purporting to show that insulin treatment in patients with type 2 diabetes is associated with an increased risk of cardiovascular (CVD) morbidity and mortality in comparison with patients treated with non-insulin drugs(1-5) .
April 13, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28387052/examining-trends-in-type-2-diabetes-incidence-prevalence-and-mortality-in-the-uk-between-2004-and-2014
#18
Salwa S Zghebi, Douglas T Steinke, Matthew J Carr, Martin K Rutter, Richard A Emsley, Darren M Ashcroft
AIMS: Contemporary data describing type 2 diabetes prevalence, incidence and mortality are limited. We aimed to (i) estimate annual incidence and prevalence rates of type 2 diabetes in the UK between 2004 and 2014; (ii) examine relationships between observed rates with age, gender, socio-economic status and geographic region; and (iii) assess how temporal changes in incidence and all-cause mortality rates influence changes in prevalence. METHODS: Type 2 diabetes cases aged ≥16 years between January 2004 and December 2014 were identified using the Clinical Practice Research Datalink (CPRD)...
April 7, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28387058/impact-of-empagliflozin-on-blood-pressure-in-dipper-and-non-dipper-patients-with-type-2-diabetes-mellitus-and-hypertension
#19
Robert Chilton, Ilkka Tikkanen, Uwe Hehnke, Hans J Woerle, Odd Erik Johansen
In the EMPA-REG BP® trial, empagliflozin significantly reduced systolic and diastolic blood pressure (SBP and DBP) versus placebo at week 12 in patients with type 2 diabetes mellitus (T2DM) and hypertension. In a post-hoc analysis, we assessed the effect of empagliflozin on SBP and DBP using 24-hour ambulatory BP monitoring in patients categorized as dippers (sleep-time mean SBP ≤90% of awake-time mean; n = 417) or non-dippers (sleep-time mean SBP >90% of awake-time mean; n = 350). In dippers, adjusted mean (SE) changes from baseline in mean 24-hour SBP (mmHg) at week 12 were -0...
April 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28386990/consistent-findings-in-glycaemic-control-body-weight-and-hypoglycaemia-with-iglarlixi-insulin-glargine-lixisenatide-titratable-fixed-ratio-combination-versus-insulin-glargine-across-baseline-hba1c-bmi-and-diabetes-duration-categories-in-the-lixilan-l-trial
#20
C Wysham, R C Bonadonna, V R Aroda, M Puig-Domingo, C Kapitza, W Stager, C Yu, E Niemoeller, E Souhami, R M Bergenstal
AIM: To assess the impact of baseline characteristics on clinical outcomes in the LixiLan-L trial, a randomized open-label trial designed to evaluate the efficacy and safety of iGlarLixi, a novel fixed-ratio combination of insulin glargine 100 U (iGlar) plus lixisenatide, in comparison with iGlar over 30 weeks in a population of patients with type 2 diabetes mellitus (T2DM) inadequately controlled on a previous regimen of basal insulin alone or in combination with one or two oral glucose-lowering drugs...
April 6, 2017: Diabetes, Obesity & Metabolism
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