Journal of Diabetes News
2015; Wiley; Volume: 7; Issue: 5 Linguagem: Inglês
10.1111/1753-0407.12315
ISSN1753-0393
Tópico(s)Gut microbiota and health
ResumoJournal of DiabetesVolume 7, Issue 5 p. 595-598 Journal of Diabetes NewsFree Access Journal of Diabetes News First published: 19 May 2015 https://doi.org/10.1111/1753-0407.12315AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Emily E. Regier, Manu V. Venkat, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each quarter, the Journal of Diabetes includes this News feature, in which Regier, Venkat, and Close review the latest developments relevant to researchers and clinicians. 97th Annual Meeting of the Endocrine Society (ENDO 2015) ENDO 2015 took place 5–8 March 2015 in San Diego, CA, USA, attracting 8500 attendees from around the world. Dr Carol Wysham (Rockwood Center for Diabetes and Endocrinology, Spokane, WA, USA) presented results from a meta-analysis (15 randomized controlled trials; n = 4557) demonstrating improved glycemic control and beneficial effects on weight with glucagon-like peptide-1 (GLP-1) agonist/basal insulin combination therapy versus basal-bolus therapy or basal insulin alone. Results showed significantly greater HbA1c reductions with basal insulin/GLP-1 agonist combination therapy compared with insulin alone (difference in average reduction = 0.5%; P < 0.0001), as well as a higher percentage of patients achieving an HbA1c ≤7% (odds ratio [OR] 3.22; 95% confidence interval [CI] 1.99–5.19; P < 0.0001). The addition of a GLP-1 agonist also produced weight loss rather than weight gain (difference in means −3.09 kg; P < 0.0001), a result that was consistent across all studies. Rates of symptomatic hypoglycemia were comparable between the two groups (OR 1.08; 95% CI 0.75–1.56; P = 0.6893). However, patients in the GLP-1 agonist group were more likely to achieve a composite endpoint of an HbA1c ≤7% without weight gain or hypoglycemia (OR 6.05; 95% CI 2.55–14.37; P < 0.0001), although only four studies were included in that specific analysis. The conference featured two new analyses from the SCALE Phase 3 trial program for Novo Nordisk's (Bagsvaerd, Denmark) Saxenda (liraglutide 3.0 mg). Dr Ofri Mosenzon (Hadassah University Hospital, Jerusalem, Israel) presented a selective analysis of responders (those who achieved ≥5% weight loss from baseline at Week 56) from the Effect of Liraglutide on Body Weight in Overweight or Obese Subjects with Type 2 Diabetes (SCALE Diabetes) trial. The average weight loss was greater among responders (10.3%) relative to the full liraglutide 3.0 mg group (5.9%). A significantly higher percentage of those on liraglutide 3.0 mg (49.9%) were defined as responders compared with those on liraglutide 1.8 mg (35.6%) or placebo (13.8%). Within the liraglutide 3.0 mg group, responders experienced greater improvements in HbA1c (−1.6% vs −1.0%), fasting plasma glucose (FPG), systolic blood pressure (−5.0 vs −0.5 mmHg), and physical functioning (Impact of Weight on Quality of Life-Lite score improvements of 19.0 vs 11.1) compared with non-responders. There were no significant differences between responders and non-responders in terms of severe adverse events and hypoglycemic episodes (0.9 vs 0.8 events/patient year), although gastrointestinal adverse events were more frequent in responders than non-responders (76% vs 55%). Dr David Lau (University of Calgary, Calgary, Canada) presented hypoglycemia data from the Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects with Co-Morbidities (SCALE Obesity and Prediabetes) trial. Results demonstrated that clinically relevant hypoglycemia events, defined as plasma glucose ≤56 mg/dL, were rare regardless of how they were assessed: hypoglycemia ascertained via FPG tests during study visits had an incidence of 0.1% with liraglutide 3.0 mg versus 0% with placebo, and the incidence of hypoglycemia during oral glucose tolerance test (OGTT) sessions was 2.3% with liraglutide 3.0 mg compared with 0% with placebo. With hypoglycemia defined as plasma glucose ≤70 mg/dL, there were larger disparities, with the liraglutide 3.0 mg group experiencing more events compared with the placebo group: the incidence was 1.3% vs 1.0% for spontaneously reported events, 3.6% vs 0.8% for FPG measurements, and 8.3% vs 1.4% for OGTT measurements. No hypoglycemic events required third-party assistance. Of the events detected during FPG and OGTT visits, respectively, 31.3% and 41.5% with liraglutide 3.0 mg vs 30.0% and 33.0% with placebo were asymptomatic. Hypoglycemic events were less common in participants with prediabetes (9.4% with liraglutide 3.0 mg and 2.6% with placebo) compared with those who were normoglycemic (15.9% with liraglutide and 4.3% with placebo). Dr Riitta Veijola (University of Oulu, Oulu, Finland) presented data suggesting that HbA1c can be a useful predictive marker of the time to diagnosis of type 1 diabetes (T1D) in genetically predisposed children. The findings come from a recent study in Finland that identified children with multiple islet autoantibodies and collected HbA1c measurements from them regularly for approximately 5 years. In the 201 (43%) patients that progressed to T1D, the results indicated that deteriorating glucose metabolism, as assessed by HbA1c, could often predict the progression to T1D roughly 1 year out from diagnosis. Specifically, a 10% increase in HbA1c levels in samples taken 3–12 months apart predicted the diagnosis of clinical disease (hazard ratio [HR] 5.7) within a median time of 1.1 years, whereas an HbA1c ≥5.9% in two consecutive samples predicted diagnoses even more significantly (HR 11.9) with a median time to diagnosis of 0.9 years. Dr Marian Rewers (University of Colorado, Denver, CO, USA) shared preliminary data from The Environmental Determinants of Diabetes in the Young (TEDDY) study on the potential role of viruses and gut microbiota in T1D. The TEDDY investigators are currently conducting a case-control study comparing the microbial composition of stool and plasma samples from children with and without persistent autoantibodies (n = 41 in each group). So far, Dr Rewers reported that enteroviruses have been found in 29.3% of all stool samples studied, and certain viruses have been found only in cases and only in controls. The laboratory work is 90% complete, with data analysis to follow. Dr Rewers also mentioned findings from separate preliminary analyses suggesting that children in TEDDY with autoantibodies or overt T1D have greater gut bacterial diversity compared with controls; as he noted, this stands in direct contrast to findings from the largest study in this area published to date.1 He also referred briefly to TEDDY data suggesting that the use of probiotics in the first few months of life may be protective against T1D, although he stressed that larger, better-controlled studies are needed to draw more reliable conclusions. Reference 1Kostic AD, Gevers D, Siljander H et al. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe. 2015; 17: 260– 273. CrossrefCASPubMedWeb of Science®Google Scholar Company updates March 19: Sanofi (Paris, France) announced positive topline results from the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) cardiovascular outcomes trial for its GLP-1 agonist Lyxumia (lixisenatide). The trial met its primary endpoint of cardiovascular non-inferiority with Lyxumia compared with placebo using a composite of adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for unstable angina). Full results from the trial will be presented at the American Diabetes Association's 75th Scientific Sessions in June 2015. March 19: Biodel (Danbury, CT, USA) announced positive results from a Phase 1 proof-of-concept trial of its glucagon formulation BIOD-961 (for use in its Glucagon Emergency Management autoreconstitution rescue device). The randomized double-blind six-arm cross-over study enrolled 15 healthy volunteers (10 of whom completed the study) who received subcutaneous and intramuscular 1-mg doses of BIOD-961 and Lilly's (Indianapolis, IN, USA) and Novo Nordisk's (Bagsvaerd, Denmark) marketed glucagon formulations in a random sequence. There were no significant differences in time to peak concentration or area under the curve for either plasma glucagon or blood glucose with BIOD-961 compared with either comparator. March 26: Novo Nordisk announced topline results from the final two of four total Phase 3a trials for its faster-acting formulation of insulin aspart (Faster aspart). Both trials met their primary endpoint of HbA1c non-inferiority versus NovoLog (insulin aspart), with one trial finding modestly but significantly larger HbA1c reductions with Faster aspart taken at mealtime (−0.32%) compared with NovoLog taken at mealtime (−0.17%) after 26 weeks (mean baseline HbA1c = 7.6%). A third arm that received Faster aspart after mealtime had a non-inferior HbA1c reduction from baseline (−0.13%) compared with NovoLog taken at mealtime, although it did not match Faster aspart dosed at mealtime. In both trials, Faster aspart was associated with significantly reduced postprandial glucose excursions compared with NovoLog; the magnitude of the difference at 1 h post-meal was 11–18 mg in the two trials. April 1: The US Food and Drug Administration (FDA) announced the approval of Bayer (Leverkusen, Germany)/Regeneron's (Tarrytown, NY, USA) Eylea (intravitreal aflibercept) for diabetic retinopathy (DR) in patients with diabetic macular edema (DME). Eylea has been approved for DME without the DR indication since July 2014 and for wet age-related macular degeneration (wet AMD) since 2011. The approval was supported by 2-year results from the Phase 3 Study of Intravitreal Aflibercept Injection in Patients with Diabetic Macular Edema (VISTA DME) and Intravitreal Aflibercept Injection in Vision Impairment Due to DME (VIVID-DME) studies, which found significantly greater improvements in DR severity with Eylea versus macular laser photocoagulation. April 7: Biodel announced positive results from an initial human factors study of its Glucagon Emergency Management (GEM) autoreconstitution device for severe hypoglycemia. The study (n = 24) demonstrated significantly greater usability with the GEM device compared with Lilly's and Novo Nordisk's marketed glucagon rescue kits: 87% of participants successfully delivered a full dose of glucagon with the GEM device compared with 6% with the marketed kits, and the average time to dose delivery was 76 vs 113 s (P < 0.05). The success rate was comparable between trained and untrained participants. April 15: Mitsubishi Tanabe (Osaka, Japan) is sponsoring a Phase 3 study investigating the coadministration of Invokana (canagliflozin), which it originally developed and licensed to Johnson & Johnson (New Brunswick, NJ, USA), and its dipeptidyl peptidase (DPP)-4 inhibitor Tenelia (teneligliptin) in Japanese patients with type 2 diabetes (T2D). The double-blind trial will compare Invokana coadministered with Tenelia vs placebo coadministered with Tenelia in 140 patients with T2D. The primary endpoint is change in HbA1c from baseline after 24 weeks. Secondary endpoints include change in body weight, fasting plasma glucose, 0–2-h postprandial plasma glucose in range, and 2-h postprandial plasma glucose. Primary completion is expected in May 2016. April 27: Merck (White House Station, NJ, USA) announced positive topline results from the Trial to Evaluate Cardiovascular Outcomes after Treatment with Sitagliptin (TECOS), the cardiovascular outcomes trial for its DPP-4 inhibitor Januvia (sitagliptin). The trial met its primary endpoint of cardiovascular non-inferiority with Januvia compared with placebo using a composite of adverse cardiovascular events (cardiovascular-related death, non-fatal myocardial infarction, non-fatal stroke, or unstable angina requiring hospitalization). There was also no increase in hospitalization for heart failure with Januvia versus placebo. Full results from the trial will be presented at the American Diabetes Association's 75th Scientific Sessions in June 2015. April 27: MedImmune (Gaithersburg, MD, USA), AstraZeneca's (London, UK) biologics research arm is initiating a Phase 1 trial of a GLP-1/glucagon dual agonist (MEDI0382) for diabetes and obesity. The single-ascending-dose randomized double-blind placebo-controlled trial aims to evaluate the safety and tolerability of eight different doses of MEDI0382 (administered via subcutaneous injection) in 64 healthy volunteers; it includes several secondary endpoints related to pharmacokinetics. Primary completion is expected in August 2015. April 29: Lexicon (The Woodlands, TX, USA) announced that the first of two pivotal Phase 3 studies for its sodium–glucose cotransporter (SGLT)-1/SGLT-2 dual inhibitor sotagliflozin (LX4211) in T1D has commenced enrollment. The second pivotal trial is expected to begin screening patients soon. In addition, the company plans to conduct a larger Phase 3 study to accrue sufficient safety data. A Phase 2 study focused on younger adults with more poorly controlled T1D, conducted in collaboration with JDRF, is ongoing. May 4: Imperial College London (London, UK) is recruiting patients for a Phase 2 study that will evaluate the safety and efficacy of Novo Nordisk's (Bagsvaerd, Denmark) Victoza (liraglutide 1.8 mg) in Alzheimer's disease. The trial, Evaluating Liraglutide in Alzheimer's Disease (ELAD) has an estimated enrollment of 206 individuals aged 50–85 years with early stage Alzheimer's disease as defined by criteria of the National Institute of Neurological and Communicative Disorders and Stroke. Individuals with diabetes will be ineligible for the study. Participants will be randomized to receive daily injections of either liraglutide or placebo for 12 months. The primary endpoint is change in baseline cerebral glucose metabolic rate; secondary endpoints include changes in cognitive function, magnetic resonance imaging patterns, microglial activation, and cerebrospinal fluid markers. Primary completion is expected in January 2017. May 6: GlaxoSmithKline (London, UK) has initiated a Phase 2 trial of its GLP-1 agonist Tanzeum (albiglutide) in T1D. The randomized double-blind placebo-controlled 52-week multicenter study will have a primary endpoint of change in stimulated (from a mixed-meal tolerance test) plasma C-peptide area under the curve from baseline to 52 weeks. It is currently recruiting, with an estimated enrollment of 68 patients and an estimated primary completion date of December 2016. May 7: Biocon (Bangalore, India) announced that the first set of US clinical trials (through Phase 2a) for its oral insulin IN-105 completed in April 2015. In addition, the company announced that recruitment is complete in the global Phase 3 trial of its biosimilar insulin glargine formulation (partnered with Mylan [Canonsburg, PA, USA]) in T1D and that the T2D trial should be fully enrolled in July 2015. Both trials are expected to complete in June 2016. The insulin glargine formulation was also recently approved in Mexico, where it will be marketed in partnership with Pisa Farmacéutica under the trade name Galactus. Volume7, Issue5September 2015Pages 595-598 ReferencesRelatedInformation
Referência(s)