Canadian Journal of Diabetes

55 - Comparative Analysis of A1c and Weight Reduction Potential of Subcutaneous GLP-1 Receptor Agonists in a Real-World Setting


1 month 3 weeks ago

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are now routinely used in the management of type 2 diabetes due to their additional benefits beyond glycemic control. However, there is limited data on their efficacy in real clinical practice, and the purpose of this study is to compare the clinical efficacy of GLP-1 RAs by comparing A1c lowering and weight reduction between these agents.
Jeffery Tong, Akshay Jain, Sara Stafford

56 - Effect of Oral Semaglutide With or Without Background SGLT2i in Patients With T2D: Subgroup Analysis of PIONEER 4


1 month 3 weeks ago

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT2is) are widely used to treat type 2 diabetes (T2D), but trial data on their combined use are limited. We report the first data on oral semaglutide in combination with SGLT2i. This was a posthoc subgroup analysis of the 52-week, double-blind, double-dummy PIONEER 4 trial (NCT02863419), in which patients with T2D uncontrolled on metformin with or without SGLT2i were randomized 2:2:1 to once-daily oral semaglutide 14 mg, subcutaneous (s.c.) liraglutide 1.8 mg or placebo.
Ronald M. Goldenberg, Richard E. Pratley, Robert Bauer, Kamlesh Khunti, Eskil Kreiner, Peter Nørkjær Laursen, Juris J. Meier

57 - Efficacy and Safety of Oral Semaglutide by Baseline Age in the PIONEER Clinical Trial Program


1 month 3 weeks ago

In an exploratory analysis of 7 global phase 3a trials (PIONEER 1–5, 7 and 8), we evaluated the effect of age at baseline on efficacy (<45, ≥45 – <65 or ≥65 years) and safety (<65 or ≥65 years) for oral semaglutide (3, 7, 14 mg once daily) vs comparators in patients with type 2 diabetes. Efficacy endpoints: change from baseline in glycated hemoglobin (HbA1c) and body weight. Across all trials, there were 582, 3,392 and 1,683 patients aged <45, ≥45 – <65 and ≥65 years, respectively. Baseline HbA1c was similar across age groups, whereas baseline body weight tended to be higher in younger patients.
Sue Pedersen, Vanita R. Aroda, Robert Bauer, Christin Løth Hertz, Eduard Montanya, Mark L. Warren, Bertrand Cariou

58 - Efficacy of Oral Semaglutide According to Background Medication: An Exploratory Subgroup Analysis of the PIONEER Trial Program


1 month 3 weeks ago

The global PIONEER program investigated the efficacy and safety of the first oral glucagon-like peptide-1 receptor agonist, oral semaglutide. Across PIONEER trials, patients with type 2 diabetes (T2D) were randomized to once-daily oral semaglutide (3, 7, 14 mg or flexibly dosed) or comparator. The present exploratory subgroup analysis evaluated the effect of background medications on glycated hemoglobin (HbA1c) and body weight (BW) reductions at the end of trial (week 26, 52 or 78) in 5 PIONEER trials (3–5, 7–8).
Daniel Ngui, John Buse, Matthew Crowley, Jan W. Eriksson, Mette Gislum, Christin Løth Hertz, Marcel Kaiser, Anne Møller Nielsen, Martin Haluzík

59 - Greater Reductions in HbA1c and Body Weight With Once-Weekly Semaglutide Vs Comparators Across Baseline BMI Subgroups: Posthoc Analysis of SUSTAIN 1–5 and 7–10


1 month 3 weeks ago

In the SUSTAIN trial program, once-weekly (OW) semaglutide, a GLP-1RA approved for type 2 diabetes treatment, significantly reduced HbA1c and body weight (BW) vs all comparators, with a safety profile consistent with the GLP-1RA class.
Sara Stafford, Vanita R. Aroda, Ofir Frenkel, Juan Frias, Charlotte Hindsberger, Silas Gylvin, Carel Le Roux, Sten Madsbad

60 - Efficacy of Oral Semaglutide According to Race: An Exploratory Subgroup Analysis of the PIONEER Trial Program


1 month 3 weeks ago

The global PIONEER program investigated the efficacy and safety of oral semaglutide, a glucagon-like peptide-1 receptor agonist. Patients with type 2 diabetes were randomized to once-daily oral semaglutide (3, 7 or 14 mg, or flexibly dosed [flex]), placebo or active comparator (empagliflozin 25 mg, sitagliptin 100 mg or liraglutide 1.8 mg). This exploratory subgroup analysis evaluated the effect of race on glycated hemoglobin (HbA1c) and body weight (BW) reductions at the end of treatment (week 26, 52 or 78).
Cyrus Desouza, Aslam Amod, Klaus Kallenbach, Peter Lin, Morten A. Nielsen, Eduard Montanya

61 - Comparable Efficacy of Once-Weekly Subcutaneous Semaglutide in Subjects With Type 2 Diabetes Aged <65 and ≥65 Years: SUSTAIN 1–5 and 7–10 Posthoc Analysis


1 month 3 weeks ago

In the phase 3 SUSTAIN clinical trial program, once-weekly semaglutide was more effective than comparators at lowering HbA1c and body weight in subjects with type 2 diabetes (T2D). This posthoc analysis of SUSTAIN 1–5 and 7–10 compared efficacy of semaglutide in subjects <65 years (nonelderly) with those ≥65 years (elderly) vs placebo and active comparators. These comparisons were reported individually, by trial.
Akshay Jain, Mark L. Warren, Charlotte Hindsberger, Jack Lawson, Bernhard Ludvik, Sascha Pilemann-Lyberg, Adie Viljoen

63 - Glycemic and Body Weight Responses to Oral Semaglutide in the PIONEER Trial Program


1 month 3 weeks ago

The PIONEER phase 3 program investigated glycemic response and other efficacy endpoints in patients with type 2 diabetes randomized to oral semaglutide (3, 7 or 14 mg once daily), placebo or active comparator (empagliflozin 25 mg, sitagliptin 100 mg or liraglutide 1.8 mg once-daily). This posthoc analysis of PIONEER 1–5 and 8 trials evaluated the response of any reduction in HbA1c (%) and/or body weight (%), and a clinically relevant composite endpoint of HbA1c reduction ≥1% and body weight loss ≥5% with semaglutide 14 mg vs comparators at treatment end (26–78 weeks).
Kathleen Dungan, Christin Løth Hertz, Linda Mellbin, Morten A. Nielsen, Vincent Woo, Tina Vilsbøll

64 - Real-World Use of Once-Weekly Semaglutide in Patients With Type 2 Diabetes: Results From SURE Canada


1 month 3 weeks ago

In the SUSTAIN clinical trials, once-weekly (OW) subcutaneous semaglutide demonstrated superior glycated hemoglobin (HbA1c) and body weight (BW) reductions in adults with type 2 diabetes (T2D). SURE Canada (NCT03457012) is a multicentre, prospective, noninterventional study investigating the effectiveness of OW semaglutide in a real-world setting.
Jean-François Yale, Andrei-Mircea Catarig, Umut Erhan, Katrine Grau, Agnieszka Klimek-Abercrombie, Laura Reardon, Remi Rabasa-Lhoret, Vincent Woo, Joanne Liutkus

65 - Randomized Comparison of Initiating Insulin Glargine or Iglarlixi in South Asian Canadians With Type 2 Diabetes: VARIATION 2 SA Trial


1 month 3 weeks ago

To compare initiation of a fixed-ratio combination of glargine-lixisenatide (iGlarLixi) and insulin glargine U100 (iGlar), exclusively in South Asian origin Canadians.
Harpreet Bajaj, Lisa Chu, Nandini Bansal, Ruth Brown, Gagandeep Dhillon, Rishabh Gupta, Jatminderpal S. Bhela, Jagjit Padda, Hasnain Khandwala, Karri Venn, Ronnie Aronson

66 - Elimination of Hepatocyte Dpp4 Does Not Alter Markers of Liver Disease Progression in Aged, High-Fat, High-Cholesterol-Fed Mice


1 month 3 weeks ago

In tandem with dyslipidemia, approximately 70% of patients with type 2 diabetes will develop nonalcoholic fatty liver disease, a chronic disease that ranges from simple steatosis to severe cirrhosis characterized by inflammation and fibrosis. Previous studies have demonstrated that circulating DPP4 is shed from hepatocytes and has a direct proinflammatory role in liver and adipose tissue. Therefore, this study aimed to evaluate the efficacy of eliminating hepatic Dpp4 in the progression of liver disease.
Natasha Trzaskalski, Branka Vulesevic, Evgenia Fadzeyeva, My-Anh Nguyen, Erin E. Mulvihill

67 - Diabetes Prescribing Patterns of SGLT2i and GLP-1RA in Northern Alberta Primary Care: A Closer Look at Those With Cardiovascular Disease, Heart Failure and Chronic Kidney Disease


1 month 3 weeks ago

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown benefits in patients with diabetes and cardiovascular disease (CVD), and increasing evidence indicates benefits in those with chronic kidney disease (CKD) and heart failure. This study aims to describe current glucose-lowering medication prescribing patterns in Northern Alberta primary care settings.
Robin C. Hao, Tyler Myroniuk, Nandini Desai, Donna Manca, Denise Campbell-Scherer, Roseanne O. Yeung

68 - Flaxseed Lignan Complex Consumption Fails to Reduce Hypertension in Older Type 2 Diabetes Patients


1 month 3 weeks ago

Hypertension in type 2 diabetes patients (T2DP) contributes significantly to myocardial infarction and stroke. Unknown is the impact of flaxseed lignan complex (FLC) on Diabetes Canada’s clinical practice guidelines-defined (DCCPG-D) systolic hypertension (SH) and/or diastolic hypertension (DH) in older T2DP. It was hypothesized that FLC (600 mg secoisolariciresinol diglucoside (SDG)/day) for 3 months would decrease DCCPG-D SH and/or DH in older T2DP. The objective was to test this hypothesis.
Douglas E. Barre

69 - Age- and Sex-Specific Incidence of Severe Hypoglycemia in Type 2 Diabetes (InHypo-DM Study)


1 month 3 weeks ago

Increased evidence on the real-world age- and sex-specific incidence of severe hypoglycemia (SH) in type 2 diabetes (T2DM) could reveal straightforward yet impactful targets for improved clinical and public health interventions.
Alexandria Ratzki-Leewing, Kathryn Stirling, Susan Webster-Bogaert, Judith B. Brown, Sonja M. Reichert, Bridget l. Ryan, Stewart Harris

70 - The Next Generation Birth Cohort: Screening for Dysglycemia and Albuminuria in High-Risk Children


1 month 3 weeks ago

Youth-onset type 2 diabetes (T2D) is increasing worldwide. The prevalence of dysglycemia and microalbuminuria prior to diagnosis remains unclear. This project examined the presence of dysglycemia and albuminuria prior to diagnosis in youth with T2D, and compared rates of albuminuria in youth-onset T2D compared to normoglycemic youth.
Yash Rawal, Elizabeth Sellers, Allison Dart, Christy Pylypjuk, Brandy A. Wicklow

71 - Insulin (Ins2) Is Expressed in the Brain and Its Global Deletion Leads to Learning Deficits, Anxiety and Reduced Hippocampal Cyclin D1 Expression in Female Mice


1 month 3 weeks ago

Insulin dysregulation independently underlies diabetes and Alzheimer’s Disease (AD). The former has also been shown to be a risk factor for the latter. The ancestral insulin gene (Ins2), but not the Ins1 gene, is transcribed locally within the brain in mice. We confirmed that neuronal expression of Ins2 is abundant within the hippocampus, a region with established roles in learning and memory. Public single cell RNA sequencing datasets were analyzed to determine the specific cell types where Ins2 is expressed in the mouse brain.
Stella Baehring, Timothy O’leary, Neeki Alavi, Danae Holenka, Hong Li, Arya Mehran, Manuel Belmadani, Paul Pavalidis, Shernaz Bamji, James Johnson

72 - Single Cell RNA Sequencing Points to Altered IL-10 Signalling and Metabolism in Hyperinsulinemia-Driven Pancreatic Cancer Initiation


1 month 3 weeks ago

Epidemiological studies have shown hyperinsulinemia is independently associated with increased pancreatic ductal adenocarcinoma (PDAC) morbidity and mortality. We recently showed direct in vivo evidence that hyperinsulinemia promotes PDAC. Using a mouse model of PDAC development (Ptf1aCreER;LSL-KrasG12D) crossed with Ins1+/-;Ins2-/- alleles that result in ∼50% reduced fasting insulin, we found a ∼50% reduction in pancreatic intraepithelial neoplasia (PanIN) precancerous lesions compared with Ins1+/+;Ins2-/- control mice.
Anni Zhang, Twan De Winter, Xioake Hu, Hong Li, Janel Kopp, James Johnson

73 - Characterization and Flaws of a New Potential β-Cell-Specific Mouse Line


1 month 3 weeks ago

Development and thorough characterization of genetic tools is necessary for efficient and productive understanding of the beta cell. Over the past few years, multiple mouse lines expressing Cre recombinase in beta cells have been developed, but all have significant caveats towards their use. Our laboratory has invested significant effort into characterizing new and existing lines to provide a model for the beta cell community. Our goal is to provide a mouse that 1) has efficient, inducible Cre expression; 2) only in beta cells and 3) limits the need for drug administration (i.e.
Nathalie Jouvet, Emilie Courty, Khalil Bouyakdan, Thierry Alquier, Jennifer L. Estall

74 - Reactive Oxygen Species Are Implicated in Nutrient-Induced β-Cell Proliferation


1 month 3 weeks ago

In individuals living with obesity without diabetes, β-cell mass accretion maintains glucose homeostasis by balancing levels of circulating insulin and insulin resistance. Type 2 diabetes appears when these compensatory mechanisms fail. Deciphering the pathways controlling β-cell proliferation has, thus, become a major research goal in the hope to identify therapeutic targets to expand β-cell mass and prevent or delay the onset of diabetes. Previously, we demonstrated that the fatty acid mixture ClinOleic (65% oleate) potentiates glucose-induced β-cell proliferation in vivo in rats.
Alexis Vivoli, Julien Ghislain, Anne-Laure Castell, Alain Pacis, Robert Sladek, Vincent Poitout

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