Mouse Anti-Human GLP-1(aa 7-36) monoclonal antibody, clone N92485 [Biotin]

Aim To compare 6-month adherence, persistence and treatment patterns among patients initiating once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs), dulaglutide versus semaglutide, and dulaglutide versus exenatide BCise, using claims from the HealthCore Integrated Research Database. Materials and methods Patients aged >= 18 years, with type 2 diabetes, >= 1 claim for dulaglutide, semaglutide or exenatide BCise during the index period February 2018 to December 2018 (index date = earliest GLP-1RA fill date), no claim for GLP-1RAs in the 6-month pre-index period, and continuous enrolment 6 months pre- and post-index were included. Dulaglutide users were propensity-matched 1:1 to semaglutide users (3852 pairs) or exenatide BCise users (1879 pairs). The proportions of adherent (proportion of days covered >= 80%) patients were compared using chi-squared tests. Persistence, measured as days to discontinuation, was analysed using a Cox regression model. Results Matched cohorts (dulaglutide:semaglutide and dulagutide:exenatide BCise) were balanced in baseline characteristics and the mean age was 54 and 55 years, respectively, with approximately 51% and 49% women, respectively. At 6 months, significantly more dulaglutide users were adherent than semaglutide (59.7% vs. 42.7%;P <0.0001) or exenatide BCise users (58.1% vs. 40.3%;P <0.0001). Cox regression showed that dulaglutide users were less likely to discontinue therapy than semaglutide (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.66, 0.76) or exenatide BCise users (HR 0.59, 95% CI 0.53, 0.65;P <0.0001, both). Conclusion At 6-month follow-up, a higher proportion of patients initiating dulaglutide were adherent to and persistent with their treatment, compared to matched patients initiating either semaglutide or exenatide BCise.

Hepatocyte nuclear factor 1 alpha (HNF1 alpha) is a transcription factor required for normal insulin secretion and maintenance of beta-cell number in the pancreas. HNF1 alpha is also expressed in pancreatic alpha-cells, but its role in these cells is unknown. The aim of this study was to clarify the role of HNF1 alpha in alpha-cells. Male Hnf1a+/- mice with a mixed background were backcrossed to outbred ICR mice. Glucose tolerance, glucagon and insulin secretion, islet histology, and gene expression were investigated in ICR Hnf1a-/- and Hnf1a+/+ mice. Regulation of Slc5a1 (encoding sodium glucose cotransporter 1 [SGLT1]) expression by HNF1 alpha and the effect of SGLT1 inhibition on glucagon secretion were also explored. ICR Hnf1a-/- mice were glucose intolerant and exhibited impaired glucose-stimulated insulin secretion. The beta-cell area of ICR mice was decreased in Hnf1a-/- mice, but the alpha-cell area in the pancreas was similar between Hnf1a-/- and Hnf1a+/+ mice. Hnf1a-/- mice showed higher fasting glucagon levels and exhibited inadequate suppression of glucagon after glucose load. In addition, glucagon release in response to hypoglycemia was impaired in Hnf1a-/- mice, and glucagon secretion after 1.1 mM glucose administration, was also decreased in Hnf1a-/- islets. Slc5a1 expression was decreased in Hnf1a-/- islets, while HNF1 alpha activated the Slc5a1 promoter in alpha TC1-6 cells. Inhibition of SGLT1 suppressed 1.1 mM glucose-stimulated glucagon secretion in islets and alpha TC1-6 cells, but SGLT1 inhibition had no additional inhibitory effect in HNF1 alpha-deficient cells. Our findings indicate that HNF1 alpha modulates glucagon secretion in alpha-cells through the regulation of Slc5a1.