Browsing by Subject "Sacubitril"

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    Insulinotropic Effects of Neprilysin and/or Angiotensin Receptor Inhibition in Mice
    (Frontiers Media, 2022-06-06) Esser, Nathalie; Schmidt, Christine; Barrow, Breanne M.; Cronic, Laura; Hackney, Daryl J.; Mongovin, Stephen M.; Hogan, Meghan F.; Templin, Andrew T.; Castillo, Joseph J.; Hull, Rebecca L.; Zraika, Sakeneh; Medicine, School of Medicine
    Treatment of heart failure with the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan improved glycemic control in individuals with type 2 diabetes. The relative contribution of neprilysin inhibition versus angiotensin II receptor antagonism to this glycemic benefit remains unknown. Thus, we sought to determine the relative effects of the neprilysin inhibitor sacubitril versus the angiotensin II receptor blocker valsartan on beta-cell function and glucose homeostasis in a mouse model of reduced first-phase insulin secretion, and whether any beneficial effects are additive/synergistic when combined in sacubitril/valsartan. High fat-fed C57BL/6J mice treated with low-dose streptozotocin (or vehicle) were followed for eight weeks on high fat diet alone or supplemented with sacubitril, valsartan or sacubitril/valsartan. Body weight and fed glucose levels were assessed weekly. At the end of the treatment period, insulin release in response to intravenous glucose, insulin sensitivity, and beta-cell mass were determined. Sacubitril and valsartan, but not sacubitril/valsartan, lowered fasting and fed glucose levels and increased insulin release in diabetic mice. None of the drugs altered insulin sensitivity or beta-cell mass, but all reduced body weight gain. Effects of the drugs on insulin release were reproduced in angiotensin II-treated islets from lean C57BL/6J mice, suggesting the insulin response to each of the drugs is due to a direct effect on islets and mechanisms therein. In summary, sacubitril and valsartan each exert beneficial insulinotropic, glycemic and weight-reducing effects in obese and/or diabetic mice when administered alone; however, when combined, mechanisms within the islet contribute to their inability to enhance insulin release.
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    Relation of household income to access and adherence to combination sacubitril/valsartan in heart failure: a retrospective analysis of commercially insured patients
    (American Heart Association, 2022) Johnson, Amber E.; Swabe, Gretchen M.; Addison, Daniel; Essien, Utibe R.; Breathett, Khadijah; Brewer, LaPrincess C.; Mazimba, Sula; Mohammed, Selma F.; Magnani, Jared W.; Medicine, School of Medicine
    Background: Outcomes in heart failure with reduced ejection fraction (HFrEF) are influenced by access and adherence to guideline-directed medical therapy. Our objective was to study the association between annual household income and: (1) the odds of having a claim for sacubitril/valsartan among insured patients with HFrEF and (2) medication adherence (measured as the proportion of days covered). We hypothesized that lower annual household income is associated with decreased odds of having a claim for and adhering to sacubitril/valsartan. Methods: Using the Optum de-identified Clinformatics Data Mart, patients with HFrEF and ≥6 months of enrollment for follow-up (2016-2020) were included. Covariates included age, sex, race, ethnicity, educational attainment, US region, number of prescribed medications, and Elixhauser Comorbidity Index. Prescription for sacubitril/valsartan was defined by the presence of a claim within 6 months of HFrEF diagnosis. Adherence was defined as proportion of days covered ≥80%. We fit multivariable-adjusted logistic regression models and hierarchical logistic regression accounting for covariates. Results: Among 322 007 individuals with incident HFrEF, 135 282 had complete data for analysis. Of the patients eligible for sacubitril/valsartan, 4.7% (6372) had a claim within 6 months of HFrEF diagnosis. Following multivariable adjustment, individuals in the lowest annual income category (<$40 000) were significantly less likely (odds ratio, 0.83 [95% CI, 0.76-0.90]) to have a sacubitril/valsartan claim within 6 months of HFrEF diagnosis than those in the highest annual income category (≥$100 000). Annual income <$40 000 was associated with lower odds of proportion of days covered ≥80% compared with income ≥$100 000 (odds ratio, 0.70 [95% CI, 0.59-0.83]). Conclusions: Lower household income is associated with decreased likelihood of a sacubitril/valsartan claim and medication adherence within 6 months of HFrEF diagnosis, even after adjusting for sociodemographic and clinical factors. Future analyses are needed to identify additional social factors associated with delays in sacubitril/valsartan initiation and long-term adherence.