Abstract
Background: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that plays an important role in glucose homeostasis and food intake. In people, GLP-1 receptor agonists (GLP-1RAs) are commonly used for the treatment of type 2 diabetes mellitus (DM) and obesity; however, non-adherence to injectable medications is common. OKV-119 is an investigational drug delivery system intended for subdermal implantation and delivery of the GLP-1RA exenatide for up to 6 months.Hypothesis/Objectives: Develop protocols for the subcutaneous (SC) insertion and removal of OKV-119 and to evaluate its tolerability, in vivo drug-releasing characteristics, and weight-loss effects in cats.Animals: Two cadaveric and 19 purpose-bred cats.Methods: In cadavers, OKV-119 insertion protocol and imaging were performed at three SC locations. The safety and tolerability of OKV-119 implants were assessed in a small (n = 4 cats) 62-day study. Weekly plasma exenatide concentrations and body weight were measured in a 42-day proof-of-concept study designed to evaluate OKV-119 prototypes implanted in cats (n = 15).Results: In anesthetized cats, the duration of insertion and removal procedures was 1–2 min. OKV-119 was easily identified on radiographs, and well-tolerated without any apparent implant site reactions. Following implantation, exanatide plasma concentrations were observed for up to 35 days. Plasma exenatide concentrations were correlated to weight loss.Conclusion and clinical importance: Our findings suggest that OKV-119 could be easily inserted and removed during a routine clinic visit and can be used to safely and effectively deliver exenatide. Future studies of OKV-119, configured to release exenatide for a longer extended months-long duration, are warranted to determine whether the combination of metabolic improvements and beneficial weight-loss, coupled with minimal impact on pet-owner's lifestyle, lead to improved outcomes for obese cats and feline DM patients.
Highlights
Glucagon-like peptide-1 (GLP-1), an important incretin hormone that is secreted from the intestines during a meal and participates in the regulation of systemic metabolism, food intake, gastrointestinal motility, and more [1]
Data in cats demonstrate that GLP-1 receptor agonists (GLP-1RA) generally have similar effects to those seen in human patients and might be useful in treating feline diabetes mellitus (DM) [9,10,11,12,13,14,15,16]
Obesity in cats is associated with numerous cormobidities including DM, osteoarthritis, impaired respiratory function, and certain types of neoplasia [18, 19]
Summary
Glucagon-like peptide-1 (GLP-1), an important incretin hormone that is secreted from the intestines during a meal and participates in the regulation of systemic metabolism, food intake, gastrointestinal motility, and more [1]. GLP-1 receptor agonists (GLP-1RAs) are a cornerstone treatment of type 2 diabetes mellitus (DM) in human medicine [2], with exenatide being the first-in-class GLP-1RA to be approved [3]. GLP-1RAs have been shown to beneficially reduce body weight in non-diabetic obese people, without causing hypoglycemia or other serious adverse events (AEs) [4,5,6,7]. Given the clinical challenge of managing feline obesity [19, 20], it is intriguing to determine whether, like in human medicine, GLP-1RAs administered to non-diabetic, clinically obese cats can be used to treat obesity and prevent, or delay, the onset of DM and other untoward health outcomes. GLP-1 receptor agonists (GLP-1RAs) are commonly used for the treatment of type 2 diabetes mellitus (DM) and obesity; non-adherence to injectable medications is common. Hypothesis/Objectives: Develop protocols for the subcutaneous (SC) insertion and removal of OKV-119 and to evaluate its tolerability, in vivo drug-releasing characteristics, and weight-loss effects in cats.
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