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Drug release profile of a novel exenatide long-term drug delivery system (OKV-119) administered to cats

Klotsman M, Anderson WH, Gilor C. Drug release profile of a novel exenatide long-term drug delivery system (OKV-119) administered to cats. BMC Vet Res. 2024 May 18;20(1):211. PMID: 38762728; PMCID: PMC11102179. doi: 10.1186/s12917-024-04051-6.


GLP-1 agonists have been used for several years as a treatment for diabetes mellitus in human medicine. Long acting GLP-1 agonists have been demonstrated to be effective tools in lowering insulin requirements and glycemic variation in cats with diabetes, however have not been widely adopted by practitioners for this purpose.

GLP-1 agonists, like exenatide used in this study, work by mimicking the effects of a naturally occurring hormone called glucagon-like peptide-1 . GLP-1 is produced in the gut and plays a key role in blood sugar regulation and appetite control. By mimicking GLP-1’s actions, GLP-1 agonists lead to increased insulin secretion, decreased glucagon secretion, slower gastric emptying, and increased satiety signals. These combined effects contribute to improved blood sugar control and weight management, making them valuable tools for treating type 2 diabetes and obesity.

In recent years, the GLP-1 agonist semaglutide (Ozempic) has been approved and used in humans as a weight loss tool. Given the current feline obesity epidemic, there is interest in the use of similar drugs to reduce obesity in cats. The study explores the potential of GLP-1 receptor agonists as a therapeutic strategy for feline obesity. Studies conducted in healthy, purpose-bred cats have shown that short-term administration of GLP-1 agonists are correlated with weight loss, however, the weight-loss properties of GLP-1 agonists administered to cats over a longer duration are not described.

The primary purpose of this study was to characterize exenatide plasma concentrations over a 112 day study period in healthy cats implanted with a single OKV-119 implant. Secondary objectives were to evaluate caloric intake and body weight following exposure to exenatide. The researchers implanted a sustained-release exenatide delivery device in five purpose-bred cats. The implant was designed to deliver exenatide for a period of 84 days . Food intake, body weight, and plasma exenatide concentrations were monitored throughout the study.

Four out of the five cats exhibited a reduction in caloric intake and body weight following implantation. Plasma exenatide concentrations remained above baseline levels for over 84 days in all cats. From Day 0 to Day 28, a decreased caloric intake was observed following insertion of the OKV-119 implant in Cats 1–4. During this period, food intake was correlated to weekly declines in body weights Body weights for these cats declined for the first 28 days, after which they remained stable to Day 112.

From Days 1 to 7,  Cat 1 experienced near complete anorexia and was offered canned wet food between Day 8 and Day 20 to facilitate eating. This was a significant adverse effect, and if it is replicable in 20% of cats as this (albeit very small) study would suggest, could dramatically limit the use of this drug.

This paper has several limitations, including the small sample size and the use of purpose-bred cats, which may not be generalizable to the broader feline population. Cats were not obese, and as such do not accurately replicate the physiology of the typical candidate for this medication. Further investigations are warranted to evaluate the efficacy and safety of this drug delivery system in a larger, more diverse group of cats. ~MK


See Also
Wall M, Cave NJ, Vallee E. Owner and Cat-Related Risk Factors for Feline Overweight or Obesity. Front Vet Sci. 2019 Aug 19;6:266. doi: 10.3389/fvets.2019.00266. PMID: 31482097; PMCID: PMC6709657.

Clark M, Hoenig M. Feline comorbidities: Pathophysiology and management of the obese diabetic cat. J Feline Med Surg. 2021 Jul;23(7):639-648. doi: 10.1177/1098612X211021540. PMID: 34167340; PMCID: PMC10812123.

Gilor C, Rudinsky AJ, Hall MJ. New Approaches to Feline Diabetes Mellitus: Glucagon-like peptide-1 analogs. J Feline Med Surg. 2016 Sep;18(9):733-43. doi: 10.1177/1098612X16660441. PMID: 27562982.