A review of recent developments in the pharmacological prevention and treatment of endocrinopathic laminitis

Abstract

Despite the prevalence of endocrinopathic laminitis, the pharmacologic options for preventing and treating the disease are severely limited. The present review aims to discuss the spectrum of potential therapeutic agents for the condition, ranging from early experimental compounds to agents nearing registration. There are different pharmacologic targets for, and approaches to, managing laminitis. Reducing hyperinsulinaemia is central to diminishing endocrinopathic laminitis risk, and a detailed understanding of the pathophysiology of insulin dysregulation is necessary to identify pathways that can be targeted to minimise post-prandial insulin secretion and action. This area of research is advancing rapidly, with several exciting prospects, such as sodium-dependent glucose co-transporter-2 inhibitors, on the horizon for the treatment of equine metabolic dysfunction. Drugs that directly target the lamellae and aim to reduce the damage inflicted on the lamellae as part of this condition, are not yet available. Although progress in this area of laminitis therapy is slower, improved understanding of the events that lead to lamellar failure has enabled the investigation of novel drugs that aim to prevent laminitis at the site of the lesion. Finally, a brief review is included of the directions being taken in the management of the chronic and acute pain that accompanies laminitis. Medications for relieving the pain associated with laminitis are currently the most-prescribed drugs for the disease, and range from simple, affordable and thoroughly tested options, such as phenylbutazone, to newer, less-understood applications such as paracetamol and gabapentin. In the future, endocrinopathic laminitis management plans will likely take a multi-faceted approach that still hinge on effective dietary management and exercise, but also include drugs that address foot pathology, pain and underlying endocrine disturbances.

Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: A case series

“…The improvement in laminitis in association with a reduction in insulin concentration following ertugliflozin treatment is consistent with recent research that has demonstrated a link between hyperinsulinaemia and laminitis (de Laat & Sillence, 2020). Insulin concentrations have been shown to be associated with future risk of laminitis (Knowles et al, 2021; Menzies‐Gow et al, 2017), and reduction in insulin concentration is therefore assumed to reduce the risk of clinical laminitis developing (de Laat & Sillence, 2020).…”

“…The improvement in laminitis in association with a reduction in insulin concentration following ertugliflozin treatment is consistent with recent research that has demonstrated a link between hyperinsulinaemia and laminitis (de Laat & Sillence, 2020). Insulin concentrations have been shown to be associated with future risk of laminitis (Knowles et al, 2021; Menzies‐Gow et al, 2017), and reduction in insulin concentration is therefore assumed to reduce the risk of clinical laminitis developing (de Laat & Sillence, 2020). The speed and magnitude of improvement in lameness was unexpected, given that these were chronic cases; to the authors' knowledge, this is the first study to report a rapid improvement in clinical laminitis following the use of drugs that reduce insulin concentrations.…”

“…Hyperinsulinaemia has been identified to be central to the development of laminitis in horses and ponies (hereafter referred to collectively as horses) with equine metabolic syndrome (EMS) (de Laat & Sillence, 2020; Frank & Tadros, 2014). Laminitis can be induced experimentally following exogenous administration of insulin (Asplin et al, 2007; de Laat et al, 2010), and high serum insulin concentrations are a reliable predictor of future episodes of laminitis (Knowles et al, 2021; Meier et al, 2018a, 2018b; Menzies‐Gow et al, 2017).…”

“…Whilst the exact mechanism by which hyperinsulinaemia causes laminitis is unclear, and other theories are postulated, it has been suggested that insulin may stimulate insulin‐like growth factor‐1 receptors within the lamellae resulting in cellular proliferation, weakening and subsequent lamellar failure (de Laat et al, 2011, 2013). Reducing serum insulin concentration is therefore considered to be an effective means of preventing hyperinsulinaemia‐associated laminitis (HAL) and is advocated in the management of horses with laminitis and equine metabolic syndrome (de Laat & Sillence, 2020).…”

“…Levothyroxine administration is associated with a reduction in insulin concentrations and a doubling of insulin sensitivity (Frank et al, 2008; Sommardahl et al, 2005). Compounds such as glucagon like peptide‐1 inhibitors, pioglitazone and sweet taste inhibitors have also been identified as having potential for reducing hyperinsulinaemia but are not used in clinical practice currently (de Laat & Sillence, 2020; Durham et al, 2019).…”