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Journal of veterinary pharmacology and therapeutics2024; 48 Suppl 1(Suppl 1); 31-40; doi: 10.1111/jvp.13470

Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses.

Abstract: Laminitis is a common and painful condition of the equine foot and approximately 90% of cases are associated with insulin dysregulation (ID) that is a central feature of the common endocrine disorder equine metabolic syndrome (EMS) and occurs in a subset of animals with pituitary pars intermedia dysfunction. Additional features of EMS include obesity, altered circulating concentrations of adipokines (particularly adiponectin and leptin) and hypertriglyceridaemia. Obesity, ID, hypoadiponectinaemia, hyperleptinaemia and an altered plasma lipid profile are also features of human metabolic syndrome (HMS) alongside hyperglycaemia. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of oral hypoglycaemic agents used in combination with lifestyle changes in the management of HMS. SGLT2 receptors are responsible for 90% of the renal glucose reabsorption that occurs in the proximal convoluted tubule. Thus, these drugs increase urinary glucose excretion by suppressing glucose reabsorption from the glomerular filtrate resulting in urinary calorie loss with consequent weight loss and improvements in ID, hyperglycemia, hypoadiponectinaemia and hyperleptinaemia. There are no licenced veterinary drugs available for treating ID and preventing insulin-associated laminitis in horses. Thus, the use of SGLT2i for the control of equine hyperinsulinaemia with the goal of improving recovery from associated active laminitis or preventing future laminitis has recently been advocated. There are a small number of published studies reporting the use of the SGLT2i canagliflozin, ertugliflozin and velagliflozin to aid the management of equine ID. However, the doses used are largely extrapolated from human studies with limited consideration of species-specific variations. In addition, there is limited evaluation of the fundamental differences between ID in horses and humans, particularly the fact that most horses with ID remain hyperinsulinaemic but normoglycaemic such that increased urinary loss of glucose may not explain the beneficial effects of these drugs. Further study of the potential deleterious effects of treatment-associated hypertriglyceridaemia is required together with the effect of SGLT2i therapy on circulating concentrations of adipokines in horses.
© 2024 The Author(s). Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.
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Publication Date: 2024-07-10 PubMed ID: 38984777PubMed Central: PMC11736997DOI: 10.1111/jvp.13470Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper explores the use of Sodium-glucose transport protein 2 inhibitors (SGLT2i) in treating insulin dysregulation in horses and ponies, particularly related to laminitis – a common and painful hoof condition.

Background and problem statement

  • The research primarily focuses on laminitis, a prevalent foot ailment in horses linked to nearly 90% of insulin dysregulation cases, which is a core feature of the prevalent endocrine disorder known as the equine metabolic syndrome (EMS).
  • Alongside laminitis, EMS is characterised by obesity; altered circulating concentrations of adipokines ‘adiponectin and leptin’; and hypertriglyceridaemia, a condition where there’s an excess of triglycerides in the blood. Similar symptoms, apart from hyperglycaemia, are observed in the human metabolic syndrome (HMS).
  • Currently, there are no officially licenced veterinary drugs to prevent insulin-associated laminitis in horses.

Potential Solution with SGLT2i

  • The paper discusses the use of Sodium-glucose transport protein 2 inhibitors (SGLT2i) in managing insulin dysregulation. SGLT2i are a newfound class of oral hypoglycaemic agents used, in tandem with lifestyle changes, to treat HMS in humans.
  • SGLT2 receptors are vital for glucose reabsorption – accounting for about 90% of the renal glucose reabsorption in the proximal convoluted tubule. SGLT2i drugs heighten urinary glucose excretion by suppressing glucose reabsorption, resulting in urinary calorie loss that leads to weight loss and improvement in insulin dysregulation and other conditions including hyperglycemia, hypoadiponectinaemia, and hyperleptinaemia.
  • Notably, the use of SGLT2i has recently been promoted to control equine hyperinsulinaemia – aiming at enhancing recovery from active laminitis or preventing future occurrences.

Existing Studies and Key Issues

  • A few studies have reported the use of SGLT2i drugs like canagliflozin, ertugliflozin and velagliflozin to help manage equine insulin dysregulation. However, these studies primarily extrapolate doses from human studies, overlooking the relevance of species-specific differences.
  • Crucially, these studies do not thoroughly examine the fundamental differences between insulin dysregulation in horses and humans. For instance, the majority of horses with insulin dysregulation remain hyperinsulinaemic but normoglycaemic – thus, an increased urinary loss of glucose may not necessarily explain the positive impacts of these drugs.
  • The research paper calls for further investigation of potential harmful effects of treatment-related hypertriglyceridaemia, along with a detailed study on the impacts of SGLT2i treatment on circulating concentrations of adipokines in horses.

Cite This Article

APA
Menzies-Gow NJ, Knowles EJ. (2024). Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses. J Vet Pharmacol Ther, 48 Suppl 1(Suppl 1), 31-40. https://doi.org/10.1111/jvp.13470

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 48 Suppl 1
Issue: Suppl 1
Pages: 31-40

Researcher Affiliations

Menzies-Gow, Nicola J
  • Department of Clinical Science and Services, Royal Veterinary College, Hertfordshire, UK.
Knowles, Edward J
  • Department of Clinical Science and Services, Royal Veterinary College, Hertfordshire, UK.

MeSH Terms

  • Animals
  • Horses
  • Horse Diseases / drug therapy
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • Insulin / metabolism
  • Foot Diseases / veterinary
  • Foot Diseases / drug therapy
  • Hyperinsulinism / veterinary
  • Hyperinsulinism / drug therapy
  • Metabolic Syndrome / veterinary
  • Metabolic Syndrome / drug therapy

Conflict of Interest Statement

Nicola Menzies‐Gow has previously served as a consultant for and received payments for educational material from Boehringer Ingelheim. Edward J. Knowles is employed by CVS UK Ltd and provides clinical diagnostic services through Axiom Veterinary Laboratory. He has received payments from Boehringer Ingelheim for educational material.

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