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

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.