Menzies-Gow Nicola J, Knowles Edward J
Department of Clinical Science and Services, Royal Veterinary College, Hertfordshire, UK.
J Vet Pharmacol Ther. 2025 Jan;48 Suppl 1(Suppl 1):31-40. doi: 10.1111/jvp.13470. Epub 2024 Jul 10.
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.
蹄叶炎是马足部常见且疼痛的病症,约90%的病例与胰岛素调节异常(ID)有关,ID是常见内分泌疾病马属动物代谢综合征(EMS)的核心特征,且发生于部分患有垂体中间叶功能障碍的动物。EMS的其他特征包括肥胖、脂肪因子(特别是脂联素和瘦素)循环浓度改变以及高甘油三酯血症。肥胖、ID、低脂联素血症、高瘦素血症和血浆脂质谱改变也是人类代谢综合征(HMS)的特征,同时伴有高血糖。钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)是一类新型口服降糖药,用于联合生活方式改变来管理HMS。SGLT2受体负责近端曲管中90%的肾葡萄糖重吸收。因此,这些药物通过抑制肾小球滤液中的葡萄糖重吸收来增加尿糖排泄,导致尿热量损失,从而减轻体重,并改善ID、高血糖、低脂联素血症和高瘦素血症情况。目前没有用于治疗马ID和预防胰岛素相关性蹄叶炎的获批兽药。因此,最近有人主张使用SGLT2i来控制马的高胰岛素血症,以改善相关活动性蹄叶炎的恢复情况或预防未来的蹄叶炎。有少数已发表的研究报告了使用SGLT2i卡格列净、依鲁格列净和维格列净来辅助管理马的ID。然而,所使用的剂量大多是从人体研究中推断出来的,对物种特异性差异考虑有限。此外,对于马和人ID之间的根本差异评估有限,特别是大多数患有ID的马仍处于高胰岛素血症但血糖正常的情况,因此尿糖损失增加可能无法解释这些药物的有益作用。需要进一步研究治疗相关高甘油三酯血症的潜在有害影响以及SGLT2i疗法对马体内脂肪因子循环浓度的影响。