Glucose Metabolism and Metabolic Syndrome in Horses and Donkeys: Emerging Comparative Insights

Donkeys and horses diverged approximately 4 million years ago and exhibit substantial genetic, chromosomal, and physiologic differences. Although mostly studied in horses, metabolic syndrome represents a broader metabolic dysfunction with systemic consequences, such as obesity and laminitis, that can impact the quality of life of equids. This review summarizes the current knowledge of glucose and insulin regulation in healthy horses and donkeys and examines the pathophysiology of equine metabolic syndrome (EMS) in comparison with donkey metabolic syndrome (DMS), including insulin dysregulation, impaired glucose transport, adipose tissue dysfunction, and emerging evidence of systemic meta-inflammation and oxidative stress. Compared with horses, donkeys demonstrate distinct patterns of adipose deposition, different metabolic profiles, and altered glucose and insulin dynamics following oral soluble carbohydrate intake. While our understanding of donkey medicine has expanded in recent years, gaps in knowledge remain regarding mechanistic insights into glucose metabolism and dysregulation in donkeys. Finally, we evaluate current and emerging therapeutic strategies, including dietary management, exercise, nutraceuticals, and pharmacologic interventions such as metformin and sodium–glucose cotransporter 2 inhibitors (SGLT2is). While these therapeutic approaches have demonstrated efficacy in horses, evidence in donkeys remains extremely limited. This highlights a critical need for species-specific research to elucidate the pathophysiological mechanisms and optimize therapeutic strategies for donkeys.