Evaluation of the tolerance and effects of 1-deoxynojirimycin on insulin and glucose dynamics in healthy horses and horses at risk for insulin dysregulation

Abstract Background Insulin dysregulation (ID) is common and diminishes welfare of horses. Current management relies on diet and exercise, with variable responses and limited medical options. Alpha-glucosidase inhibitors (AGIs) might provide adjunctive therapy. Hypothesis/Objectives To evaluate the tolerance and effects of Reducose®, a Morus alba leaf extract standardized to 5% 1-deoxynojirimycin (DNJ), in healthy horses and horses at risk of ID. We hypothesized DNJ would be well-tolerated and reduce insulin responses to oral sugar tests (OSTs). Animals Twenty-seven horses: 6 healthy (Phase I), 5 at risk for ID (Phase II), and 16 at risk for ID (Phase III). Methods Prospective, 3-phase study. Phase I assessed tolerance of escalating oral DNJ doses (0-5000 mg q12h, 7 days each). Phase II evaluated dose-dependent effects on OST response (0-5000 mg q12h, 7 days each). Phase III assessed duration of effect (0-3 h pre-OST) at 2500 and 5000 mg q12h (28 days each). Primary outcomes were peak insulin and insulin area under the curve (AUC). Results DNJ caused no adverse effects. Insulin responses decreased in a dose- and time-dependent manner. At 5000 mg q12h, peak insulin fell from 33.4 ± 15.1 μIU/mL to 18.8 ± 9.2 μIU/mL; AUC decreased by −18.6 μIU·h/mL (95% CI, −31.7 to −5.5). In Phase III, 5000 mg significantly reduced peak insulin when OST was performed 0 h (−13.1 μIU/mL, 95% CI, −18.1 to −8.2) and 1 h (−7.4 μIU/mL, 95% CI, −12.5 to −2.4) after DNJ. Insulin AUC mirrored peak insulin. Conclusions and clinical importance DNJ was well-tolerated and attenuated insulin responses to OST, supporting its potential as adjunctive therapy for ID in horses.