Effects of the Sodium-Glucose Cotransporter-2 Inhibitor Velagliflozin on Insulin Concentrations in Horses With Insulin Dysregulation.
Abstract: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are promising treatments to manage hyperinsulinemia in horses with insulin dysregulation (ID). Objective: The SGLT2i velagliflozin decreases insulin concentration in horses with ID. Methods: Privately-owned adult horses (n = 37) with laboratory-confirmed ID (low-dose oral sugar test insulin concentration > 75 μIU/mL). Methods: Double-blind randomized placebo-controlled trial. Horses received placebo (n = 19) or velagliflozin 0.3 mg/kg PO q24h (n = 18) for 20 weeks (Study Period 1, SP1) immediately followed by a 20-week open-label trial where all animals received velagliflozin (SP2). Analysis of resting insulin, glucose, and triglyceride concentrations and body condition score (BCS) was performed between treatment groups and study periods using a Mann-Whitney U test. For SP1, analysis of changes in biochemical analytes over time was performed using generalized linear mixed effects models (GLMM). Data are reported as median (interquartile range). Results: In SP1, GLMM indicated a significant effect of treatment on insulin concentration (71 [33-131] μIU/mL in horses receiving velagliflozin and 157 [82-298] μIU/mL in horses receiving placebo; p < 0.0001). The average (95% confidence interval [CI]) effect of velagliflozin treatment on insulin concentration was 155 (90-219) μIU/mL. Horses receiving placebo in SP1 had lower insulin (50 [26-99] μIU/mL) during SP2 (p < 0.0001). All horses experienced a transient increase in serum triglyceride concentration during velagliflozin treatment with no clinical abnormalities reported. In SP1, larger decreases in BCS occurred in horses receiving velagliflozin (median BCS 1 point lower than baseline; p = 0.02) than those receiving placebo. Conclusions: Velagliflozin significantly decreased resting insulin concentrations in horses with ID.
© 2025 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Publication Date: 2025-10-09 PubMed ID: 41063501PubMed Central: PMC12508266DOI: 10.1111/jvim.70256Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Veterinary
Summary
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Overview
- This study investigated the effects of the drug velagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), on insulin levels in horses diagnosed with insulin dysregulation (ID).
- The findings demonstrate that velagliflozin significantly reduces resting insulin concentrations in horses with ID compared to placebo treatment.
Background
- Insulin dysregulation (ID) in horses is a condition characterized by abnormal insulin metabolism and hyperinsulinemia, which can lead to metabolic diseases such as equine metabolic syndrome.
- Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a class of drugs primarily used in humans to reduce blood glucose by inhibiting reabsorption of glucose in the kidney, thereby lowering circulating glucose and insulin levels.
- Velagliflozin is an SGLT2 inhibitor being explored as a treatment option to manage hyperinsulinemia in horses with ID.
Study Objectives
- To evaluate the effects of velagliflozin on resting insulin concentrations in horses diagnosed with ID.
- To monitor any changes in glucose, triglycerides, and body condition scores (BCS) during treatment.
Methods
- Subjects: 37 privately-owned adult horses with confirmed ID, defined by resting insulin concentration greater than 75 μIU/mL after a low-dose oral sugar test.
- Study Design:
- Phase 1 (Study Period 1, SP1): A 20-week double-blind, randomized, placebo-controlled trial.
- Phase 2 (SP2): A subsequent 20-week open-label phase where all horses received velagliflozin.
- Groups:
- Placebo group: 19 horses received an inactive pill.
- Velagliflozin group: 18 horses received velagliflozin at 0.3 mg/kg orally every 24 hours.
- Measurements:
- Resting insulin, glucose, and triglyceride concentrations measured at intervals.
- Body condition score (BCS) assessed to monitor physical changes.
- Statistical Analysis:
- Comparison between groups and study periods using Mann-Whitney U test.
- Within SP1, changes over time assessed by generalized linear mixed effects models (GLMMs).
Results
- Insulin Concentrations:
- Velagliflozin group had significantly lower insulin concentrations during SP1: median 71 μIU/mL (IQR 33-131) versus placebo median 157 μIU/mL (IQR 82-298), p < 0.0001.
- The average reduction in insulin due to velagliflozin was approximately 155 μIU/mL (95% CI: 90-219).
- In SP2, horses initially receiving placebo experienced reductions in insulin levels after starting velagliflozin (median 50 μIU/mL, IQR 26-99), p < 0.0001.
- Triglycerides:
- All horses experienced a transient increase in serum triglyceride levels during velagliflozin treatment.
- No clinical abnormalities or adverse effects related to this increase were reported.
- Body Condition Score (BCS):
- Horses treated with velagliflozin lost more body condition compared to placebo during SP1.
- The median BCS decreased by 1 point from baseline in the velagliflozin group (p = 0.02), indicating mild weight loss or improvement in body fat.
Conclusions
- Velagliflozin effectively lowers resting insulin concentrations in horses with insulin dysregulation.
- The drug was well tolerated, with transient changes in triglycerides but no reported negative health effects.
- The reduction in body condition score suggests possible metabolic improvements alongside insulin reduction.
- Velagliflozin shows promise as a therapeutic agent for managing hyperinsulinemia in equine metabolic disease, but further research may be warranted to fully assess long-term safety and effects.
Cite This Article
APA
Thane K, Voth R, Klee R, Warnken T, Chukwu V, Frank N.
(2025).
Effects of the Sodium-Glucose Cotransporter-2 Inhibitor Velagliflozin on Insulin Concentrations in Horses With Insulin Dysregulation.
J Vet Intern Med, 39(6), e70256.
https://doi.org/10.1111/jvim.70256 Publication
Researcher Affiliations
- Cummings School of Veterinary Medicine, Tufts University, Grafton, Massachusetts, USA.
- Boehringer Ingelheim Animal Health USA, Duluth, Georgia, USA.
- Boehringer Ingelheim Vetmedica GmbH, Ingelheim am Rhein, Germany.
- Boehringer Ingelheim Vetmedica GmbH, Ingelheim am Rhein, Germany.
- Boehringer Ingelheim Animal Health USA, Duluth, Georgia, USA.
- College of Veterinary Medicine, Mississippi State University, Starkville, Mississippi, USA.
MeSH Terms
- Animals
- Female
- Male
- Blood Glucose / analysis
- Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
- Double-Blind Method
- Horse Diseases / drug therapy
- Horse Diseases / blood
- Horses
- Hyperinsulinism / veterinary
- Hyperinsulinism / drug therapy
- Insulin / blood
- Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
- Sodium-Glucose Transporter 2 Inhibitors / pharmacology
Grant Funding
- Boehringer Ingelheim Animal Health
Conflict of Interest Statement
Authors declare no off‐label use of antimicrobials. Nicholas Frank consults for, and Rebecca Voth, Rebecca Klee, Tobias. Warnken, and Victor Chukwi are employed by Boehringer Ingelheim, which provided funds to support this study.
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