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BMC veterinary research2019; 15(1); 65; doi: 10.1186/s12917-019-1811-2

The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies.

Abstract: A previous six-week (wk) study demonstrated the potential of the sodium-glucose linked transport inhibitor velagliflozin as a novel treatment for equine insulin dysregulation. The present study examined the safety and efficacy of velagliflozin over 16 wk. of treatment, and over 4 wk. of withdrawal. Twenty-four insulin dysregulated ponies were selected, based on their hyper-responsiveness to a diet challenge meal containing 3.8 g non-structural carbohydrates (NSC)/kg bodyweight (BW). Ponies with serum insulin > 90 μIU/mL either 2 or 4 h after feeding were enrolled, and randomly allocated to receive either velagliflozin (0.3 mg/kg BW orally once daily, n = 12), or a placebo (n = 10-12) for 16 wk. The subjects were fed 7.5 g NSC/kg BW/day to maintain a fat body condition. Safety was assessed through daily monitoring, veterinary examination, and the measurement of fasting blood glucose, biochemistry and haematology. Efficacy at reducing post-prandial hyperinsulinemia was assessed using a diet challenge every 8 wk. during treatment and 4 wk. after withdrawal. Results: Velagliflozin was well accepted by all subjects and caused no adverse effects or hypoglycaemia. Post-prandial serum insulin (insulin Cmax) did not change significantly in the control animals over the entire study period (P = 0.101). In contrast, insulin Cmax (mean ± SE) concentrations fell over time in the velagliflozin-treated group from 205 ± 25 μIU/mL in wk. 0, to 119 ± 19 μIU/mL (P = 0.015) and 117 ± 15 μIU/ml (P = 0.029) after 8 and 16 wk. of treatment, respectively. Although the insulin Cmax in this group was not significantly lower than in controls at wk-8 (P = 0.061), it was lower at wk-16 (P = 0.003), and all 12 treated ponies were below the previously-determined risk threshold for laminitis at this time. After 4 wk. withdrawal, the insulin Cmax returned to 199 ± 36 μIU/mL in the treated group, with no rebound effect. Conclusions: Velagliflozin appears to be a promising and safe treatment for equine insulin dysregulation, bringing post-prandial insulin concentrations below the laminitis risk threshold, albeit without normalising them.
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Publication Date: 2019-02-26 PubMed ID: 30808423PubMed Central: PMC6390376DOI: 10.1186/s12917-019-1811-2Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research presents a 16-week study investigating the safety and efficacy of velagliflozin as a treatment for insulin dysregulation in ponies. The results suggest that velagliflozin may be a safe and promising option, with the capacity to reduce insulin concentrations below the laminitis risk level.

Research Study Overview

  • The study seeks to explore the effectiveness of a sodium-glucose linked transport inhibitor known as velagliflozin as a treatment for equine insulin dysregulation over a period of 16 weeks, including 4 weeks of withdrawal.
  • 24 ponies exhibiting insulin dysregulation, defined by a heightened response to a diet challenge meal loaded with 3.8g non-structural carbohydrates (NSCs) per kilogram of body weight, were chosen for the study.

Research Methodology

  • Selection of ponies was based on serum insulin levels greater than 90μIU/mL either 2 or 4 hours after feeding.
  • Ponies were then randomly divided into two groups with one group receiving velagliflozin (0.3 mg/kg BW distributed orally once daily) and the other group given a placebo for a span of 16 weeks.
  • All ponies were fed 7.5g NSC/kg BW/day to maintain a fat body condition.
  • The study evaluated the safety of the drug through daily monitoring, veterinary checks, and measurements of fasting blood glucose, biochemistry, and haematology.
  • Velagliflozin’s effectiveness in decreasing post-prandial hyperinsulinemia was measured through a dietary challenge every 8 weeks during treatment and 4 weeks after withdrawal.

Results of the Study

  • The results demonstrated that all subjects adjusted well to velagliflozin with no hypoglycaemia or negative side effects being reported.
  • Post-prandial serum insulin in the control group remained consistent throughout the research period (P=0.101).
  • In contrast, the velagliflozin-treated group showed a decrease in insulin concentrations from 205 ± 25 μIU/mL in week 0, to 119 ± 19 μIU/mL (P=0.015) and 117 ± 15 μIU/ml (P=0.029) after 8 weeks and 16 weeks of treatment, respectively.
  • Though not significantly lower than the control group’s measurements at week-8 (P=0.061), the levels were lower at week-16 (P=0.003), with all velagliflozin-treated ponies dropping below the pre-determined laminitis risk threshold.
  • After 4 weeks of withdrawal, the velagliflozin-treated group showed an insulin measurement of 199 ± 36 μIU/mL with no rebound effect.

Conclusion

  • The research concludes that velagliflozin is a promising and safe treatment for equine insulin dysregulation.
  • While the treatment doesn’t normalize insulin levels, it does reduce insulin concentrations below the danger zone for laminitis.

Cite This Article

APA
Meier A, de Laat M, Reiche D, Fitzgerald D, Sillence M. (2019). The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies. BMC Vet Res, 15(1), 65. https://doi.org/10.1186/s12917-019-1811-2

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 15
Issue: 1
Pages: 65

Researcher Affiliations

Meier, A
  • Earth, Environmental and Biological Sciences School, Queensland University of Technology (QUT), Brisbane, Queensland, 4000, Australia.
de Laat, M
  • Earth, Environmental and Biological Sciences School, Queensland University of Technology (QUT), Brisbane, Queensland, 4000, Australia.
Reiche, D
  • Boehringer Ingelheim Vetmedica, 55218, Ingelheim am Rhein, Germany.
Fitzgerald, D
  • Earth, Environmental and Biological Sciences School, Queensland University of Technology (QUT), Brisbane, Queensland, 4000, Australia.
Sillence, M
  • Earth, Environmental and Biological Sciences School, Queensland University of Technology (QUT), Brisbane, Queensland, 4000, Australia. martin.sillence@qut.edu.au.

MeSH Terms

  • Animals
  • Horse Diseases / blood
  • Horse Diseases / drug therapy
  • Horses
  • Hyperinsulinism / blood
  • Hyperinsulinism / drug therapy
  • Hyperinsulinism / veterinary
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Nitriles / therapeutic use
  • Random Allocation
  • Treatment Outcome

Grant Funding

  • na / Boehringer Ingelheim

Conflict of Interest Statement

ETHICS APPROVAL: This study was approved by the Animal Care and Ethics Committees of Queensland University of Technology (1500000204) and The University of Queensland (QUT/SVS/470/14). All procedures were conducted in accordance with the Australian Code for the Care and Use of Animals for Scientific Purposes (NHMRC, 8th edition, 2013). All animals used in the study were owned by Queensland University of Technology and were used with the consent of the University. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: DR is an employee of the company that funded this research: Boehringer-Ingelheim. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Citations

This article has been cited 8 times.
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