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PloS one2018; 13(9); e0203655; doi: 10.1371/journal.pone.0203655

The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies.

Abstract: There are no registered veterinary drugs for treating insulin dysregulation and preventing insulin-associated laminitis in horses. Velagliflozin is a sodium-glucose co-transport 2 inhibitor that reduces renal glucose reabsorption, promotes glucosuria, and consequently, decreases blood glucose and insulin concentrations. This study aimed to determine if velagliflozin reduced hyperinsulinemia and prevented laminitis in insulin-dysregulated ponies fed a challenge diet high in non-structural carbohydrates (NSC). An oral glucose test (1 g dextrose/kg BW) was used to screen 75 ponies for insulin dysregulation, of which 49 ponies with the highest insulin concentrations were selected. These animals were assigned randomly to either a treated group (n = 12) that received velagliflozin (0.3 mg/kg BW, p.o., s.i.d.) throughout the study, or a control group (n = 37). All ponies were fed a maintenance diet of alfalfa hay for 3 weeks, before transferring to a challenge diet (12 g NSC/kg BW/d) for up to 18 d. Blood glucose and serum insulin concentrations were measured over 4 h after feeding, on d 2 of the diet. The maximum glucose concentration was 22% lower (P = 0.014) in treated animals, with a geometric mean (95% CI) of 9.4 (8.0-11.0) mM, versus 12.1 (10.7-13.7) mM in the controls. This was reflected by lower (45%) maximum insulin concentrations in the treated group (P = 0.017), of 149 (97-228) μIU/mL, versus 272 (207-356) μIU/mL for controls. The diet induced Obel grade 1 or 2 laminitis in 14 of the 37 controls (38%), whereas no velagliflozin-treated pony developed laminitis (P = 0.011). Velagliflozin was well-tolerated, with no hypoglycemia or any clinical signs of adverse effects. The main limitation of this study was the sample size. Velagliflozin shows promise as a safe and effective compound for treating insulin dysregulation and preventing laminitis by reducing the hyperinsulinemic response to dietary NSC.
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Publication Date: 2018-09-13 PubMed ID: 30212530PubMed Central: PMC6136744DOI: 10.1371/journal.pone.0203655Google Scholar: Lookup
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  • Clinical Trial
  • Veterinary
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

This research tests the effectiveness of the drug Velagliflozin in treating insulin dysregulation and preventing laminitis in ponies.

Objectives of the Study

  • The main aim of the research was to study the impact of Velagliflozin, a sodium-glucose co-transport 2 inhibitor, on insulin-dysregulated ponies.
  • The researchers aimed to see if this drug could reduce hyperinsulinemia (excess levels of insulin in the blood) and prevent laminitis (a severe and painful inflammatory condition affecting the horse’s hoof).

Methodology

  • An oral glucose test was conducted on 75 ponies to identify those with insulin dysregulation. Out of these, 49 ponies with the highest insulin concentrations were selected.
  • Among the selected group, 12 ponies were randomly chosen and treated with Velagliflozin, while the remaining 37 acted as control, receiving no treatment.
  • All ponies were initially fed an alfalfa hay diet for three weeks before switching to a high non-structural carbohydrate (NSC) diet for up to 18 days.
  • Blood glucose and serum insulin concentrations were measured after feeding, on the second day of the new diet.

Results of the Study

  • The maximum glucose concentration in the treated ponies was 22% lower compared to the control group.
  • The maximum insulin concentrations were also reduced by 45% in the treated group compared to controls.
  • In the control group, 14 out of 37 ponies developed Obel grade 1 or 2 laminitis, but none of the Velagliflozin-treated ponies developed this condition.

Conclusions and Limitations

  • Velagliflozin was found to be well-tolerated by the ponies, with no signs of hypoglycemia or any adverse effects.
  • This drug has potential as a safe and effective compound for treating insulin dysregulation and preventing laminitis in ponies.
  • The study conceded that a key limitation was the small sample size. More studies with a larger pool of subjects could offer more definitive conclusions.

Cite This Article

APA
Meier A, Reiche D, de Laat M, Pollitt C, Walsh D, Sillence M. (2018). The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies. PLoS One, 13(9), e0203655. https://doi.org/10.1371/journal.pone.0203655

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 13
Issue: 9
Pages: e0203655
PII: e0203655

Researcher Affiliations

Meier, Alexandra
  • Earth, Environmental and Biological Sciences School, Queensland University of Technology, Brisbane, Queensland, Australia.
Reiche, Dania
  • Boehringer Ingelheim Vetmedica, Ingelheim am Rhein, Germany.
de Laat, Melody
  • Earth, Environmental and Biological Sciences School, Queensland University of Technology, Brisbane, Queensland, Australia.
Pollitt, Christopher
  • Australian Equine Laminitis Research Unit, School of Veterinary Science, University of Queensland, St Lucia, Queensland, Australia.
Walsh, Donald
  • Animal Health Foundation, Pacific, Missouri, United States of America.
Sillence, Martin
  • Earth, Environmental and Biological Sciences School, Queensland University of Technology, Brisbane, Queensland, Australia.

MeSH Terms

  • Adrenocorticotropic Hormone / analysis
  • Animals
  • Blood Glucose / analysis
  • Body Weight / drug effects
  • Diet
  • Foot Diseases / pathology
  • Foot Diseases / prevention & control
  • Foot Diseases / veterinary
  • Glucose Tolerance Test
  • Hoof and Claw / pathology
  • Horse Diseases / drug therapy
  • Horse Diseases / pathology
  • Horses
  • Hyperinsulinism / drug therapy
  • Hyperinsulinism / pathology
  • Insulin / blood
  • Nitriles / pharmacology
  • Nitriles / therapeutic use
  • Random Allocation
  • Sodium-Glucose Transport Proteins / antagonists & inhibitors
  • Sodium-Glucose Transport Proteins / metabolism

Conflict of Interest Statement

The funders of this study have filed international patent applications on the use of SGLT2 inhibitors in horses: Boehringer Ingelheim Vetmedica GmbH, WO2014/161836 and WO2015/150299 entitled “Treatment of metabolic disorders in equine animals”. Boehringer Ingelheim is currently exploring the possibility of the commercial use of velagliflozin in horses. DR is an employee of Boehringer Ingelheim and is named as an inventor on the above patent. This does not alter our adherence to all PLOS ONE policies on sharing data and materials. All other authors have declared that no competing interests exist.

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Citations

This article has been cited 15 times.
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