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Open veterinary journal2022; 12(4); 511-518; doi: 10.5455/OVJ.2022.v12.i4.14

Use of the SGLT2 inhibitor canagliflozin for control of refractory equine hyperinsulinemia and laminitis.

Abstract: Hyperinsulinemia associated with pituitary pars intermedia dysfunction (PPID) and/or equine metabolic syndrome is well documented to put horses at high risk of laminitis. While dietary control of simple sugars and starch is the most effective therapy to control hyperinsulinemia, some horses fail to respond. Ten horses with hyperinsulinemia refractory to diet control, metformin, levothyroxine, and pergolide (if diagnosed with PPID) were treated with sodium-glucose cotransporter-2 inhibitor canagliflozin (Invokana®). Nine horses were hyperglycemic (>5.5 mmol/l) or had a history of hyperglycemia. Before instituting therapy, renal function was assessed by determining serum creatinine and blood urea nitrogen concentrations. Canagliflozin was administered orally once a day, with food. Dipstick urinalysis was performed every 2 weeks to confirm glucosuria and screen for proteinuria. Owners were also instructed regarding clinical signs consistent with urinary tract infection. All horses responded with a substantial decrease in serum insulin concentrations to normal or near normal values. Laminitis pain resolved in all cases, with regression of fat deposits. Owner satisfaction with outcomes was 100%. Once daily administration of the SGLT2 inhibitor canagliflozin corrected hyperglycemia, reduced insulin to normal or near normal levels, and was 100% effective in reversing or reducing abnormal fat pads and eliminating laminitis pain in horses with refractory hyperinsulinemia and laminitis. The core aspects of therapy-diet control, exercise when possible, and adequate treatment of PPID-must also be maintained if using canagliflozin. Canagliflozin should be reserved for refractory cases. Further controlled trials to investigate canagliflozin pharmacokinetics, pharmacodynamics, efficacy, and safety are needed.
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Publication Date: 2022-08-07 PubMed ID: 36118716PubMed Central: PMC9473365DOI: 10.5455/OVJ.2022.v12.i4.14Google 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.

This research investigates the use of canagliflozin, a SGLT2 inhibitor, to treat hyperinsulinemia and laminitis in horses. The study found a significant decrease in serum insulin levels, elimination of laminitis pain, and high owner satisfaction, suggesting the potential of canagliflozin as an effective control method for these conditions in horses.

Horse Conditions and Previous Treatment Methods

  • Hyperinsulinemia is a condition in horses typically associated with pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome. These conditions put horses at significant risk of laminitis, a painful and debilitating inflammatory condition of the hoof.
  • Typically, the most effective treatment to control hyperinsulinemia is dietary control specifically geared towards regulating sugars and starch. However, certain horses do not respond to this treatment, thus requiring other intervention methods.
  • Prior to this study, horses who were found to be unresponsive to diet control were treated using drugs such as metformin, levothyroxine, and pergolide. Continued lack of response prompted the researchers to try using canagliflozin, a drug primarily used for human diabetes treatment.

Use of Canagliflozin in the Study

  • The study involved ten horses, out of which nine had hyperglycemia or a history of the condition.
  • Before commencing canagliflozin treatment, the renal function of the horses was assessed via measurement of serum creatinine and blood urea nitrogen concentrations.
  • The canagliflozin treatment was delivered orally once a day alongside food. The effectiveness of the treatment was gauged by conducting a dipstick urinalysis every two weeks to observe glucosuria and screen for proteinuria.
  • Horse owners were also trained to observe and report clinical signs associated with urinary tract infections as a precautionary measure against potential side effects of canagliflozin.

Results and Future Research

  • The results of the study were very encouraging. All horses showed significant decreases in serum insulin concentrations, successfully bringing them down to near-normal levels. In addition, pain related to laminitis resolved for all horses and there was a noticeable regression of fat deposits.
  • The study also found that canagliflozin was effective in correcting hyperglycemia, reducing insulin to normal or near-normal levels, reversing or reducing abnormal fat pads, and eliminating laminitis pain in horses with refractory hyperinsulinemia and laminitis.
  • Going forward, researchers will have to investigate the pharmacokinetics, pharmacodynamics, efficacy, and safety of canagliflozin in horses, to further establish its potential as an effective treatment method for hyperinsulinemia and laminitis.

Cite This Article

APA
Kellon EM, Gustafson KM. (2022). Use of the SGLT2 inhibitor canagliflozin for control of refractory equine hyperinsulinemia and laminitis. Open Vet J, 12(4), 511-518. https://doi.org/10.5455/OVJ.2022.v12.i4.14

Publication

Open veterinary journal
ISSN: 2218-6050
NlmUniqueID: 101653182
Country: Libya
Language: English
Volume: 12
Issue: 4
Pages: 511-518

Researcher Affiliations

Kellon, Eleanor M
  • Equine Cushing's and Insulin Resistance Group, Inc. 2307 Rural Road, Tempe, AZ 85282 USA.
Gustafson, Kathleen M
  • Equine Cushing's and Insulin Resistance Group, Inc. 2307 Rural Road, Tempe, AZ 85282 USA.

MeSH Terms

  • Animals
  • Canagliflozin / therapeutic use
  • Creatinine / therapeutic use
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / veterinary
  • Glucose / metabolism
  • Glucose / therapeutic use
  • Horse Diseases / drug therapy
  • Horses
  • Hyperglycemia / complications
  • Hyperglycemia / veterinary
  • Hyperinsulinism / complications
  • Hyperinsulinism / drug therapy
  • Hyperinsulinism / veterinary
  • Insulin
  • Metformin / therapeutic use
  • Monosaccharides / therapeutic use
  • Pain / complications
  • Pain / veterinary
  • Pergolide / therapeutic use
  • Pituitary Diseases / complications
  • Pituitary Diseases / veterinary
  • Sodium / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • Starch / therapeutic use
  • Thyroxine

Conflict of Interest Statement

The authors declare that there is no conflict of interest.

References

This article includes 18 references
  1. Chameroy K.A.. Diagnosis and management of horses with equine metabolic syndrome (EMS). 2010 University of Tennessee, Knoxville, TN.
  2. de Laat M.A, McGowan C.M, Sillence M.N, Pollitt C.C. Hyperinsulinemic laminitis. Vet. Clin. North. Am. Equine Pract. 2010;26(2):257–264.
    pubmed: 20699173
  3. Durham A.E.. Therapeutics for equine endocrine disorders. Vet. Clin. North. Am. Equine Pract. 2017;33(1):127–139.
    pubmed: 28190613
  4. Durham A.E, Hughes K.J, Cottle H.J, Rendle D.I, Boston R.C. Type 2 diabetes mellitus with pancreatic beta cell dysfunction in 3 horses confirmed with minimal model analysis. Equine. Vet. J. 2009;41(9):924–929.
    pubmed: 20383993
  5. Durham A.E, Rendle D.I, Newton J.E. The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance. Equine. Vet. J. 2008;40(5):493–500.
    pubmed: 18482898
  6. Johnson P.J, Messer N.T, Kellon E. Treatment of equine metabolic syndrome. Compend. Cont. Educ. Pract. Vet. 2004;26(2):122–130.
  7. Kellon E.M.. Tiered management approach to EMS and PPID. In Proceedings of the 2017 NO Laminitis Conference; 2017; Tucson, AZ.
  8. Knopp J.L, Holder-Pearson L, Chase J.G. Insulin units and conversion factors: a story of truth, boots, and faster half-truths. J. Diabetes. Sci. Technol. 2019;13(3):597–600.
    pmc: PMC6501531pubmed: 30318910
  9. Lega I.C, Bronskill S.E, Campitelli M.A, Guan J, Stall N.M, Lam K, McCarthy L.M, Gruneir A, Rochon P.A. Sodium glucose cotransporter 2 inhibitors and risk of genital mycotic and urinary tract infection: A population-based study of older women and men with diabetes. Diabetes. Obes. Metab. 2019;21(11):2394–2404.
    pubmed: 31264755
  10. Meier A, Reiche D, de Laat M, Pollitt C, Walsh D, Sillence M. The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies. PLoS One 2018;13(9):e0203655.
    pmc: PMC6136744pubmed: 30212530
  11. Meier A, de Laat M, Reiche D, Fitzgerald D, Sillence M. The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies. BMC. Vet. Res. 2019;15(1):65.
    pmc: PMC6390376pubmed: 30808423
  12. Menzies-Gow N.J.. Endocrinopathic laminitis: reducing the risk through diet and exercise. Vet. Clin. North. Am. Equine Pract. 2010;26(2):371–378.
    pubmed: 20699181
  13. Morgan R.A, Keen J.A, McGowan C.M. Treatment of equine metabolic syndrome: a clinical case series. Equine. Vet. J. 2016;48(4):422–426.
    pubmed: 25808563
  14. Patterson-Kane J.C, Karikoski N.P, McGowan C.M. Paradigm shifts in understanding equine laminitis. Vet. J. 2018;231:33–40.
    pubmed: 29429485
  15. Perlman A, Heyman S.N, Matok I, Stokar J, Muszkat M, Szalat A. Acute renal failure with sodium-glucose-cotransporter-2 inhibitors: analysis of the FDA adverse event report system database. Nutr. Metab. Cardiovasc. Dis. 2017;27(12):1108–1113.
    pubmed: 29174031
  16. Rendle D.I, Rutledge F, Hughes K.J, Heller J, Durham A.E. Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses. Equine. Vet. J. 2013;45(6):751–754.
    pubmed: 23600690
  17. Ryan P.B, Buse J.B, Schuemie M.J, DeFalco F, Yuan Z, Stang P.E, Berlin J.A, Rosenthal N. Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real-world meta-analysis of 4 observational databases (OBSERVE-4D). Diabetes. Obes. Metab. 2018;20(11):2585–2597.
    pmc: PMC6220807pubmed: 29938883
  18. Szalat A, Perlman A, Muszkat M, Khamaisi M, Abassi Z, Heyman S.N. Can SGLT2 inhibitors cause acute renal failure? plausible role for altered glomerular hemodynamics and medullary hypoxia. Drug. Saf. 2018;41(3):239–252.
    pubmed: 28952138

Citations

This article has been cited 7 times.
  1. Anger-Håål C, Fjordbakk CT, Ekstrand C, Skedsmo FS, Rørtveit R. Sodium-glucose transporters SGLT1 and SGLT2 in equine renal, hepatic and pancreatic tissue. BMC Vet Res 2025 Dec 17;22(1):36.
    doi: 10.1186/s12917-025-05173-1pubmed: 41408266google scholar: lookup
  2. Thane K, Voth R, Klee R, Warnken T, Chukwu V, Frank N. Effects of the Sodium-Glucose Cotransporter-2 Inhibitor Velagliflozin on Insulin Concentrations in Horses With Insulin Dysregulation. J Vet Intern Med 2025 Nov-Dec;39(6):e70256.
    doi: 10.1111/jvim.70256pubmed: 41063501google scholar: lookup
  3. Michanek P, Bröjer J, Lilliehöök I, Fjordbakk CT, Löwgren M, Hedeland M, Bergquist J, Ekstrand C. Pharmacokinetics and Alterations in Glucose and Insulin Levels After a Single Dose of Canagliflozin in Healthy Icelandic Horses. J Vet Pharmacol Ther 2025 Jan;48 Suppl 1(Suppl 1):41-49.
    doi: 10.1111/jvp.13476pubmed: 39113254google scholar: lookup
  4. Menzies-Gow NJ, Knowles EJ. Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses. J Vet Pharmacol Ther 2025 Jan;48 Suppl 1(Suppl 1):31-40.
    doi: 10.1111/jvp.13470pubmed: 38984777google scholar: lookup
  5. Lindåse S, Nostell K, Forslund A, Bergsten P, Bröjer J. Short-term effects of canagliflozin on glucose and insulin responses in insulin dysregulated horses: A randomized, placebo-controlled, double-blind, study. J Vet Intern Med 2023 Nov-Dec;37(6):2520-2528.
    doi: 10.1111/jvim.16906pubmed: 37864426google scholar: lookup
  6. Cahyaningrum A, Rahayu M, Rudijanto A, Handayani D. Effects of Lombok Island's local moringa (Moringa oleifera) leaf powder on the decrease of liver fructose levels and GLUT5 expression in albino rats (Rattus novergicus) fed a high fructose diet. Open Vet J 2023 May;13(5):532-540.
    doi: 10.5455/OVJ.2023.v13.i5.5pubmed: 37304614google scholar: lookup
  7. Kellon EM, Gustafson KM. Hypertriglyceridemia in equines with refractory hyperinsulinemia treated with SGLT2 inhibitors. Open Vet J 2023 Mar;13(3):365-375.
    doi: 10.5455/OVJ.2023.v13.i3.14pubmed: 37026076google scholar: lookup
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