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.
Publication Date: 2022-08-07 PubMed ID: 36118716PubMed Central: PMC9473365DOI: 10.5455/OVJ.2022.v12.i4.14Google Scholar: Lookup
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Summary
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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
Researcher Affiliations
- Equine Cushing's and Insulin Resistance Group, Inc. 2307 Rural Road, Tempe, AZ 85282 USA.
- 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.
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This article includes 18 references
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