Short-term effects of canagliflozin on glucose and insulin responses in insulin dysregulated horses: A randomized, placebo-controlled, double-blind, study.
Abstract: Decreasing hyperinsulinemia is crucial in preventing laminitis in insulin dysregulated (ID) horses. Complementary pharmacological treatments that efficiently decrease postprandial hyperinsulinemia in ID horses are needed. Objective: Compare short-term effects of canagliflozin vs placebo on glucose and insulin responses to an oral sugar test (OST) as well as the effects on body weight and triglyceride concentrations in horses with ID. Methods: Sixteen privately-owned ID horses. Methods: A single-center, randomized, double-blind, placebo-controlled, parallel design study. The horses were randomized (ratio 1:1) to either once daily PO treatment with 0.6 mg/kg canagliflozin or placebo. The study consisted of an initial 3-day period for obtaining baseline data, a 3-week double-blind treatment period at home, and a 3-day follow-up period similar to the initial baseline period but with continued double-blind treatment. Horses were subjected to an 8-sample OST in the morning of the third day on both visits. Results: Maximal geometric least square (LS) mean insulin concentration (95% confidence interval [CI]) during the OST decreased after 3 weeks of canagliflozin treatment compared with placebo (83.2; 55.4-125.0 vs 215.2; 143.2-323.2 μIU/mL). The geometric LS mean insulin response (insulin AUC0-180 ) for canagliflozin-treated horses was >66% lower compared with placebo. Least square mean body weight decreased by 11.1 (4-18.1) kg and LS mean triglyceride concentrations increased by 0.99 (0.47-1.5) mmol/L with canagliflozin treatment. Conclusions: Canagliflozin is a promising drug for treatment of ID horses that requires future studies.
© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Publication Date: 2023-10-21 PubMed ID: 37864426PubMed Central: PMC10658518DOI: 10.1111/jvim.16906Google Scholar: Lookup
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- Randomized Controlled Trial
- Veterinary
- Journal Article
Summary
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This study investigates the short-term effects of canagliflozin, a drug used to treat diabetes in humans, on horses with insulin dysregulation. Results suggest that canagliflozin significantly lowers insulin levels and body weight in these horses, suggesting its potential as a treatment.
Research Objectives
The primary objective of this study was to evaluate the effects of canagliflozin on horses affected by insulin dysregulation (ID). Researchers wanted to see if the drug, commonly used to treat diabetes in humans, could reduce hyperinsulinemia – an excess of insulin in the blood – which is a key concern in the prevention of laminitis in horses.
- The researchers sought to compare the effects of canagliflozin with a placebo on glucose and insulin responses in horses.
- They also aimed to observe any impact the drug might have on the body weight and triglyceride concentrations of the horses.
Research Design and Methods
Sixteen privately-owned horses with ID participated in this double-blind, placebo-controlled study. The design of the study was such that neither the researchers nor participants knew which horses were receiving the drug and which were given a placebo.
- The horses were divided into two groups – one received 0.6 mg/kg of canagliflozin orally per day, while the other group served as a control and received a placebo.
- The study comprised of an initial 3-day baseline data collection period, followed by a 3-week treatment period, and concluding with a 3-day follow-up period during which the treatment continued while further data was collected.
- To monitor changes, an oral sugar test was conducted on the third day of both the initial and final data collection periods.
Results of the Study
The study found that canagliflozin significantly reduced the insulin levels in horses with ID.
- Horses treated with canagliflozin showed a decrease in the insulin concentration as compared to those on the placebo, with average levels being over 66% lower.
- The horses receiving canagliflozin also lost weight, with an average drop of around 11.1 kg noted.
- However, canagliflozin treatment resulted in an increase in the concentration of triglycerides in the blood.
Conclusion
This study suggests that canagliflozin is a promising drug for the treatment of horses with ID. It was able to significantly reduce insulin levels and led to weight loss. However, the implication of increased triglyceride levels upon treatment with the drug needs to be further researched. Potential long-term effects and optimum dosage also require additional studies.
Cite This Article
APA
Lindåse S, Nostell K, Forslund A, Bergsten P, Bröjer J.
(2023).
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, 37(6), 2520-2528.
https://doi.org/10.1111/jvim.16906 Publication
Researcher Affiliations
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
- Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
MeSH Terms
- Animals
- Horses
- Canagliflozin / pharmacology
- Blood Glucose
- Insulin / blood
- Hyperinsulinism / drug therapy
- Hyperinsulinism / veterinary
- Horse Diseases / drug therapy
- Triglycerides / blood
- Body Weight
- Male
- Female
Grant Funding
- H-19-47-479 / The Swedish-Norwegian Foundation for Equine Research
Conflict of Interest Statement
Authors declare no conflict of interest.
References
This article includes 32 references
- Carslake H, Argo CM, Pinchbeck G. Insulinaemic and glycaemic responses to three forages in ponies.. Vet J 2018;235:83‐89.
- Lindåse S, Nostell K, Söder J, Bröjer J. Relationship between β‐cell response and insulin sensitivity in horses based on the oral sugar test and the euglycemic hyperinsulinemic clamp.. J Vet Intern Med 2017;31:1541‐1550.
- Patterson‐Kane JC, Karikoski NP, McGowan CM. Paradigm shifts in understanding equine laminitis.. Vet J 2018;231:33‐40.
- Durham AE, Frank N, McGowan CM. ECEIM consensus statement on equine metabolic syndrome.. J Vet Intern Med 2019;33:335‐349.
- Legere RM, Taylor DR, Davis JL. Pharmacodynamic effects of pioglitazone on high molecular weight adiponectin concentrations and insulin response after oral sugar in equids.. J Equine Vet 2019;82:102797.
- Tinworth KD, Boston RC, Harris PA, Sillence MN, Raidal SL, Noble GK. The effect of oral metformin on insulin sensitivity in insulin‐resistant ponies.. Vet J 2012;191:79‐84.
- Colmer SF, Adams AA, Adam E. The effect of pre‐dosing with metformin on the insulin response to oral sugar in insulin‐dysregulated horses.. Equine Vet J 2023.
- Deeks ED, Scheen AJ. Canagliflozin: a review in type 2 diabetes.. Drugs 2017;77:1577‐1592.
- Martinez R, Al‐Jobori H, Ali AM. Endogenous glucose production and hormonal changes in response to Canagliflozin and Liraglutide combination therapy.. Diabetes 2018;67:1182‐1189.
- 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:e0203655.
- 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;15:65.
- Lindåse S, Nostell K, Bröjer J. A modified oral sugar test for evaluation of insulin and glucose dynamics in horses.. Acta Vet Scand 2016;58(Suppl 1):64.
- Öberg J, Bröjer J, Wattle O, Lilliehöök I. Evaluation of an equine‐optimized enzyme‐linked immunosorbent assay for serum insulin measurement and stability study of equine serum insulin.. Comp Clin Path 2012;21:1291‐1300.
- Slough T, Gunkel C, Murray L. A comparison of methodologies for measuring glucose concentrations in the horse.. Prof Anim Sci 2011;27:204‐214.
- Allison DB, Paultre F, Maggio C, Mezzitis N, Pi‐Sunyer FX. The use of areas under curves in diabetes research.. Diabetes Care 1995;18:245‐250.
- Hannon TS, Kahn SE, Utzschneider KM. Review of methods for measuring β‐cell function: design considerations from the restoring insulin secretion (RISE) consortium.. Diabetes Obes Metab 2018;20:14‐24.
- Utzschneider KM, Prigeon RL, Faulenbach MV. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2‐h glucose levels.. Diabetes Care 2009;32:335‐341.
- Utzschneider KM, Younes N, Rasouli N. Shape of the OGTT glucose response curve: relationship with β‐cell function and differences by sex, race, and BMI in adults with early type 2 diabetes treated with metformin.. BMJ Open Diabetes Res Care 2021;9:e002264.
- Vickers AJ, Altman DG. Analysing controlled trials with baseline and follow up measurements.. BMJ 2001;323:1123‐1124.
- Kellon EM, Gustafson KM. Use of the SGLT2 inhibitor canagliflozin for control of refractory equine hyperinsulinemia and laminitis.. Open Vet J 2022;12:511‐518.
- Sundra T, Kelty E, Rendle D. Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: a case series.. Equine Vet Educ 2022;35:311‐320.
- Abdul‐Ghani MA, Norton L, Defronzo RA. Role of sodium‐glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes.. Endocr Rev 2011;32:515‐531.
- Nauck MA. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes.. Drug des Devel Ther 2014;8:1335‐1380.
- Rahmoune H, Thompson PW, Ward JM, Smith CD, Hong G, Brown J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non‐insulin‐dependent diabetes.. Diabetes 2005;54:3427‐3434.
- Komoroski B, Vachharajani N, Feng Y, Li L, Kornhauser D, Pfister M. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus.. Clin Pharmacol Ther 2009;85:513‐519.
- Hoenig M, Clark M, Schaeffer DJ, Reiche D. Effects of the sodium‐glucose cotransporter 2 (SGLT2) inhibitor velagliflozin, a new drug with therapeutic potential to treat diabetes in cats.. J Vet Pharmacol Ther 2018;41:266‐273.
- List JF, Whaley JM. Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans.. Kidney Int Suppl 2011;2011:S20‐S27.
- Nostell K, Lindåse S, Edberg H, Bröjer J. The effect of insulin infusion on heart rate and systemic blood pressure in horses with equine metabolic syndrome.. Equine Vet J 2019;51:733‐737.
- Al Jobori H, Daniele G, Adams J. Empagliflozin treatment is associated with improved β‐cell function in type 2 diabetes mellitus.. J Clin Endocrinol Metab 2018;103:1402‐1407.
- Shyr ZA, Yan Z, Ustione A, Egan EM, Remedi MS. SGLT2 inhibitors therapy protects glucotoxicity‐induced β‐cell failure in a mouse model of human KATP‐induced diabetes through mitigation of oxidative and ER stress.. PloS One 2022;17:e0258054.
- de Laat MA, Fitzgerald DM. Equine metabolic syndrome: role of the enteroinsular axis in the insulin response to oral carbohydrate.. Vet J 2023;294:105967.
- Pereira MJ, Lundkvist P, Kamble PG. A randomized controlled trial of dapagliflozin plus once‐weekly exenatide versus placebo in individuals with obesity and without diabetes: metabolic effects and markers associated with bodyweight loss.. Diabetes Ther 2018;9:1511‐1532.
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