Analyze Diet
Equine veterinary journal2026; doi: 10.1002/evj.70181

Short-term clinical responses in horses and ponies treated with canagliflozin: A clinical field study.

Abstract: Treatment with the sodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozin in insulin dysregulated (ID) horses has shown promising results in randomised clinical trials. Larger field studies are needed to further evaluate treatment responses and potential adverse effects under real-world conditions. Objective: To assess the short-term effects of canagliflozin on postprandial glucose and insulin responses in client-owned horses and ponies with ID using a single-sample feed-challenge test (FCT), and to characterise treatment-associated changes in bodyweight, liver enzyme activities, and triglyceride concentrations. Methods: Multicentre pre-post intervention study. Methods: Seventy privately owned horses and ponies with ID, confirmed by an oral sugar test, were enrolled. Horses received oral canagliflozin (0.4-0.6 mg/kg bwt once daily) for 3 weeks. Bodyweight, clinical biochemical parameters, and glucose and insulin concentrations from an FCT based on each horse's forage were obtained before and after treatment. Data were analysed using linear mixed-effects models. Results: The least squares (LS) means insulin concentrations (± SEM) during the FCT decreased from 304.4 ± 25.4 to 171.2 ± 25.9 μIU/mL after 3 weeks of treatment with canagliflozin (p < 0.001). Thirteen percent (9/70) of horses did not exhibit a reduction in insulin concentrations after treatment. The geometric LS means (95% confidence interval) triglyceride concentration (0.4 [0.3-0.5] vs. 1.2 [0.9-1.5] mmol/L; p < 0.001) and glutamate dehydrogenase (GLDH) activity (91 [73-112] vs. 152 [123-188] μkat/L; p 5.6 mmol/L) were observed in 9% (6/70) of treated horses. Conclusions: Absence of a placebo-treated control group. Conclusions: The postprandial insulin concentrations decreased in most canagliflozin treated horses, however, a subset failed to respond or developed marked increases in triglycerides. These findings underscore the need for careful monitoring of insulin response and lipid parameters during SGLT2 inhibitor therapy in horses.
Publication Date: 2026-05-10 PubMed ID: 42108673DOI: 10.1002/evj.70181Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

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.

Objective Overview

  • This study evaluated the short-term effects of canagliflozin, an SGLT2 inhibitor, on improving insulin regulation and metabolic parameters in insulin dysregulated horses and ponies under real-world clinical settings.
  • The research assessed changes in post-meal insulin and glucose levels, bodyweight, liver enzymes, and triglycerides over a 3-week treatment period.

Background and Rationale

  • Insulin dysregulation (ID) in horses and ponies is a significant health concern, often linked with laminitis and other metabolic disorders.
  • Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that reduces blood sugar by increasing glucose excretion through the urine.
  • Previous small randomized clinical trials indicated canagliflozin may lower insulin levels post-feeding in horses with ID, but larger, practical field studies are needed to assess effectiveness and safety.

Study Design and Methods

  • Multicentre pre-post intervention study involving 70 client-owned horses and ponies diagnosed with insulin dysregulation via an oral sugar test.
  • Participants received oral canagliflozin once daily (dosage 0.4-0.6 mg/kg bodyweight) for three weeks.
  • Pre- and post-treatment evaluations included:
    • Single-sample feed-challenge test (FCT) using each animal’s forage to measure postprandial (after meal) glucose and insulin concentrations.
    • Bodyweight measurements.
    • Clinical biochemical parameters including liver enzyme activities (especially glutamate dehydrogenase – GLDH) and blood triglyceride concentrations.
  • Data were statistically analyzed using linear mixed-effects models to assess changes attributable to treatment.

Key Results

  • Significant reduction in insulin levels during the FCT after three weeks of treatment:
    • Insulin concentrations decreased from an average of 304.4 ± 25.4 μIU/mL to 171.2 ± 25.9 μIU/mL (p < 0.001).
  • Approximately 13% of the horses (9 out of 70) did not show a reduction in insulin levels despite treatment.
  • Unexpected increases in blood triglyceride concentrations and liver enzyme (GLDH) activity were observed in some horses:
    • Triglycerides increased from an average of 0.4 (0.3-0.5) mmol/L to 1.2 (0.9-1.5) mmol/L (p < 0.001).
    • GLDH activity rose from 91 (73-112) to 152 (123-188) μkat/L (p < 0.001), indicating potential liver stress or damage.
  • These adverse metabolic changes, including marked hypertriglyceridemia (triglycerides > 5.6 mmol/L), were noted in about 9% (6/70) of treated horses.

Interpretation and Implications

  • The majority of treated horses showed improved insulin regulation with lower postprandial insulin concentrations, supporting canagliflozin’s potential as a therapeutic agent in insulin dysregulated equids.
  • However, a notable subset did not respond, highlighting variability in treatment efficacy among individuals.
  • The appearance of increased triglycerides and liver enzyme levels in some horses raises concerns about possible adverse effects of canagliflozin in this population.
  • These findings suggest a need for careful clinical monitoring of both insulin response and lipid/liver parameters when using SGLT2 inhibitors like canagliflozin in horses.
  • Not having a placebo control group is a limitation, meaning that some observed changes cannot be definitively attributed to the drug without further controlled trials.

Conclusions

  • Canagliflozin treatment effectively reduced postprandial insulin levels in most horses and ponies with insulin dysregulation in a real-world clinical setting.
  • There was individual variability in response with some non-responders and some animals experiencing elevated triglycerides and liver enzyme activity, which may indicate adverse metabolic effects.
  • Caution and thorough monitoring are necessary when utilizing SGLT2 inhibitors for managing insulin dysregulation in equine patients.
  • Further larger, placebo-controlled studies are warranted to fully establish safety and efficacy profiles of canagliflozin in this species.

Cite This Article

APA
Hällbom M, Lindåse ST, Wartel M, Bröjer J. (2026). Short-term clinical responses in horses and ponies treated with canagliflozin: A clinical field study. Equine Vet J. https://doi.org/10.1002/evj.70181

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Hällbom, Moa
  • Distriktsveterinärerna, The Swedish Board of Agricultural Science, Fjärdhundra, Sweden.
Lindåse, Sanna Truelsen
  • Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Wartel, Monika
  • Distriktsveterinärerna, The Swedish Board of Agricultural Science, Fjärdhundra, Sweden.
Bröjer, Johan
  • Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.

References

This article includes 32 references
  1. De Laat MA, McGowan CM, Sillence MN, Pollitt CC. Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses.. Equine Vet J 2010;42(2):129–135.
  2. Durham AE, Frank N, McGowan CM, Menzies‐Gow NJ, Roelfsema E, Vervuert I. ECEIM consensus statement on equine metabolic syndrome.. J Vet Intern Med 2019;33(2):335–349.
  3. 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.
  4. Kellon EM, Gustafson KM. Use of the SGLT2 inhibitor canagliflozin for control of refractory equine hyperinsulinemia and laminitis.. Open Vet J 2022;12(4):511–518.
  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;37(6):2520–2528.
  6. 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.
  7. Sundra T, Knowles E, Rendle D, Kelty E, Lester G, Rossi G. Short‐term clinical and biochemical responses following treatment with dapagliflozin or ertugliflozin in horses with hyperinsulinemia: a retrospective case series.. Domest Anim Endocrinol 2025;90:106894.
  8. 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 2023;35(6):311–320.
  9. 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;39(6):e70256.
  10. Kellon E, Gustafson K. Hypertriglyceridemia in equines with refractory hyperinsulinemia treated with SGLT2 inhibitors.. Open Vet J 2023;13(3):365–375.
  11. Dunkel B, Wilford SA, Parkinson NJ, Ward C, Smith P, Grahame L. Severe hypertriglyceridaemia in horses and ponies with endocrine disorders.. Equine Vet J 2014;46(1):118–122.
  12. Frank N, Elliott SB, Brandt LE, Keisler DH. Physical characteristics, blood hormone concentrations, and plasma lipid concentrations in obese horses with insulin resistance.. J Am Vet Med Assoc 2006;228(9):1383–1390.
  13. Saldanha IJ, Skelly AC, Ley KV, Wang Z, Berliner E, Bass EB. Inclusion of nonrandomized studies of interventions in systematic reviews of intervention effectiveness: an update (Report No. 22‐EHC033).. Rockville, MD: Agency for Healthcare Research and Quality (US); 2022.
  14. Black N. Why we need observational studies to evaluate the effectiveness of health care.. BMJ 1996;312(7040):1215–1218.
  15. 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(S1):64.
  16. Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between condition score, physical measurements and body fat percentage in mares.. Equine Vet J 1983;15(4):371–372.
  17. Carter RA, Geor RJ, Burton Staniar W, Cubitt TA, Harris PA. Apparent adiposity assessed by standardised scoring systems and morphometric measurements in horses and ponies.. Vet J 2009;179(2):204–210.
  18. Jansson A. Utfodringsrekommendationer för häst (Report No. 289).. Uppsala: Department of Animal Nutrition and Management; 2013.
  19. Karikoski NP, Box JR, Mykkänen AK, Kotiranta VV, Raekallio MR. Variation in insulin response to oral sugar test in a cohort of horses throughout the year and evaluation of risk factors for insulin dysregulation.. Equine Vet J 2022;54(5):905–913.
  20. Sibthorpe PEM, Fitzgerald DM, Chen L, Sillence MN, de Laat MA. A starch‐rich treat affects enteroinsular responses in ponies.. J Am Vet Med Assoc 2022;260(S3):94–101.
  21. Dowling RH. Glucagon‐like peptide‐2 and intestinal adaptation: an historical and clinical perspective.. J Nutr 2003;133(11):3703–3707.
  22. 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(5):513–519.
  23. Bröjer J. Short‐term effects of canagliflozin on beta‐cell function in horses with insulin dysregulation—preliminary results from an ongoing randomized, double‐blind, placebo‐controlled trial.. 5th Global Equine Endocrine Symposium Bern: Flemmkomm GmbH & CO; 2023.
  24. Zemek CHK, Kemp KL, Bertin FR. Value of measuring markers of lipid metabolism in horses during an oral glucose test.. J Vet Intern Med 2024;38(6):3309–3314.
  25. Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T. Metabolic response to sodium‐glucose cotransporter 2 inhibition in type 2 diabetic patients.. J Clin Invest 2014;124(2):499–508.
  26. Lundkvist P, Pereira MJ, Kamble PG, Katsogiannos P, Langkilde AM, Esterline R. Glucagon levels during short‐term SGLT2 inhibition are largely regulated by glucose changes in patients with type 2 diabetes.. J Clin Endocrinol Metab 2019;104(1):193–201.
  27. Merovci A, Solis‐Herrera C, Daniele G, Eldor R, Fiorentino TV, Tripathy D. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.. J Clin Invest 2014;124(2):509–514.
  28. Jeffcott L, Field J. Current concepts of hyperlipaemia in horses and ponies.. Vet Rec 1985;116(17):461–466.
  29. McKenzie HC. Equine Hyperlipidemias.. Vet Clin North Am Equine Pract 2011;27(1):59–72.
  30. Veterinary Medicines Directorate. Calculation of adverse event incidence for veterinary medicines [Internet].. GOV.UK 2025 [cited 2026.02.08].
  31. Michanek P, Bröjer J, Lilliehöök I, Fjordbakk CT, Löwgren M, Hedeland M. Pharmacokinetics and alterations in glucose and insulin levels after a single dose of canagliflozin in healthy Icelandic horses. J Vet Pharm Ther 2025;48(S1):41–49.
  32. Michanek P, Bröjer J, Lilliehöök I, Fjordbakk C, Erkas M, Löwgren M. Canagliflozin: pharmacokinetics, tolerability and glucose/insulin effects of supratherapeutic doses in healthy horses. Vet J 2025;313:106412.

Citations

This article has been cited 0 times.