Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses.
Abstract: Metformin is a potential therapeutic agent for the treatment of insulin resistance (IR). In laboratory animals, orally administered metformin reduces intestinal glucose absorption and may therefore affect insulinaemic responses to oral carbohydrate ingestion. Objective: To determine whether pretreatment with metformin reduces plasma glucose concentration and insulin responses following consumption of dextrose in horses. Methods: Therapeutic cross-over study. Methods: Seven healthy Standardbred and Thoroughbred geldings were subjected to an oral dextrose challenge test on 4 occasions: with and without metformin, before and after induction of IR with dexamethasone. Metformin was administered by nasogastric tube at 30 mg/kg bwt 1 h before administration of dextrose. Glucose and insulin concentrations in plasma/serum were measured at regular intervals during each test. Linear mixed models were specified for each predetermined outcome variable, and for each model the 'treatment' was included as a fixed effect with 4 categorical levels (none, metformin, dexamethasone and dexamethasone with metformin) and horse accounted for as a random effect. Results: In healthy horses, the administration of metformin resulted in a statistically significant reduction in peak glucose concentration (P = 0.002), area under the glucose curve (P<0.001) and insulin concentration 120 min after dextrose administration (P = 0.011). Following the induction of IR, administration of metformin was associated with significant differences in peak glucose concentration (P<0.001), the percentage increase in glucose concentration (P = 0.010), the area under the glucose curve (P<0.001) and insulin concentration at 120 min (P = 0.034) and 150 min after dextrose administration (P = 0.014). Conclusions: Metformin resulted in reduced glycaemic and insulinaemic responses both in healthy horses and in horses with experimentally induced IR. Conclusions: Metformin may benefit horses with naturally acquired IR by reducing glycaemic and insulinaemic responses to dietary nonstructural carbohydrates. Further investigations into the mechanisms of action of metformin in horses and controlled clinical trials are warranted.
© 2013 EVJ Ltd.
Publication Date: 2013-04-22 PubMed ID: 23600690DOI: 10.1111/evj.12068Google Scholar: Lookup
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- Clinical Trial
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates the impacts of the drug metformin on plasma glucose concentration and insulin responses following consumption of dextrose in horses. The study found that metformin significantly reduced glycemic and insulinaemic responses, both in healthy horses and in horses with induced insulin resistance.
Research Methodology
- Seven healthy Standardbred and Thoroughbred geldings participated in this study. The researchers carried out an oral dextrose challenge test on each horse four times, under different circumstances: without any treatment, with metformin alone, after inducing insulin resistance with dexamethasone, and with metformin after inducing insulin resistance.
- The administration of metformin, at a dosage of 30 mg/kg body weight, was done via a nasogastric tube one hour prior to providing the dextrose to the horses.
- Glucose and insulin concentrations in the horses’ plasma/serum were measured at regular intervals during each test.
- For the statistical analysis, the researchers used linear mixed models for each predetermined outcome variable. In each model, the ‘treatment’ was included as a fixed effect with four categorical levels, namely none, metformin, dexamethasone, and dexamethasone with metformin. The horse variable was accounted for as a random effect.
Key Findings
- In healthy horses, the use of metformin led to a significant decrease in peak glucose concentration, area under the glucose curve, and insulin concentration 120 minutes post dextrose administration.
- Once insulin resistance was induced, using metformin resulted in significant differences in peak glucose concentration, the percentage increase in glucose concentration, the area under the glucose curve, and insulin concentration at 120 and 150 minutes after administering dextrose.
Implications and Future Directions
- Metformin appears to significantly reduce glycemic and insulinaemic responses, in both healthy horses and those with insulin resistance produced in a laboratory setting. Therefore, metformin might be beneficial for horses with naturally acquired insulin resistance, by minimizing glycemic and insulinaemic responses to nonstructural carbohydrates in their diet.
- The authors suggest that further research is necessary to understand the exact mechanisms by which metformin acts in horses, and recommend conducting controlled clinical trials.
Cite This Article
APA
Rendle DI, Rutledge F, Hughes KJ, Heller J, Durham AE.
(2013).
Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses.
Equine Vet J, 45(6), 751-754.
https://doi.org/10.1111/evj.12068 Publication
Researcher Affiliations
- The Liphook Equine Hospital, Liphook, UK.
MeSH Terms
- Animals
- Blood Glucose / drug effects
- Cross-Over Studies
- Dexamethasone / pharmacology
- Glucocorticoids / pharmacology
- Glucose / administration & dosage
- Glucose / pharmacology
- Horses
- Hypoglycemic Agents / administration & dosage
- Hypoglycemic Agents / pharmacology
- Insulin / blood
- Insulin / metabolism
- Male
- Metformin / administration & dosage
- Metformin / pharmacology
Citations
This article has been cited 14 times.- Kellon EM, Gustafson KM. Hypertriglyceridemia in equines with refractory hyperinsulinemia treated with SGLT2 inhibitors. Open Vet J 2023 Mar;13(3):365-375.
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- Burns TA, Watts MR, Weber PS, McCutcheon LJ, Geor RJ, Belknap JK. Effect of dietary nonstructural carbohydrate content on activation of 5'-adenosine monophosphate-activated protein kinase in liver, skeletal muscle, and digital laminae of lean and obese ponies. J Vet Intern Med 2014 Jul-Aug;28(4):1280-8.
- 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.
- Palmer AT, Watts MR, Timko KJ, Pinnell EF, Keefer KA, Gorman O, Hostnik LD, Burns TA. Corticosteroid Administration Enhances the Glycemic, Insulinemic, and Incretin Responses to a High-Protein Mixed Meal in Adult Horses. J Vet Intern Med 2025 Mar-Apr;39(2):e17305.
- 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.
- Pinnell EF, Hostnik LD, Watts MR, Timko KJ, Thriffiley AA, Stover MR, Koenig LE, Gorman OM, Toribio RE, Burns TA. Effect of 5'-adenosine monophosphate-activated protein kinase agonists on insulin and glucose dynamics in experimentally induced insulin dysregulation in horses. J Vet Intern Med 2024 Jan-Feb;38(1):102-110.
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