Metformin is a biguanide medication commonly used in the management of insulin resistance and metabolic disorders in horses, particularly equine metabolic syndrome (EMS). It is believed to enhance insulin sensitivity and reduce glucose production in the liver, thereby aiding in the regulation of blood sugar levels. Metformin is administered to horses to manage conditions that can lead to laminitis, a painful hoof condition associated with metabolic imbalances. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacokinetics, efficacy, and clinical applications of metformin in equine medicine.
Pinnell EF, Hostnik LD, Watts MR, Timko KJ, Thriffiley AA, Stover MR, Koenig LE, Gorman OM, Toribio RE, Burns TA.5'-adenosine monophosphate-activated protein kinase (AMPK) agonists, particularly resveratrol (RES), have not been extensively evaluated for their effect on insulin dysregulation (ID) in horses. Objective: Evaluate the effects of treatment with RES (10 mg/kg PO q12h), metformin (MET; 30 mg/kg PO q12h), and aspirin (ASP; 20 mg/kg PO q24h) on experimentally induced ID. Methods: Thirty-three healthy, adult, light-breed horses. Methods: Unblinded, placebo-controlled, experimental trial evaluating effects of AMPK agonists (RES, MET, and ASP) on experimentally induced ID. Horses were randomly ...
Kellon EM, Gustafson KM.Sodium-Glucose CoTransporter-2 (SGLT2) inhibitors, the -flozin group of drugs, which block glucose reuptake in the renal proximal tubule, are being increasingly used off-label to treat horses with refractory hyperinsulinemia. After 2 years of use by animals in our group, a horse on canagliflozin was incidentally noted to be hyperlipemic. We have been following a cohort of equines (n = 20) treated with SGLT2 inhibitors due to refractory hyperinsulinemia. The animals are owned by members of the Equine Cushing's and Insulin Resistance Group and treated by their attending veterinarians. The index ...
Ericsson AC, Johnson PJ, Gieche LM, Zobrist C, Bucy K, Townsend KS, Martin LM, LaCarrubba AM.Common treatments for Equine Metabolic Syndrome (EMS) and associated conditions include removal from pasture and adoption of an all-hay diet. Pharmacological treatments for EMS include metformin, a biguanide antihyperglycemic agent also administered to people to help improve glucose tolerance and insulin sensitivity. Both treatments may work, at least partially, through the gut microbiota, yet little is known regarding these effects in the equine host. To determine the influence on the fecal microbiota of this diet change and administration of metformin, six healthy horses were removed from pa...
Smieszek A, Kornicka K, Szłapka-Kosarzewska J, Androvic P, Valihrach L, Langerova L, Rohlova E, Kubista M, Marycz K.In this study, we investigated the influence of metformin (MF) on proliferation and viability of adipose-derived stromal cells isolated from horses (EqASCs). We determined the effect of metformin on cell metabolism in terms of mitochondrial metabolism and oxidative status. Our purpose was to evaluate the metformin effect on cells derived from healthy horses (EqASC) and individuals affected by equine metabolic syndrome (EqASC). The cells were treated with 0.5 μM MF for 72 h. The proliferative activity was evaluated based on the measurement of BrdU incorporation during DNA synthesis, as well as...
Cárceles-Rodríguez CM, Fernández-Varón E, Martín-Gimenez T, Aguirre C, Arion A, Rodríguez MJ, Ayala I.Insulin dysregulation (ID) is a common metabolic disorder in horses. Recently, incretin hormone release has been suggested to be involved in ID in horses. In human medicine, metformin and sitagliptin are commonly used in combination for metabolic syndrome. This combination could be useful in treating ID in horses. However, no pharmacokinetics data have been reported in this species. The objective of the present study was to establish the plasma concentration-time profile and to derive pharmacokinetics data for a combination of metformin and sitagliptin in horses after enteral administration. S...
Durham AE.Equine endocrine disease is commonly encountered by equine practitioners. Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) predominate. The most logical therapeutic approach in PPID uses dopamine agonists; pergolide mesylate is the most common. Bromocryptine and cabergoline are alternative drugs with similar actions. Drugs from other classes have a poor evidence basis, although cyproheptadine and trilostane might be considered. EMS requires management changes as the primary approach; reasonable justification for use of drugs such as levothyroxine and metformin m...
Rendle DI, Rutledge F, Hughes KJ, Heller J, Durham AE.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 ...
Tinworth KD, Edwards S, Noble GK, Harris PA, Sillence MN, Hackett LP.To determine pharmacokinetics and plasma steady-state kinetics of metformin after oral or nasogastric administration in insulin-resistant (IR) ponies. Methods: 8 IR ponies. Methods: Metformin (30 mg/kg) was administered to 8 ponies via nasogastric tube Blood samples were collected at intervals for 24 hours. Plasma concentrations of metformin were measured via liquid chromatography-electrospray tandem mass spectroscopy Pharmacokinetic variables were determined via noncompartmental analysis. Metformin (15 mg/kg, PO, twice daily [8 am and 5 pm]) was administered to 4 ponies for an additional 20 d...
Durham AE, Hughes KJ, Cottle HJ, Rendle DI, Boston RC.Type 2 diabetes mellitus (T2DM) is diagnosed rarely in equine practice although it may be under-recognised. A greater awareness of the condition and therapeutic considerations would be to the benefit of such cases presenting in practice. More investigation into the pharmacological management of these cases is needed. Objective: Three cases of diabetes mellitus were investigated using a specific test for insulin sensitivity and pancreatic beta cell function in order to define accurately and characterise the existence of T2DM in all 3 subjects. Methods: The insulin-modified frequently sampled i....
Hustace JL, Firshman AM, Mata JE.To determine pharmacokinetics and oral bioavailability of metformin in healthy horses. Methods: 4 adult horses. Methods: 6 g of metformin was administered 3 times IV and PO (fed and unfed) to each horse, by use of a crossover design, with a 1-week washout period between treatments. Plasma metformin concentration was determined via high-pressure liquid chromatography. Results: Mean +/- SD distribution half-life of metformin following IV administration was 24.9 +/- 0.4 minutes with a volume of distribution of 0.3 +/- 0.1 L/kg. Mean area under the curve was 20.9 +/- 2.0 h.microg/mL for IV adminis...
Durham AE, Rendle DI, Newton JE.Laminitis in equids is a very common debilitating disease, and insulin resistance (IR) and hyperinsulinaemia are increasingly recognised as important predisposing factors. Pharmacological modification of IR and hyperinsulinaemia might reduce the risk of laminitis. Objective: Metformin, a drug commonly prescribed for treatment of human IR, may also decrease IR in equids. Methods: Eighteen horses and ponies with IR and recurrent laminitis were treated with 15 mg/kg bwt metformin per os q. 12 h. Each animal served as its own control by comparing pre- and post treatment proxies for IR, insulin sen...
Vick MM, Sessions DR, Murphy BA, Kennedy EL, Reedy SE, Fitzgerald BP.In mares, obesity is associated with continuous reproductive activity during the non-breeding season. To investigate the effect of obesity and associated alterations in metabolic parameters on the oestrous cycle, two related studies were conducted. In Experiment 1, obese (body condition score > 7) mares were fed ad libitum or were moderately feed restricted during the late summer and autumn months. Feed restriction did not alter the proportion of mares entering seasonal anoestrus. However, obese mares exhibited a significantly longer duration of the oestrous cycle, significant increases in ...
Johnson PJ, Scotty NC, Wiedmeyer C, Messer NT, Kreeger JM.An 18-year-old Spanish Mustang mare was referred for evaluation of progressive weight loss and persistent hyperglycemia. Clinicopathologic abnormalities included marked hyperglycemia and glycosuria. Serum cortisol concentration was appropriately decreased following administration of dexamethasone, indicating that the horse did not have pituitary pars intermedia dysfunction. Serum insulin and plasma C-peptide concentrations were low, suggesting that hyperglycemia was a result of decreased secretion of insulin by pancreatic beta cells. In addition, glucose concentration did not return to the bas...
Vick MM, Sessions DR, Murphy BA, Kennedy EL, Reedy SE, Fitzgerald BP.In mares, obesity is associated with continuous reproductive activity during the non-breeding season. To investigate the effect of obesity and associated alterations in metabolic parameters on the oestrous cycle, two related studies were conducted. In Experiment 1, obese (body condition score > 7) mares were fed ad libitum or were moderately feed restricted during the late summer and autumn months. Feed restriction did not alter the proportion of mares entering seasonal anoestrus. However, obese mares exhibited a significantly longer duration of the oestrous cycle, significant increases in ...
Smieszek A, Kornicka K, Szłapka-Kosarzewska J, Androvic P, Valihrach L, Langerova L, Rohlova E, Kubista M, Marycz K.In this study, we investigated the influence of metformin (MF) on proliferation and viability of adipose-derived stromal cells isolated from horses (EqASCs). We determined the effect of metformin on cell metabolism in terms of mitochondrial metabolism and oxidative status. Our purpose was to evaluate the metformin effect on cells derived from healthy horses (EqASC) and individuals affected by equine metabolic syndrome (EqASC). The cells were treated with 0.5 μM MF for 72 h. The proliferative activity was evaluated based on the measurement of BrdU incorporation during DNA synthesis, as well as...
Rendle DI, Rutledge F, Hughes KJ, Heller J, Durham AE.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 ...
Durham AE, Rendle DI, Newton JE.Laminitis in equids is a very common debilitating disease, and insulin resistance (IR) and hyperinsulinaemia are increasingly recognised as important predisposing factors. Pharmacological modification of IR and hyperinsulinaemia might reduce the risk of laminitis. Objective: Metformin, a drug commonly prescribed for treatment of human IR, may also decrease IR in equids. Methods: Eighteen horses and ponies with IR and recurrent laminitis were treated with 15 mg/kg bwt metformin per os q. 12 h. Each animal served as its own control by comparing pre- and post treatment proxies for IR, insulin sen...
Hustace JL, Firshman AM, Mata JE.To determine pharmacokinetics and oral bioavailability of metformin in healthy horses. Methods: 4 adult horses. Methods: 6 g of metformin was administered 3 times IV and PO (fed and unfed) to each horse, by use of a crossover design, with a 1-week washout period between treatments. Plasma metformin concentration was determined via high-pressure liquid chromatography. Results: Mean +/- SD distribution half-life of metformin following IV administration was 24.9 +/- 0.4 minutes with a volume of distribution of 0.3 +/- 0.1 L/kg. Mean area under the curve was 20.9 +/- 2.0 h.microg/mL for IV adminis...
Durham AE, Hughes KJ, Cottle HJ, Rendle DI, Boston RC.Type 2 diabetes mellitus (T2DM) is diagnosed rarely in equine practice although it may be under-recognised. A greater awareness of the condition and therapeutic considerations would be to the benefit of such cases presenting in practice. More investigation into the pharmacological management of these cases is needed. Objective: Three cases of diabetes mellitus were investigated using a specific test for insulin sensitivity and pancreatic beta cell function in order to define accurately and characterise the existence of T2DM in all 3 subjects. Methods: The insulin-modified frequently sampled i....
Durham AE.Equine endocrine disease is commonly encountered by equine practitioners. Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) predominate. The most logical therapeutic approach in PPID uses dopamine agonists; pergolide mesylate is the most common. Bromocryptine and cabergoline are alternative drugs with similar actions. Drugs from other classes have a poor evidence basis, although cyproheptadine and trilostane might be considered. EMS requires management changes as the primary approach; reasonable justification for use of drugs such as levothyroxine and metformin m...
Johnson PJ, Scotty NC, Wiedmeyer C, Messer NT, Kreeger JM.An 18-year-old Spanish Mustang mare was referred for evaluation of progressive weight loss and persistent hyperglycemia. Clinicopathologic abnormalities included marked hyperglycemia and glycosuria. Serum cortisol concentration was appropriately decreased following administration of dexamethasone, indicating that the horse did not have pituitary pars intermedia dysfunction. Serum insulin and plasma C-peptide concentrations were low, suggesting that hyperglycemia was a result of decreased secretion of insulin by pancreatic beta cells. In addition, glucose concentration did not return to the bas...
Tinworth KD, Edwards S, Noble GK, Harris PA, Sillence MN, Hackett LP.To determine pharmacokinetics and plasma steady-state kinetics of metformin after oral or nasogastric administration in insulin-resistant (IR) ponies. Methods: 8 IR ponies. Methods: Metformin (30 mg/kg) was administered to 8 ponies via nasogastric tube Blood samples were collected at intervals for 24 hours. Plasma concentrations of metformin were measured via liquid chromatography-electrospray tandem mass spectroscopy Pharmacokinetic variables were determined via noncompartmental analysis. Metformin (15 mg/kg, PO, twice daily [8 am and 5 pm]) was administered to 4 ponies for an additional 20 d...
Kellon EM, Gustafson KM.Sodium-Glucose CoTransporter-2 (SGLT2) inhibitors, the -flozin group of drugs, which block glucose reuptake in the renal proximal tubule, are being increasingly used off-label to treat horses with refractory hyperinsulinemia. After 2 years of use by animals in our group, a horse on canagliflozin was incidentally noted to be hyperlipemic. We have been following a cohort of equines (n = 20) treated with SGLT2 inhibitors due to refractory hyperinsulinemia. The animals are owned by members of the Equine Cushing's and Insulin Resistance Group and treated by their attending veterinarians. The index ...
Ericsson AC, Johnson PJ, Gieche LM, Zobrist C, Bucy K, Townsend KS, Martin LM, LaCarrubba AM.Common treatments for Equine Metabolic Syndrome (EMS) and associated conditions include removal from pasture and adoption of an all-hay diet. Pharmacological treatments for EMS include metformin, a biguanide antihyperglycemic agent also administered to people to help improve glucose tolerance and insulin sensitivity. Both treatments may work, at least partially, through the gut microbiota, yet little is known regarding these effects in the equine host. To determine the influence on the fecal microbiota of this diet change and administration of metformin, six healthy horses were removed from pa...
Cárceles-Rodríguez CM, Fernández-Varón E, Martín-Gimenez T, Aguirre C, Arion A, Rodríguez MJ, Ayala I.Insulin dysregulation (ID) is a common metabolic disorder in horses. Recently, incretin hormone release has been suggested to be involved in ID in horses. In human medicine, metformin and sitagliptin are commonly used in combination for metabolic syndrome. This combination could be useful in treating ID in horses. However, no pharmacokinetics data have been reported in this species. The objective of the present study was to establish the plasma concentration-time profile and to derive pharmacokinetics data for a combination of metformin and sitagliptin in horses after enteral administration. S...
Pinnell EF, Hostnik LD, Watts MR, Timko KJ, Thriffiley AA, Stover MR, Koenig LE, Gorman OM, Toribio RE, Burns TA.5'-adenosine monophosphate-activated protein kinase (AMPK) agonists, particularly resveratrol (RES), have not been extensively evaluated for their effect on insulin dysregulation (ID) in horses. Objective: Evaluate the effects of treatment with RES (10 mg/kg PO q12h), metformin (MET; 30 mg/kg PO q12h), and aspirin (ASP; 20 mg/kg PO q24h) on experimentally induced ID. Methods: Thirty-three healthy, adult, light-breed horses. Methods: Unblinded, placebo-controlled, experimental trial evaluating effects of AMPK agonists (RES, MET, and ASP) on experimentally induced ID. Horses were randomly ...
