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  Discussion on Effects of Metformin on Metabolic SynDrOme
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Moderator:
DrO

Posted on Sunday, Sep 10, 2006 - 1:11 pm:

Though this study was mainly focuses on the reproductive effects of Equine Metabolic SynDrOme, which is primarily a type 2 diabetes, it was interesting in that the human insulin sensitizing drug metformin was not effective at ameliorating the effects of the condition.
DrO

Reprod Fertil Dev. 2006;18(6):609-17.
Obesity is associated with altered metabolic and reproductive activity in the mare: effects of metformin on insulin sensitivity and reproductive cyclicity.
Vick MM, Sessions DR, Murphy BA, Kennedy EL, Reedy SE, Fitzgerald BP.
Department of Veterinary Science, Maxwell Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA.

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 circulating concentrations of leptin and insulin, and decreased insulin sensitivity and concentrations of thyroxine compared with feed-restricted mares throughout the experiment. Experiment 2 was designed to investigate the effects of administration of the insulin-sensitising drug metformin hyDrOchloride on insulin sensitivity and the characteristics of the oestrous cycle in obese mares. In a dose-response trial, metformin increased insulin sensitivity after 30 days following administration of 3 g day(-1), but not 6 or 9 g day(-1), compared with controls receiving vehicle only. However, there were no differences in insulin sensitivity or oestrous cycle characteristics between control and metformin-treated groups when the 3 g day(-1) dose was tested for a longer period of 2 months. These results demonstrate that obesity is associated with aberrations in the oestrous cycle and perturbations in several markers of metabolic status. The results also indicate that metformin is not an effective long-term monotherapy for increasing insulin sensitivity in horses at the doses tested. Additional studies are needed to examine possible effects of increasing insulin sensitivity on reproductive activity in obese mares.
New Member:
kmwhite

Posted on Monday, Mar 8, 2010 - 4:48 pm:

Has metformin been proven to be safe and effective in treating equine metabolic synDrOm or insulin resistance in equines?
Moderator:
DrO

Posted on Tuesday, Mar 9, 2010 - 6:05 pm:

Welcome Karen,
Yes there have been some initial studies with metformin in horses but they have been disappointing. Last year a pharmokinetic study was done and found the horse absorbs it poorly from the bowel.
DrO

Am J Vet Res. 2009 May;70(5):665-8.
Pharmacokinetics and bioavailability of metformin in horses.

Hustace JL, Firshman AM, Mata JE.
Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.

OBJECTIVE: To determine pharmacokinetics and oral bioavailability of metformin in healthy horses. ANIMALS: 4 adult horses. PROCEDURES: 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 administration; PO administration resulted in area under the curves of 1.6 +/- 0.4 h.microg/mL in unfed horses and 0.8 +/- 0.2 h.microg/mL in fed horses. Bioavailability was determined to be approximately 7.1 +/- 1.5% in unfed horses and 3.9 +/- 1.0% in fed horses. The maximal concentration following PO administration in unfed horses was 0.4 +/- 0.1 microg/mL with a time at maximal concentration of 0.9 +/- 0.1 hours. In fed horses, maximal concentration was reduced to 0.3 +/- 0.04 microg/mL with a time at maximal concentration at 1.3 +/- 0.3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: The low bioavailability of metformin may explain the reported lack of clinical success in improving insulin sensitivity with metformin treatment in horses. Dosages and dose intervals previously used may have been insufficient to achieve plasma concentrations of drug comparable to the therapeutic range achieved in humans. Therefore, a larger and more frequently administered dose may be required to fully evaluate efficacy of metformin in horses.
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