The effect of pre‐dosing with metformin on the insulin response to oral sugar in insulin‐dysregulated horses

Abstract

AbstractBackgroundA single dose of metformin administered 1 h prior to oral glucose challenge was previously shown to reduce insulinaemic responses in horses with experimentally‐induced insulin dysregulation (ID). Targeted administration could be useful for controlling post‐prandial hyperinsulinaemia in horses with naturally‐occurring ID.ObjectivesThe objective was to compare the insulinaemic and glycaemic responses to oral sugar testing (OST) performed at different intervals after a single dose of metformin in horses with naturally‐occurring ID. We hypothesised that pre‐treatment with one dose of metformin would significantly decrease the insulinaemic response to OST.Study designRandomised cross‐over in vivo experiment.MethodsEight university‐owned adult horses with naturally‐occurring ID underwent OST 1, 2 and 6 h following a single oral dose of metformin (30 mg/kg) or 1 h after placebo (240 mL water) with a 7‐day washout between treatments over a period of 3 weeks. Plasma insulin, C‐peptide and glucose concentrations were measured at 0, 60 and 90 min after 0.45 mL/kg light corn syrup and the effect of treatment (and the interval since dosing) examined using a mixed effects linear regression model.ResultsMetformin treatment had no significant effect on plasma glucose, insulin or C‐peptide concentrations at any time point compared with placebo (p > 0.05). For OST 1 h post metformin, median (IQR) plasma insulin was 91.3 (62.4–114.9) μIU/mL at 60 min versus 76.2 (59.1–134.5) for placebo (p = 0.8) and 62.7 (31.4–109.7) at 90 min versus 51.8 (29.2–126.3) for placebo (p = 0.9).Main limitationsSmall sample size may limit identification of more subtle decreases in insulin concentration with metformin pre‐dosing. The results of this study are relevant only for one pre‐treatment dose (30 mg/kg) which limits extrapolation to predictions about the effects of longer‐term metformin administration on insulin and glucose dynamics in the horse.Conclusions and clinical importanceThe results do not support the use of targeted metformin treatment to reduce post‐prandial hyperinsulinaemia in horses with naturally‐occurring ID.