E02 - The Effect of Metformin on the Insulin Response to Oral Sugar in Insulin-dysregulated Horses

Abstract: Background: A single dose of metformin administered 1h prior to oral glucose challenge was previously shown to reduce insulinemic responses in horses with experimentally-induced insulin dysregulation (ID). This effect could be useful for controlling post-prandial hyperinsulinemia in horses with naturally-occurring ID.

Hypothesis/Objectives: The objective was to compare insulinemic and glycemic responses to oral sugar testing (OST) performed at different intervals after a single dose of metformin in horses with naturally-occurring ID. We hypothesized that metformin would significantly decrease the insulinemic response to OST.

Animals: Eight university-owned adult horses with naturally-occurring ID

Methods: In a randomized crossover design, OST was performed 1h, 2h and 6h following a single oral dose of metformin (30 mg/kg) or after placebo (60 ml water) in all horses with a 7-day washout between. Plasma insulin, c-peptide and glucose concentrations were measured at 0, 60 and 90 min after 0.45 ml/kg Karo Light corn syrup and the effect of treatment (and interval since dosing) examined using a mixed effects linear regression model.

Results: Metformin treatment had no significant effect on plasma glucose, insulin or c-peptide concentrations at any time point compared to placebo (p > 0.05). For OST 1h post metformin, median (IQR) plasma insulin was 91.3 uIu/mL (62.4-114.9) at 60 min vs 76.2 uIu/mL (59.1-134.5) for placebo (p = 0.8) and 62.7 uIu/mL (31.4-109.7) at 90 min vs 51.8 uIu/mL (29.2-126.3) for placebo (p = 0.9).

Conclusions and clinical importance: The results do not support the use of targeted metformin treatment to reduce post-prandial hyperinsulinemia in horses with naturally-occurring ID.