Pioglitazone does not adequately control hyperinsulinemia but does increase serum adiponectin concentrations in equids with severe insulin dysregulation.

Abstract

OBJECTIVE: To characterize the effects of pioglitazone (2 mg/kg, PO, either q 24 h [PIO-SID] or q 12 h [PIO-BID]) in equids with severe hyperinsulinemia. METHODS: 17 client-owned equids with severe resting hyperinsulinemia (> 100 µIU/mL) were assigned to PIO-SID or PIO-BID in a prospective cohort study with rolling enrollment over an 11-month study period (December 13, 2022, to November 17, 2023). Basal insulin, total and high-molecular-weight adiponectin concentrations, and plasma pioglitazone concentrations were measured over 70 days. Oral sugar tests (OSTs) were performed on days 0 and 28. Results were analyzed via a mixed-effects linear regression model. RESULTS: Mean (95% CI) resting insulin concentrations decreased from day 0 (PIO-SID, 191.2 µIU/mL [10.1 to 372.1 µIU/mL]; PIO-BID, 113.0 µIU/mL [46.9 to 179.2 µIU/mL]) to day 70 (PIO-SID, 183.4 µIU/mL [-44.6 to 411.4 µIU/mL]; PIO-BID, 66.7 µIU/mL [28.8 to 104.5 µIU/mL]) equivocally in both treatment groups; however OST insulin did not change in either. The high-molecular-weight adiponectin increased in PIO-BID between day 0 (3.5 µg/mL [-0.3 to 7.2 µg/mL]) and day 70 (15.0 µg/mL [6.9 to 23.0 µg/mL]), but not in PIO-SID (day 0 = 0.7 µg/mL [0.2 to 1.3 µg/mL]; day 70 = 4.0 µg/mL [-3.0 to 11.1 µg/mL]). Plasma pioglitazone concentrations on day 70 were 291.8 ng/mL (-40.1 to 623.7 ng/mL [PIO SID]) and 739.7 (453.0 to 1,026.3 ng/mL [PIO-BID]). CONCLUSIONS: Pioglitazone did not affect OST insulin and failed to normalize resting insulin. With PO administration every 12 hours, plasma concentrations exceeded the reported human therapeutic threshold (617 ng/mL), and adiponectin significantly increased. CLINICAL RELEVANCE: Although not effective as a sole treatment for severe hyperinsulinemia, pioglitazone increases adiponectin, a potentially beneficial effect that warrants further investigation.