Randomized controlled trial assessing the impact of a combined treatment of insulin glargine and propylene glycol on the resolution of hyperketonemia and milk production in postpartum dairy cows

Multiple treatments for hyperketonemia have been studied, and although propylene glycol has been the most constantly reported as successful in mitigating the effects of this condition, a recent study showed that a subpopulation of cows affected by hyperketonemia and hypoglycemia could benefit from a combined treatment of propylene glycol and insulin glargine. The objective of the present study was to assess the effect of this combination on the time-to-hyperketonemia resolution, and on milk production following the initial treatment. A randomized controlled trial was conducted on 2 commercial farms on which postpartum exams were conducted twice a week. Cows naturally affected by both hyperketonemia [β-hydroxybutyrate (BHB) ≥ 1.4 mmol/L] and hypoglycemia (glucose <2.2 mmol/L) were enrolled and randomly assigned to receive 2 mL of placebo (physiological saline) subcutaneously (PBO), or to receive 2 mL of insulin glargine (200 IU) subcutaneously (INS). Cows in both groups also received 300 g of propylene glycol orally for 3 d. Time-to-hyperketonemia resolution (return to BHB <1.4 mmol/L) and daily milk production following the initial treatment were compared between groups using Cox proportional hazard and mixed linear regression models, respectively. A total of 248 cows between 1 and 30 d in milk (median = 16) were enrolled in the trial from January 2018 to February 2022. Cows were of first (32.3%; n = 80/248), second (32.3%; n = 80/248), or third or greater (35.4%; n = 88/248) parity. The overall time-to-hyperketonemia resolution was not different between treatments, but there was a 2-way interaction between treatment group and parity. Primiparous cows had a shorter time-to-resolution in the INS group than in the PBO group; no difference was observed between treatment groups for older cows. The overall milk production of cows in the INS group was 3.4 kg higher than cows in the PBO group during the 14 d after enrollment. There was a 2-way interaction between treatment group and parity. Primiparous cows in the INS group produced 5.3 kg more milk daily than primiparous cows in the PBO group; no effect of treatment was found for older cows. These results suggest that cows affected simultaneously by hyperketonemia and hypoglycemia benefited from a combined treatment of propylene glycol and insulin glargine to improve subsequent milk production and that the effect primarily came from the positive effect in primiparous cows. Time-to-hyperketonemia resolution was also improved in primiparous cows but not in older cows.