After research, HISA proposes new reporting limit for metformin

The Horseracing Integrity and Safety Authority and Horseracing Integrity & Welfare Unit announced Monday that HISA’s anti-doping and medication control committee has recommended the adoption of a minimum reporting level for the banned substance metformin in the latest version of proposed modifications to the ADMC program rules. The rules will be circulated for public comment in the coming days. The proposed MRL is 4.0 nanograms per milliliter in blood and is based on recommendations received at HISA and HIWU’s request from the Racing Medication & Testing Consortium’s scientific advisory committee.

Pre-HISA, the Association of Racing Commissioners International’s model rules categorized metformin as a prohibited substance, but there was not a published testing specification for it, which meant that reported findings were determined by an individual laboratory’s limit of detection for the substance. As such, enforcement of metformin lacked uniformity and consistency among the states. Once HIWU assumed control of the ADMC Program, the testing specifications for metformin were harmonized based on the capabilities of program laboratories at 0.5 nanograms per milliliter in blood and 1 nanogram per milliliter in urine. This ensured that all laboratories were testing at the same level, thus maintaining fairness for horsemen regardless of where they race.

Following a series of positive test results (adverse analytical findings) for metformin and intelligence received by HIWU that trainers were intentionally administering metformin to covered horses to enhance performance, HISA and HIWU asked the RMTC's SAC to conduct an independent review of the available science relating to metformin in June 2024 to determine if it was appropriate to modify the regulation of this substance. During this period, HIWU stayed the prosecution of all unresolved and new cases involving potential presence violations (i.e., positive tests) for metformin, although there have been zero reported AAFs in 2025 while testing at 0.5 nanograms per milliliter in blood and 1 nanogram per milliliter in urine.

The SAC’s investigation consisted of an initial review of the existing scientific literature followed by a three-part study performed by Dr. Heather Knych with the K.L. Maddy equine analytical chemistry laboratory at the University of California, Davis school of veterinary medicine. The research completed by Dr. Knych and her team has resulted in three manuscripts that have all been submitted for scientific publication, the first of which, “Metformin in the Horse: Pharmacokinetics and Detection Times Using Monte Carlo Simulations," has been accepted for publication in Drug Testing and Analysis. The manuscripts describe the pharmacokinetics (i.e., how the body interacts with a substance) of metformin following a single intravenous and oral administration in the horse, the pharmacokinetics of metformin in various blood matrices including partitioning into equine red blood cells and the potential for detection of metformin in blood and urine samples following a horse’s exposure to metformin-contaminated urine and shavings.

The SAC agreed that an MRL of 4.0 nanograms per milliliter in blood reflects exposure to metformin due to intentional administration and minimizes the possibility of a reported AAF due to inadvertent exposure. Dr. Knych’s administration study determined that metformin demonstrates an erratic elimination behavior in urine and an inconsistent relationship between urine and blood concentrations. Therefore, the SAC recommended that laboratories perform confirmatory analysis in blood only.

“We are thankful to UC Davis, Dr. Knych, and her team for performing groundbreaking research on metformin. HISA and HIWU’s call for this review of metformin aligns with our mandate to utilize science when making regulatory decisions to prioritize safety, integrity, welfare, and fairness,” said HIWU executive director Ben Mosier. “Additionally, we appreciate our ongoing collaboration with the RMTC’s SAC to facilitate these research projects and ultimately enhance the effectiveness of the ADMC Program.”

There are currently nine unresolved, and therefore stayed, presence cases for metformin. They will continue to be stayed pending the Federal Trade Commission’s approval of the new MRL. If approved, this change will not impact cases that were resolved prior to the June 2024 announcement and involved violations of the rules and testing specifications in effect at the time.

Metformin, which has no valid veterinary use in the racehorse, will remain a banned substance. The presence, use, administration, possession, or trafficking of any banned substance is subject to a period of ineligibility of up to two years, a fine of up to $25,000, the disqualification of race results as applicable, and public disclosure. Horsemen are encouraged to maintain best practices for stable hygiene in their training operations to minimize the risk of inadvertent exposure to metformin and other prohibited substances.