The Equine Cushing’s and Insulin Resistance (ECIR) Group Inc. announced that Johan Bröjer, DVM, MSc, PhD, Dipl. ACVIM (LAIM), Dipl. ECEIM, Professor of Equine Internal Medicine at Swedish University of Agricultural Sciences has been awarded the inaugural 2024 ECIR research grant.
The one-year project is designed to understand why some horses treated with a new class of drugs that lower insulin develop abnormally high triglycerides.
The use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) are currently the most efficient drugs to control hyperinsulinemia in horses who remain refractory to control of insulin through diet and exercise, but there is limited knowledge of the risk factors associated. An increase in blood triglycerides with SGLT2i treatment appears to be an important side effect, one that warrants further investigation. The increase in triglycerides is highly variable in horses treated with SGLT2i, and it is not clear why some horses experience marked increase in triglycerides while others do not.
Bröjer’s research is a randomized clinical trial where horses are treated with the SGLT2i canagliflozin or a placebo.
This newly funded research builds on previous published work of the ECIR Group. Veterinary and research advisors, Eleanor Kellon, VMD, and Kathleen Gustafson, PhD, co-authored scientific reports based on data provided by members of the ECIR Group, first on the use of SGLT2i in refractory hyperinsulinemia and a second report warning of high triglycerides as a side effect.
“Identifying that hypertriglyceridemia was occurring, presumably as a result of the energy crisis caused by urinary glucose loss, has allowed us to develop protocols for maximizing fat utilization, supporting aerobic energy pathways in the face of loss of glucose and likely important intermediates, and provide higher energy from easily fermentable substrates. While this has been largely successful, we still don't know exactly what is going on with the hormone glucagon and whether or not these horses are actually utilizing the mobilized fat well. This is what Bröjer’s study is designed to investigate,” says Kellon.
“During the study we are investigating how canagliflozin affects the balance between the two important hormones, insulin and glucagon, and how the metabolism of fat is changed,” Bröjer explains. “By understanding which factors are responsible for the uncontrolled increase in triglycerides in some horses, veterinarians will be better prepared to prevent these side effects. The SGLT2i are a fantastic tool in the veterinarians’ treatment box, but we need better understanding of the mechanisms of the side effects and how we can prevent them before we can get the full potential of the SGLT2i ability to prevent laminitis in horses.”
