What to know about this new class of drugs for insulin dysregulation.The SGLT2 inhibitors could help prevent laminitis in insulin-dysregulated horses. | iStockLaminitis due to elevated insulin levels (hyperinsulinemia) remains one of the most serious consequences of insulin dysregulation (ID) in horses.1 While careful diet and management form the foundation of prevention and treatment, scientists are studying a class of drugs new to horses called sodium-glucose cotransporter 2 inhibitors (SGLT2i) to help lower insulin levels. Examples include velagliflozin, canagliflozin (Invokana), and ertugliflozin.Horses with equine metabolic syndrome (EMS) have ID, but so can some horses with pituitary pars intermedia dysfunction (PPID) as well as with certain illnesses or drugs such as corticosteroids.1 For this reason scientists are investigating temporary use of SGLT2i around the time of corticosteroid joint (intra-articular, or IA) injections as ID can lead to hyperinsulemia-associated laminitis (HAL).How Do SGLT2 Inhibitors Work?These drugs inhibit glucose reabsorption in the kidneys, which lowers blood glucose and reduces the need for beta cells in the pancreas to release insulin. In horses they also reduce beta-cell responsiveness to glucose and after-meal glucose concentrations.Researchers found that velagliflozin, the first SGLT2i studied in horses, decreased insulin response in ID ponies to a diet high in nonstructural carbohydrates (NSCs). They also found 36% of nontreated ponies developed laminitis, while no treated ponies did. In a study of moderate to severe ID horses, resting insulin levels dropped in two weeks.2Studies of canagliflozin have revealed similar insulin reductions, laminitis improvement, and decreases in fat deposits and body weight. Some of this work involved horses refractory (resistant) to dietary management alone, metformin, and levothyroxine.2 Veterinarians have also widely prescribed the SGLT2i ertugliflozin either as a tablet (Steglatro) or compounded in various oral forms. In a case series of 51 horses, scientists saw insulin drop significantly within 30 days along with improvements in lameness scores, even though horses stayed on the same low-NSC diet. Nearly all also lost weight, with a mean loss of 16 kilograms (6% of body weight). In a recent survey of owners in the U.K. and Australia, giving ertugliflozin to horses with ID led to marked improvements in quality of life and laminitis lameness.2About one-third of ID horses in another study received pergolide or cabergoline for PPID before SGLT2i therapy, suggesting SGLT2i can be used without negative PPID drug interaction and might serve as an adjunctive HAL therapy for PPID horses.2The FDA has not licensed an SGLT2i for horses, but studies are ongoing toward that goal. It recently licensed velagliflozin for cats.Side Effects and Cautious UseDo not give these drugs to avoid management and diet changes. Short- and long-term effects are still being studied in horses, and serious side effects occur in some horses.The most common negative effects of SGLT2i include an increase in triglyceride levels, cholesterol, lipoproteins, and various liver values. In some horses these changes can be serious. In milder cases lethargy and a decreased appetite might be the only signs. In one study about one-third of owners reported adverse effects,1 including excessive drinking, urination, weight loss, and dullness. Owners have also reported intermittent diarrhea.3 These drugs have been used to treat type 2 diabetes in people but have also been linked to muscle lossa risk we also consider in horses.These side effects highlight the importance of close veterinary supervision, lab monitoring, and dietary management when horses are on SGLT2i.Take-Home MessageManaging ID is complex, and while SGLT2i save lives by lowering the risk of insulin-related laminitis, they fall short of a silver bullet. Long-term success depends on effective dietary and management changes.As an equine internal medicine specialist, I am very excited about this drug class and the chance to prevent HAL and other devastating effects of insulin dysregulation. hReferencesRecommendations for the Diagnosis and Management of Equine Metabolic Syndrome (EMS) and Insulin Dysregulation. Equine Endocrinology Group. 2024.Sundra T, Matthews V, et al. SGLT2 inhibitors: Exploring the effects in humans and horses. Equine Vet Educ. 2025;37:216224.Sundra T, Knowles E, et al. Short-term metabolic responses following treatment with dapagliflozin or ertugliflozin in horses with hyperinsulinemia. In: 6th Global Equine Endocrine Symposium. Ocala, Florida.