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• In non- laminitic horses with ID, minimum recommendations are low- to- moderate intensity exercise (canter to fast canter, ridden or unridden or heart rates of 130–170 beats/min) for >30 min, >5 times per week.
• In previously laminitic horses with recovered and stable hoof lamellae, minimum exercise recommendations are low- intensity exercise on a soft surface (fast trot to canter unridden or heart rates of 110–150 beats/min) for >30 min, >3 times per week, while carefully monitoring for signs of lameness.
Pharmaceutical adjuncts for HAL
In cases where dietary management and increased exercise have failed to improve hyperinsulinaemia in 4–6 weeks or in animals se- verely affected by HAL, medications should be considered to pre- vent unnecessary suffering (Sundra, Kelty, & Rendle, 2023 ; Sundra, Lester, et al., 2023 ). There are currently no drugs registered for horses that specifically target hyperinsulinaemia and human or ex- temporaneous medications should be used in accordance with local prescribing guidelines. Levothyroxine, a synthetic thyroid hormone, increases basal
metabolic rate and results in both weight loss and improved in- sulin sensitivity when administered to obese horses
(Frank,
Buchanan, & Elliott, 2008 ; Frank, Elliott, & Boston, 2008 ; Sommardahl et al., 2005 ). It is typically administered at 0.1 mg/ kg PO SID for 3–6 months, but diet needs to be strictly controlled as the drug may lead to increases in appetite (Durham, 2017 ). Reports have also shown that levothyroxine is safe and well tol- erated even when used for long periods or at very high doses (Bertin et al., 2019 ;Frank, Buchanan, & Elliott, 2008 ; Frank, Elliott, & Boston, 2008 ; Sommardahl et al., 2005 ). When discontinuing the medication, tapering protocols are recommended, such as re- ducing the dose by half (0.05 mg/kg) for 2 weeks and then halving again (0.025 mg/kg) for a further 2 weeks to allow restoration of the thyroid axis (Sommardahl et al., 2005 ). Metformin is an anti- glycaemic medication that is widely used in
human medicine for the treatment of diabetes and to improve insu- lin sensitivity (Cree- Green et al., 2019 ; Herman et al., 2022 ). Studies performed in horses to assess the efficacy of metformin in hyperin- sulinaemic equids have yielded conflicting results, most likely due to its limited bioavailability (Durham et al., 2008 ; Hustace et al., 2009 ; Rendle et al., 2013 ; Tinworth et al., 2012 ). Dose rates of 15–30 mg/kg PO BID have been reported (Durham et al., 2008 ; Rendle et al., 2013 ) and given the relatively short duration of action, it is recommended that metformin is administered 30 min before turnout or feeding to reduce the post- prandial insulinaemic response (Durham, 2017 ). A re- cent study reported that a single dose of metformin (30 mg/kg) did not significantly reduce the glycaemic or insulinaemic response following an oral sugar test (Colmer et al., 2024 ) although these data may not apply to longer- term therapy with the drug. Anecdotally, the use of metformin in primary care practice appears to be waning, largely being replaced by sodium- glucose cotransporter 2 inhibitors (SGLT2i).
SUNDRA ET AL. The use of SGLT2i drugs for the management of hyperinsuli-
naemia in horses has gained popularity with primary care veter- inarians, despite limited published data on efficacy and safety in equids. This class of drug, also known as gliflozins, does appear to be effective in rapidly reducing insulin concentration, both in experimental studies and refractory cases of HAL in a small number of horses (Frank et al., 2023 ; Kellon & Gustafson, 2022 ; Meier et al., 2019 ; Meier, de Laat, et al., 2018 ; Meier, Reiche, et
al., 2018 ;Sundra, Kelty, & Rendle, 2023 ; Sundra, Lester,
et al., 2023 ). In human medicine, SGLT2i have been used for a de- cade in the management of type 2 diabetes, but in recent years, favourable cardiorenal effects have expanded their use beyond the treatment of metabolic disease (Neal, et al., 2017 ; Wanner et al., 2016 ; Wiviott et al., 2019 ; Zinman et al., 2016 ). In humans, this drug class primarily exerts its effects onthe kidneys. Under normal conditions, the SGLT2 receptor at the proximal convoluted tubule is responsible for approximately 90% of glucose reabsorp- tion, and the SGLT1 receptor is responsible for the remaining 10% (Gerich, 2010 ). SGLT2 inhibitors, as the name suggests, block this glucose reabsorption, leading to an increase in urinary glucose output, a lowering in blood glucose concentration, and therefore a reduction in insulin production in the pancreas (Gerich, 2010 ). It is reported in human studies that the difference in pharmacological effects and outcomes between SGLT2i might be due to the de- gree of SGLT2 receptor selectivity (Memon et al., 2022 ; Schmidt et al., 2021 ) The density and distribution of SGLT1 and 2 receptors in the kidney of equids has not been described but given analo- gous effects on glucose and insulin across species it is likely sim- ilar. However, the exact mechanism by which SGLT2i exert their effects in horses has yet to be elucidated. There are now studies reporting the use of three SGLT2i in horses:
velagliflozin, canagliflozin and ertugliflozin (Frank et al., 2023 ; Kellon & Gustafson, 2022 ; Meier et al., 2019 ; Meier, de Laat, et al., 2018 ; Meier, Reiche, et al., 2018 ;Sundra, Kelty, & Rendle, 2023 ; Sundra, Lester, et al., 2023 ). Velagliflozin has been reported to reduce hy- perinsulinaemia and prevent the development of HAL in experi- mental models where ponies were fed diets high in non- structural carbohydrates (Meier et al., 2019 ; Meier, de Laat, et al., 2018 ; Meier, Reiche, et al., 2018 ). A recent study also demonstrated that velagli- flozin administered at 0.3 mg/kg PO SID was effective in reducing plasma insulin concentrations in horses and ponies with moderate to severe ID (Frank et al., 2023 ). At the time of writing velagliflozin is not commercially available. Experimentally, canagliflozin (admin- istered at 0.6–3.6 mg/kg PO SID) has been reported to reduce the insulin response to an OST (Frank, 2018 ; Lindåse et al., 2023 ) and a small clinical case series demonstrated that it was effective in pro- moting recovery in horses with HAL (Kellon & Gustafson, 2022 ). A case series of 51 horses reported that ertugliflozin (administered at 0.05 mg/kg PO SID) was effective at rapidly reducing insulin con- centration and improving the recovery of clinical cases of HAL that were refractory to diet and management changes (Sundra, Kelty, & Rendle, 2023 ; Sundra, Lester, et al., 2023 ). While these initial results are promising and suggest that SGLT2i are effective in the
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