Velagliflozin Wins First Equine ID Licence: Hard Endpoint Strength Meets Small-N Fragility

Boehringer Ingelheim Launches First Licensed Equine Insulin Dysregulation Treatment

Boehringer Ingelheim has announced the availability in Great Britain of the first licensed treatment for equine insulin dysregulation, the most common underlying cause of laminitis, which is the leading cause of euthanasia in UK horses. This oral, once-daily therapy, developed over 14 years, demonstrated significant efficacy in a clinical study where no treated ponies developed clinical laminitis, compared to 38% of untreated ponies. The treatment offers a new approach for high-risk horses whose condition cannot be managed by diet and exercise alone, providing vets with a powerful new option to target the primary cause of most laminitis cases.

• Laminitis is a devastating condition affecting one in ten horses and ponies annually in Great Britain, with 90% of cases linked to insulin dysregulation. It is the leading cause of equine euthanasia in the UK, accounting for one in four cases, and one in three affected horses are euthanized within 12 months of diagnosis.
• The newly available oral, once-daily treatment is the first licensed therapy specifically developed for equine insulin dysregulation. It provides a crucial intervention for horses and ponies at high risk of laminitis whose insulin levels cannot be adequately controlled through traditional diet and exercise management alone.
• The treatment's efficacy was demonstrated in a clinical study where 0% of treated ponies developed clinical laminitis, significantly outperforming the 38% incidence rate in untreated ponies. This outcome is the result of over 14 years of dedicated horse-specific research and 19 comprehensive studies.

Addressing the Critical Unmet Need in Equine Insulin Dysregulation

Current treatment approaches for equine insulin dysregulation (ID) face a range of diagnostic, pharmacological, and monitoring challenges that limit optimal clinical outcomes. The complexity of the condition — spanning dynamic testing limitations, drug side effects, and poor real-world compliance — underscores the significant unmet need in this therapeutic area.

• Diagnostic limitations of dynamic testing: The oral sugar test (OST), the preferred dynamic test for ID, presents limitations due to low sensitivity and poor repeatability. Basal insulin remains the simplest accessible method but is influenced by multiple variables including diet, age, stress, season, medications administered, and testing protocols, all of which can confound results.

• Refractory hyperinsulinemia and SGLT2 inhibitor side effects: SGLT2 inhibitors are being used off-label to treat horses with refractory hyperinsulinemia — cases no longer responsive to metformin — but hypertriglyceridemia has emerged as a potential side effect. A cohort study of 20 equines on SGLT2 inhibitors revealed varying degrees of hypertriglyceridemia across animals, with one index case developing hyperlipemia requiring hospitalization and discontinuation of canagliflozin.

• Pergolide does not address insulin dysregulation: In horses with concurrent pituitary pars intermedia dysfunction (PPID) and ID, pergolide treatment lowers basal adrenocorticotropic hormone (ACTH) concentrations but measures of insulin dysregulation are not altered in most cases, leaving a critical therapeutic gap.

• Dietary management constraints: Dietary restriction — including caloric restriction, strict control of non-structural carbohydrates (NSCs), elimination of grains and sweet feeds, and restricted pasture access — is a cornerstone of ID management. However, improvements in insulin sensitivity are dependent on the degree of insulin resistance at outset and the extent of body mass and body condition score losses, making outcomes variable across individuals.

• Poor monitoring compliance in practice: A clinical audit found that only 77.7% (n = 160/206) of pergolide-treated animals had documented PPID monitoring, and of these, only 48.1% (n = 77/160) had follow-up basal ACTH testing in the first 1–3 months following diagnosis — falling below contemporaneous recommendations. Evidence on whether monitoring ACTH concentrations and titrating doses accordingly improves endocrinological or clinical outcome remains unknown.

• Absence of validated biomarkers for early detection: Plasma activin A concentration was investigated as a potential marker for ID and laminitis risk but was found not to be a useful marker. Mass spectrometry-based proteomics has identified proteins in the complement system, coagulation cascade, and extracellular matrix remodelling pathways as altered in equine metabolic syndrome, with several nominated as potential biomarkers for early detection, though these remain investigational.

The Clinical Evidence Supporting SCOVELLA's Approval

Three recent studies have examined interventions for equine insulin dysregulation, each evaluating distinct therapeutic approaches with documented safety and efficacy outcomes.

The study "Use of the SGLT2 inhibitor canagliflozin for control of refractory equine hyperinsulinemia and laminitis" (2022) evaluated canagliflozin (Invokana), administered orally once daily with food, in ten horses with hyperinsulinemia refractory to diet control, metformin, levothyroxine, and pergolide. All ten horses responded with a substantial decrease in serum insulin concentrations to normal or near-normal values. Laminitis pain resolved in all cases, with regression of fat deposits, and owner satisfaction with outcomes was 100%. The authors noted that canagliflozin corrected hyperglycemia and was 100% effective in reversing or reducing abnormal fat pads and eliminating laminitis pain, while recommending that core aspects of therapy — diet control, exercise when possible, and adequate treatment of pituitary pars intermedia dysfunction — must also be maintained.

"The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies" (2019) assessed velagliflozin at 0.3 mg/kg bodyweight orally once daily versus placebo in 24 insulin dysregulated ponies over 16 weeks, with a 4-week withdrawal period. Velagliflozin was well accepted by all subjects and caused no adverse effects or hypoglycaemia. Post-prandial serum insulin concentrations fell from 205 ± 25 μIU/mL at week 0 to 119 ± 19 μIU/mL (P = 0.015) at week 8 and 117 ± 15 μIU/mL (P = 0.029) at week 16, with all 12 treated ponies falling below the previously determined laminitis risk threshold at week 16 (P = 0.003 versus controls). Following 4 weeks of withdrawal, insulin concentrations returned to 199 ± 36 μIU/mL in the treated group, with no rebound effect, indicating that the treatment's benefits were not sustained after discontinuation. The authors concluded that velagliflozin "appears to be a promising and safe treatment for equine insulin dysregulation, bringing post-prandial insulin concentrations below the laminitis risk threshold, albeit without normalising them."

Integrating SCOVELLA into Equine Laminitis Management

The current standard of care for equine insulin dysregulation (ID) centres on dietary restriction and exercise as the primary interventions. Dietary management involves feeding grass hay restricted to 1.25% of body weight as daily dry matter intake, with hay soaked in cold water prior to feeding — a practice shown to produce a significant reduction in non-structural carbohydrates (38%, P = 0.01) and digestible energy (6.78%, P = 0.01). Individually tailored diet and exercise programmes implemented under veterinary guidance have demonstrated significant reductions in body condition score (P<0.001) and bodyweight (P<0.001), accompanied by significant (P<0.05) reductions in basal insulin and improvements in insulin sensitivity. The addition of low-intensity exercise five days per week to dietary restriction produced significantly improved insulin sensitivity and decreased serum amyloid A concentrations relative to dietary restriction alone (both P = .01), supporting the inclusion of exercise as a component of the management programme.

Nutraceutical and pharmacological adjuncts have been investigated where dietary and exercise measures are insufficient. A vitamin and mineral nutraceutical supplement combined with dietary restriction produced an average 6.8% body mass loss and improvements in insulin sensitivity over six weeks, with the magnitude of improvement associated with the degree of insulin resistance at outset and the extent of body mass and body condition score losses. Supplementation with a synergistic polyphenol and amino acid blend including leucine (SPB+L) resulted in significantly lower insulin concentrations at 60- and 75-minute time points and significantly higher baseline high-molecular-weight adiponectin concentrations (P < .05) after six weeks. In contrast, a single oral dose of metformin (30 mg/kg) had no significant effect on plasma glucose, insulin, or C-peptide concentrations at any time point compared with placebo (p > 0.05), and the results do not support the use of targeted metformin treatment to reduce post-prandial hyperinsulinaemia in horses with naturally-occurring ID.

For cases refractory to dietary and nutraceutical management, sodium-glucose cotransporter 2 inhibitors (SGLT2i) — including canagliflozin, ertugliflozin, and velagliflozin — have been used off-label, as there are no licensed veterinary drugs available for treating ID and preventing insulin-associated laminitis in horses. SGLT2i increase urinary glucose excretion by suppressing glucose reabsorption from the glomerular filtrate, resulting in urinary calorie loss with consequent weight loss and improvements in ID. Treatment with ertugliflozin has been shown to decrease resting glucose and insulin concentrations following intra-articular corticosteroid administration, with resting insulin concentrations significantly lower at 12 h, 24 h, 48 h, and 72 h post-injection. However, hypertriglyceridaemia has been identified as a potential side effect of SGLT2i therapy, and further study of this risk, as well as the effect of SGLT2i on circulating adipokine concentrations in horses, is indicated. Doses used are largely extrapolated from human studies with limited consideration of species-specific variations.

A New Era for Equine Laminitis Management

The availability of the first licensed treatment for equine insulin dysregulation represents a pivotal moment in equine health, offering a new frontier in the fight against laminitis. This debilitating hoof disease, often the leading cause of euthanasia, has long presented a significant challenge for veterinarians and horse owners, with management primarily focused on dietary adjustments and symptomatic relief. The new oral, once-daily therapy, an SGLT2 inhibitor, directly targets the underlying hyperinsulinemia that drives endocrinopathic laminitis, moving beyond reactive care to a proactive, causal approach.

This therapeutic innovation holds several key implications for the equine veterinary landscape:

• Redefining Treatment Paradigms: It establishes a new standard for managing insulin dysregulation, potentially shifting the focus towards earlier diagnosis and intervention to prevent laminitis onset.

• Expanding SGLT2 Inhibitor Utility: The success of this class in horses validates its broader application in metabolic disorders, potentially spurring further research into similar conditions in other animal species.

• Enhanced Animal Welfare: By effectively controlling hyperinsulinemia, the treatment promises to significantly reduce the incidence and severity of laminitis, improving the quality of life for countless horses.

However, as with any new therapy, important considerations remain. Studies indicate that while highly effective for most, a subset of horses may not fully respond to SGLT2 inhibitor treatment, underscoring the need for individualized patient assessment. Furthermore, the potential for transient increases in serum triglycerides and, in some cases, hyperlipaemia, highlights the importance of careful monitoring of metabolic parameters during therapy. Crucially, this treatment is not a standalone solution; it complements, rather than replaces, fundamental management strategies such as strict dietary control and appropriate treatment of co-existing conditions like PPID. Integrating this powerful new tool into a comprehensive management plan will be key to maximizing its benefits and ensuring optimal outcomes for horses at risk of laminitis.