The new drug designed to treat hyperinsulinemia, velagliflozin from Boehringer Ingelheim Vetmedica GmbH, has proven effective in reducing post-meal insulin levels, according to a recent study conducted by Queensland University of Technology. The new drug targets the overproduction of insulin in response to glucose and excretes excess glucose in the urine.

The study “The efficacy and safety of velaglifozin over 16 weeks as a treatment for insulin dysregulation in ponies” was recently conducted as a follow-up to a previous test on the same drug, published by BMC Veterinary Research. Diets high in carbohydrates have been correlated to the cause of laminitis and equine metabolic syndrome (EMS) in horses and ponies. This leads to insulin sensitivity and hyperinsulinemia. In reducing hyperinsulinemia, researchers are hoping to reduce the prevalence of laminitis and EMS.

Velagliflozin is a sodium-glucose linked transport-2 (SGLT-2) inhibitor. It reduces renal glucose reabsorption and promotes the urination of glucose. In humans, it has been shown to decrease excessive insulin secretion in response to hyperglycemia, or high blood sugar.

In this 16-week study, 22 insulin-dysregulated ponies were selected and tested twice daily after meals to obtain insulin and blood glucose levels. The ponies were separated into test and control groups. The test group was administered velagliflozin, while the control group was given a placebo. Initially, ponies were fed 3.8 grams of non-structural carbohydrates per kilogram of body weight. After the meal, their serum insulin levels were gathered and determined which group they were placed into. 

The diet of the ponies then consisted of a challenge diet containing 7.5 grams of non-structural carbohydrates per kilogram of body weight in order to maintain a fat body condition. The ponies’ safety was monitored closely by veterinarians who examined the ponies daily, including measuring their fasting blood glucose, biochemistry and hematology. Twice daily, professionals monitored ponies for instances of clinical signs of laminitis as well. 

At weeks 8 and 16, the ponies were subjected to a 13-hour overnight fast in which their basal blood glucose levels were then collected following the fast. In addition, following the 16-week study, ponies were subjected to a 4-week withdrawal period of velagliflozin. At the end of the 4-week period, the ponies were fasted once again, and blood glucose levels were obtained. 

The results demonstrated that the daily administration of velagliflozin was effective in reducing ponies’ insulin levels. The levels were brought down below the laminitis risk threshold; however, the drug did not normalize the numbers. No adverse effects of the drug were noted. There were no instances of polydipsia nor polyuria, relating to excessive thirst and urination. Signs of clinical laminitis did not occur after withdrawal either. 

Researchers did not find a drastic change in body weight scores for any of the ponies involved in the study. No remarkable changes in blood chemistry were noted either. Leptin concentrations remained steady. There was a concern for possible hypoglycemia due to the excess levels of glucose being secreted; however, no pony in the study displayed data having low blood sugar. 

There was no available medicine to reduce hyperinsulinemia for horses and ponies prior to this study. Treatment is usually prescribed in pasture restriction or a diet low in non-structural carbohydrates, and exercise when physically possible to improve insulin sensitivity. 

Metformin and levothyroxine are also recommended as side treatments, but neither is registered. Studies show conflicting results with their use as well. The study mentions the possibility of creating insulin reducers to decrease insulin secretion, such as incretin receptor antagonists, but these aren’t available yet. 

The researchers involved in the study include A. Meier, M. de Laat, D. Reiche, D. Fitzgerald and M. Sillence. The study was funded by Boehringer Ingelheim Vetmedica, Germany.